Focal Transcranial Magnetic Stimulation Research Articles

Design and evaluation of a rodent-specific focal transcranial magnetic stimulation coil with the custom shielding application in rats.

Repetitive TMS has been used as an alternative treatment for various neurological disorders. However, most TMS mechanism studies in rodents have been based on the whole brain stimulation, the lack of rodent-specific focal TMS coils restricts the proper translation of human TMS protocols to animal models. In this study, we designed a new shielding device, which was made of high magnetic permeability material, to enhance the spatial focus of animal-use TMS coils. With the finite element method, we analyzed the electromagnetic field of the coil with and without the shielding device. Furthermore, to assess the shielding effect in rodents, we compared the c-fos expression, the ALFF and ReHo values in different groups following a 15 min 5 Hz rTMS paradigm. We found that a smaller focality with an identical core stimulation intensity was achieved in the shielding device. The 1 T magnetic field was reduced from 19.1 mm to 13 mm in diameter, and 7.5 to 5.6 mm in depth. However, the core magnetic field over 1.5 T was almost the same. Meanwhile, the area of electric field was reduced from 4.68 cm2 to 4.19 cm2, and 3.8 mm to 2.6 mm in depth. Similar to this biomimetic data, the c-fos expression, the ALFF and ReHo values showed more limited cortex activation with the use of the shielding device. However, compared to the rTMS group without the shielding application, more subcortical regions, like the striatum (CPu), the hippocampus, the thalamus, and the hypothalamus were also activated in the shielding group. This indicated that more deep stimulation may be achieved by the shielding device. Generally, compared with the commercial rodents' TMS coil (15 mm in diameter), TMS coils with the shielding device achieved a better focality (~6 mm in diameter) by reducing at least 30% of the magnetic and electric field. This shielding device may provide a useful tool for further TMS studies in rodents, especially for more specific brain area stimulation.

A C-shaped miniaturized coil for transcranial magnetic stimulation in rodents

Objective. Transcranial magnetic stimulation (TMS) is a non-invasive technique widely used for neuromodulation. Animal models are essential for investigating the underlying mechanisms of TMS. However, the lack of miniaturized coils hinders the TMS studies in small animals, since most commercial coils are designed for humans and thus incapable of focal stimulation in small animals. Furthermore, it is difficult to perform electrophysiological recordings at the TMS focal point using conventional coils. Approach. We designed, fabricated, and tested a novel miniaturized TMS coil (4-by-7 mm) that consisted of a C-shaped iron powder core and insulated copper wires (30 turns). The resulting magnetic and electric fields were characterized with experimental measurements and finite element modeling. The efficacy of this coil in neuromodulation was validated with electrophysiological recordings of single-unit activities (SUAs), somatosensory evoked potentials (SSEPs), and motor evoked potentials (MEPs) in rats (n = 32) following repetitive TMS (rTMS; 3 min, 10 Hz). Main results. This coil could generate a maximum magnetic field of 460 mT and an electric field of 7.2 V m−1 in the rat brain according to our simulations. With subthreshold rTMS focally delivered over the sensorimotor cortex, mean firing rates of primary somatosensory and motor cortical neurons significantly increased (154 5% and 160 9% from the baseline level, respectively); MEP and SSEP amplitude significantly increased (136 9%) and decreased (74 4%), respectively. Significance. This miniaturized C-shaped coil enabled focal TMS and concurrent electrophysiological recording/stimulation at the TMS focal point. It provided a useful tool to investigate the neural responses and underlying mechanisms of TMS in small animal models. Using this paradigm, we for the first time observed distinct modulatory effects on SUAs, SSEPs, and MEPs with the same rTMS protocol in anesthetized rats. These results suggested that multiple neurobiological mechanisms in the sensorimotor pathways were differentially modulated by rTMS.

In vivo low-intensity magnetic pulses durably alter neocortical neuron excitability and spontaneous activity.

Magnetic brain stimulation is a promising treatment for neurological and psychiatric disorders. However, a better understanding of its effects at the individual neuron level is essential to improve its clinical application. We combined focal low-intensity repetitive transcranial magnetic stimulation (LI-rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neurons in vivo. Continuous 10Hz LI-rTMS reliably evoked firing at ∼4-5Hz during the stimulation period and induced durable attenuation of synaptic activity and spontaneous firing in cortical neurons, through membrane hyperpolarization and a reduced intrinsic excitability. However, inducing firing in individual neurons by repeated intracellular current injection did not reproduce the effects of LI-rTMS on neuronal properties. These data provide a novel understanding of mechanisms underlying magnetic brain stimulation showing that, in addition to inducing biochemical plasticity, even weak magnetic fields can activate neurons and enduringly modulate their excitability. KEY POINTS: Repetitive transcranial magnetic stimulation (rTMS) is a promising technique to alleviate neurological and psychiatric disorders caused by alterations in cortical activity. Our knowledge of the cellular mechanisms underlying rTMS-based therapies remains limited. We combined in vivo focal application of low-intensity rTMS (LI-rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neurons to characterize the effects of weak magnetic fields at single cell level. Ten minutes of LI-rTMS delivered at 10Hz reliably evoked action potentials in cortical neurons during the stimulation period, and induced durable attenuation of their intrinsic excitability, synaptic activity and spontaneous firing. These results help us better understand the mechanisms of weak magnetic stimulation and should allow optimizing the effectiveness of stimulation protocols for clinical use.

The effect of meninges on the electric fields in TES and TMS. Numerical modeling with adaptive mesh refinement

BackgroundWhen modeling transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) in the brain, the meninges – dura, arachnoid, and pia mater – are often neglected due to high computational costs. ObjectiveWe investigate the impact of the meningeal layers on the cortical electric field in TES and TMS while considering the headreco segmentation as the base model. MethodWe use T1/T2 MRI data from 16 subjects and apply the boundary element fast multipole method with adaptive mesh refinement, which enables us to accurately solve this problem and establish method convergence at reasonable computational cost. We compare electric fields in the presence and absence of various meninges for two brain areas (M1HAND and DLPFC) and for several distinct TES and TMS setups. ResultsMaximum electric fields in the cortex for focal TES consistently increase by approximately 30% on average when the meninges are present in the CSF volume. Their effect on the maximum field can be emulated by reducing the CSF conductivity from 1.65 S/m to approximately 0.85 S/m. In stark contrast to that, the TMS electric fields in the cortex are only weakly affected by the meningeal layers and slightly (∼6%) decrease on average when the meninges are included. ConclusionOur results quantify the influence of the meninges on the cortical TES and TMS electric fields. Both focal TES and TMS results are very consistent. The focal TES results are also in a good agreement with a prior relevant study. The solver and the mesh generator for the meningeal layers (compatible with SimNIBS) are available online.

Modulation of Interhemispheric Inhibition between Primary Motor Cortices Induced by Manual Motor Imitation: A Transcranial Magnetic Stimulation Study.

Imitation has been proven effective in motor development and neurorehabilitation. However, the relationship between imitation and interhemispheric inhibition (IHI) remains unclear. Transcranial magnetic stimulation (TMS) can be used to investigate IHI. In this study, the modification effects of IHI resulting from mirror neuron system (MNS) activation during different imitations are addressed. We measured IHI between homologous primary motor cortex (M1) by analyzing the ipsilateral silent period (iSP) evoked by single-pulse focal TMS during imitation and analyzed the respective IHI modulation during and after different patterns of imitation. Our main results showed that throughout anatomical imitation, significant time-course changes of iSP duration through the experiment were observed in both directions. iSP duration declined from the pre-imitation time point to the post-imitation time point and did not return to baseline after 30 min rest. We also observed significant iSP reduction from the right hemisphere to the left hemisphere during anatomical and specular imitation, compared with non-imitative movement. Our findings indicate that using anatomical imitation in action observation and execution therapy promotes functional recovery in neurorehabilitation by regulating IHI.

Effects of transcranial magnetic stimulation over the left posterior superior temporal gyrus on picture-word interference.

Word-production theories argue that during language production, a concept activates multiple lexical candidates in left temporal cortex, and the intended word is selected from this set. Evidence for theories on spoken-word production comes, for example, from the picture-word interference task, where participants name pictures superimposed by congruent (e.g., picture: rabbit, distractor "rabbit"), categorically related (e.g., distractor "sheep"), or unrelated (e.g., distractor "fork") words. Typically, whereas congruent distractors facilitate naming, related distractors slow down picture naming relative to unrelated distractors, resulting in semantic interference. However, the neural correlates of semantic interference are debated. Previous neuroimaging studies have shown that the left mid-to-posterior STG (pSTG) is involved in the interference associated with semantically related distractors. To probe the functional relevance of this area, we targeted the left pSTG with focal repetitive transcranial magnetic stimulation (rTMS) while subjects performed a picture-word interference task. Unexpectedly, pSTG stimulation did not affect the semantic interference effect but selectively increased the congruency effect (i.e., faster naming with congruent distractors). The facilitatory TMS effect selectively occurred in the more difficult list with an overall lower name agreement. Our study adds new evidence to the causal role of the left pSTG in the interaction between picture and distractor representations or processing streams, only partly supporting previous neuroimaging studies. Moreover, the observed unexpected condition-specific facilitatory rTMS effect argues for an interaction of the task- or stimulus-induced brain state with the modulatory TMS effect. These issues should be systematically addressed in future rTMS studies on language production.

Anterior and Posterior Left Inferior Frontal Gyrus Contribute to the Implementation of Grammatical Determiners During Language Production

The left inferior frontal gyrus (IFG) is a key region for language comprehension and production. Previous studies point to a preferential involvement of left anterior IFG (aIFG) in lexical and semantic processes, while the posterior IFG (pIFG) has been implicated in supporting syntactic and phonological processes. Here we used focal neuronavigated transcranial magnetic stimulation (TMS) to probe the functional involvement of left IFG in lexical and grammatical processing at the sentence level. We applied 10 Hz TMS effective or sham bursts to left aIFG and pIFG, while healthy volunteers performed an adjective-noun production task contrasting grammatical and lexical determiners. For each trial, we measured the time from the stimulus onset to the moment of articulation (response time) and the time from articulation onset to the end of articulation (duration). Focal TMS of IFG generally delayed response times. The TMS-induced delay in response times was relatively stronger for the grammatical condition compared to the lexical condition, when TMS targeted aIFG. Articulation of the determiner was generally shorter in trials presenting grammatical determiners relative to lexical determiners. The shorter articulation time for grammar determiners was facilitated by effective TMS to pIFG. Together, the effects of TMS on task performance provide novel evidence for a joint involvement of anterior and posterior parts of left IFG in implementing grammatical determiners during language production, suggesting an involvement of aIFG in the initiation and pIFG in the production of grammatically appropriate verbal responses at the sentence level.

Transcranial magnetic stimulation in child neurology

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation used for research and diagnostic purposes, as well as for the treatment of a number of diseases as one of the methods of neuromodulation. In pediatrics, TMS is most often used to assess the normal maturation of the corticospinal tract when stimulating the motor areas of the cortex of healthy children with a short single pulse magnetic stimulus, and recording motor evoked potentials from different muscles of the upper and lower extremities, as well as calculating the central motor conduction time. This technique is also used in pediatric neurology to determine conduction disturbances of the pulse along the corticospinal tract and to test neuroplasticity in damage to motor areas of the cerebral cortex and descending motor pathways in such diseases as cerebral palsy, stroke, and multiple sclerosis. Another aspect of TMS application is the evaluation of cortical inhibitory mechanisms with an assessment of the indices of the cortical silent period and the ipsilateral silent period, which often change with central nervous system lesions. With TMS it is also possible to map the cortical representation of a particular muscle, which is used to evaluate functional changes of the cerebral cortex in various neurological diseases. For an accurate implementation of the TMS mapping technique, complex navigation equipment must be currently used with focal TMS. The article describes in detail these and other diagnostic methods of TMS used in child neurology. The possibilities of the therapeutic use of repetitive TMS in childrens neurological diseases are considered in separate sections.

Focal transcranial magnetic stimulation in awake rats: Enhanced glucose uptake in deep cortical layers

BackgroundTranscranial magnetic stimulation (TMS) is an emerging neuromodulation tool. However, preclinical models of TMS are limited. ObjectiveTo develop a method for performing TMS in awake rats and to characterize neuronal response to TMS by mapping glucose uptake following TMS administration. MethodsA headpost was implanted into rat skull serving as a refence to guide TMS target. Motor threshold measurement was used as the metric to assess the consistency in TMS delivery across animals and across sessions. Using a fluorescent glucose analogue (2-NBDG) as a marker of neuronal activity, we mapped glucose uptake in response to TMS of the rat motor cortex. ResultsThe average motor threshold (n = 41) was 34.6 ± 6.3 % of maximum stimulator output (MSO). The variability of motor threshold across animals was similar to what has been reported in human studies. Furthermore, there was no significant difference in motor threshold measured across 3 separate days. Enhancement in fluorescent signals were TMS dose (power)-dependent, which centered around the motor cortex, covering an area medial-laterally 2 mm, rostral-caudally 4 mm at 55 % MSO, and 3 mm at 35 % MSO. The count of total cells with significant fluorescent signal was: 107 ± 23 (55 % MSO), 73 ± 11 (35 % MSO) and 42 ± 11 (sham, 5% MSO). ConclusionsOur method allows for consistent motor threshold assessment for longitudinal studies. Notably, cells with fluorescent signal enhancement were consistently aggregated in deep cortical layers, with minimal enhancement in superficial layers Comparisons with existing method(s)To our knowledge, this is the first study of focal TMS in awake rodents.

Design and Evaluation of a Rodent-Specific Transcranial Magnetic Stimulation Coil: An In Silico and In Vivo Validation Study

BackgroundRodent models are fundamental in unraveling cellular and molecular mechanisms of transcranial magnetic stimulation (TMS)‐induced effects on the brain. However, proper translation of human TMS protocols to animal models have been restricted by the lack of rodent‐specific focal TMS coils.ObjectiveWe aimed to improve TMS focalization in rodent brain with a novel small, cooled, and rodent‐specific TMS coil.MethodsA rodent‐specific 25‐mm figure‐of‐eight TMS coil was developed. Stimulation focalization was simulated in silico for the rodent coil and a commercial human 50‐mm figure‐of‐eight TMS coil. Both coils were also compared in vivo by electromyography measurements of brachialis motor evoked potential (MEP) responses to TMS at different brain sites in anesthetized rats (n = 6). Focalization was determined from the coils' level of stimulation laterality. Differences in MEPs were statistically analyzed with repeated‐measures, within‐subjects, ANOVA.Results In silico simulation results deemed the human coil insufficient for unilateral stimulation of the rat motor cortex, whereas lateralized electrical field induction was projected attainable with the rodent coil. Cortical, in vivo MEP amplitude measurements from multiple points in each hemisphere, revealed unilateral activation of the contralateral brachialis muscle, in absence of ipsilateral brachialis activation, with both coils.ConclusionComputer simulations motivated the design of a smaller rodent‐specific TMS coil, but came short in explaining the capability of a larger commercial human coil to induce unilateral MEPs in vivo. Lateralized TMS, as demonstrated for both TMS coils, corroborates their use in translational rodent studies, to elucidate mechanisms of action of therapeutic TMS protocols.

P173 Computationally-designed Focal Deep Transcranial Magnetic Stimulation (fdTMS) coils

P173 Computationally-designed Focal Deep Transcranial Magnetic Stimulation (fdTMS) coils

Role of human prefrontal cortex in the modulation of conditioned eyeblink responses

Classical conditioning of the eyeblink reflex (EBC) is a simple form of associative motor learning. EBC is heavily dependent on cerebellar function, but experimental studies also suggest that the prefrontal cortex (PFC) orchestrates a neuronal network which interacts with the cerebellum to mediate the conditioned eyeblink responses (CR).To further investigate the role of PFC for EBC in humans, we aimed in this study at assessing whether acquisition of CR can be modulated by focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the dorsolateral PFC (DLPFC).A standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 60 healthy subjects (35 female, 25 male, mean age 28.4 ± 2.4 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. TBS was applied over the DLPFC ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 20) using excitatory intermittent TBS (iTBS), inhibitory continuous TBS (cTBS) or sham stimulation.CR acquisition was significantly enhanced by iTBS (mean total CR incidence 63.1 ± 6.5%) and significantly reduced by cTBS (13 ± 2%) compared to sham stimulation (25.1 ± 6.7%).We provide thus physiological evidence that the acquisition of this type of associative learning is critically modulated by PFC activity in humans.

Can Transcranial Electrical Stimulation Localize Brain Function?

Transcranial electrical stimulation (TES) uses constant (TDCS) or alternating currents (TACS) to modulate brain activity. Most TES studies apply low-intensity currents through scalp electrodes (≤2 mA) using bipolar electrode arrangements, producing weak electrical fields in the brain (<1 V/m). Low-intensity TES has been employed in humans to induce changes in task performance during or after stimulation. In analogy to focal transcranial magnetic stimulation, TES-induced behavioral effects have often been taken as evidence for a causal involvement of the brain region underlying one of the two stimulation electrodes, often referred to as the active electrode. Here, we critically review the utility of bipolar low-intensity TES to localize human brain function. We summarize physiological substrates that constitute peripheral targets for TES and may mediate subliminal or overtly perceived peripheral stimulation during TES. We argue that peripheral co-stimulation may contribute to the behavioral effects of TES and should be controlled for by “sham” TES. We discuss biophysical properties of TES, which need to be considered, if one wishes to make realistic assumptions about which brain regions were preferentially targeted by TES. Using results from electric field calculations, we evaluate the validity of different strategies that have been used for selective spatial targeting. Finally, we comment on the challenge of adjusting the dose of TES considering dose–response relationships between the weak tissue currents and the physiological effects in targeted cortical areas. These considerations call for caution when attributing behavioral effects during or after low-intensity TES studies to a specific brain region and may facilitate the selection of best practices for future TES studies.

Focal transcranial magnetic stimulation (TMS) of the rat brain: coil design, c-fos mapping and electrophysiology

Introduction: Rodent studies could be of great value in understanding the neurobiological mechanism of TMS. Unfortunately, there is no commercial rodent TMS coil that can mimic the spatial focality of human TMS. We report a novel system capable of inducing focal stimulation of the rat and mouse brains, with an estimate focality of about 1 mm.

Ipsilateral motor evoked potentials in a patient with unihemispheric cortical atrophy due to Rasmussen encephalitis.

The role of the ipsilaterally descending motor pathways in the recovery mechanisms after unilateral hemispheric damage is still poorly understood. Motor output reorganization was investigated in a 56-year-old male patient with acquired unilateral hemispheric atrophy due to Rasmussen encephalitis. In particular, the ipsilateral corticospinal pathways were explored using focal transcranial magnetic stimulation. In the first dorsal interosseous and wrist extensors muscles, the median amplitudes of the ipsilateral motor evoked potentials induced by transcranial magnetic stimulation in the patient were higher than those of 10 age-matched healthy control subjects. In the biceps brachii muscle, the median amplitudes of the ipsilateral motor evoked potentials were the second largest in the patient compared to the controls. This study demonstrated a reinforcement of ipsilateral motor projections from the unaffected motor cortex to the hemiparetic hand in a subject with acquired unihemispheric cortical damage.

Perturbation of left posterior prefrontal cortex modulates top-down processing in sentence comprehension

Communication is an inferential process. In particular, language comprehension constantly requires top-down efforts, as often multiple interpretations are compatible with a given sentence. To assess top-down processing in the language domain, our experiment employed ambiguous sentences that allow for multiple interpretations (e.g., The client sued the murderer with the corrupt lawyer., where the corrupt lawyer could either belong to The client or the murderer). Interpretation thus depended on whether participants chunk the words of the sentence into short or long syntactic phrases. In principle, bottom-up acoustic information (i.e., the presence or absence of an intonational phrase boundary at the offset of the murderer) indicates one of the two possible interpretations. Yet, acoustic information often indicates interpretations that require words to be chunked into overly long phrases that would overburden working memory. Processing is biased against these demands, reflected in a top-down preference to chunk words into short rather than long phrases. It is often proposed, but also hotly debated, that the ability to chunk words into short phrases is subserved by the left inferior frontal gyrus (IFG). Here, we employed focal repetitive transcranial magnetic stimulation to perturb the left IFG, which resulted in a further decrease of the aptitude to tolerate long phrases, indicating the inability of the left IFG to assist the chunking of words into phrases. In contrast, the processing of auditory information was not affected. Our findings support a causal top-down role of the left inferior frontal gyrus in the chunking of words into phrases.

F193. What remains as transcranial cortical response after accounting for the contribution of somatosensory and auditory evoked responses?

Focal transcranial magnetic stimulation (TMS) induces somatosensory input due to excitation of peripheral trigeminal nerve branches as well as auditory input caused by the loud click produced during stimulus discharge. In a recent study, we have demonstrated that these peripheral sources of cortical activation make a strong contribution to the transcranial evoked potentials (TEPs) that can be recorded with EEG at the scalp. Here we investigated the components of the TEP after removal of multisensory contributions. In 10 healthy young volunteers, we applied single-pulse neuronavigated TMS using two coil orientations (perpendicular and parallel to the target gyrus) and two positions (superior frontal gyrus and superior parietal lobule) and recorded the TEPs. We also recorded the evoked EEG response in a sham condition during which the TMS click was given simultaneously with bipolar electrical skin stimulation at the site corresponding to the centre of the coil during real TMS. We applied a fitting procedure to the sham and real-TMS conditions to exclude the signal related to somatosensory and auditory processing from the transcranially evoked TMS response. Some of the standard peaks commonly reported in the TMS/EEG literature were reduced or modified, suggesting that they were also caused by multisensory peripheral stimulation. For example, this was the case for the negative deflection that appears at around 100 ms after single-pulse TMS. We also identified TEP components which were not changed after accounting for somatosensory and auditory EEG response. This uncovered TEP signal was sensitive to the direction of the coil orientation, showing statistical difference in time intervals that were not present in the original TEP. This study confirms the need to exclude the somatosensory and auditory confounds in order to have a deeper insight into the TMS/EEG results. The appropriate approach is to include a sham procedure that controls for the contribution of peripheral sensory stimulation to the TEPs. Our novel procedure renders it possible to study the brain response to direct magnetic stimulation of the cortex also in time intervals affected or covered by unwanted sensory inputs.

Centre-surround organization of fast sensorimotor integration in human motor hand area

Using the short-latency afferent inhibition (SAI) paradigm, transcranial magnetic stimulation (TMS) of the primary motor hand area (M1HAND) can probe how sensory input from limbs modulates corticomotor output in humans. Here we applied a novel TMS mapping approach to chart the spatial representation of SAI in human hand-knob. We hypothesized SAI is somatotopically expressed in M1HAND depending on both the site of peripheral electrical nerve stimulation and the cortical spot targeted by TMS within M1HAND. The left index or little finger was stimulated 23 ms before focal single-pulse TMS of the right M1HAND. Using frameless stereotaxy, we applied biphasic-TMS pulses at seven stimulation positions above right M1HAND and recorded the motor evoked potentials (MEPs) from relaxed left first-dorsal-interosseous (FDI) and abductor-digiti-minimi (ADM) muscles. Homotopic stimulation of the finger close to the muscle targeted by TMS revealed a somatotopic expression of afferent inhibition matching the somatotopic representation of unconditioned MEPs (homotopic SAI). Conversely, heterotopic stimulation of a finger distant to the muscle targeted by TMS induced short-latency afferent facilitation (SAF) of MEPs in M1HAND. Like homotopic SAI, heterotopic SAF was somatotopically expressed in M1HAND. Together, the results provide first-time evidence that fast sensorimotor integration involves centre-inhibition and surround-facilitation in human M1HAND.

Modulation of corticospinal excitability by valerian officinalis root extract: A neuropharmacological Transcranial Magnetic Stimulation (TMS) study

IntroductionValerian officinalis roots extract is a popular medication for insomnia and anxiety treatment. Sedative effect of Valerian is mainly attributed to the modulation of gabaergic transmission, but its pharmacodynamics has not been fully elucidated.ObjectsTo investigate the acute effects of Valerian Officinalis extracts intake on corticoexcitability as measured by TMS.AimsTo obtain further data on Valerian pharmacodynamics.MethodsTwelve healthy volunteers participated in a double-blind randomized crossover placebo-controlled study. They were required to take either 900 mg of Valerian officinalis extract (valerenic acid 0.8%) or placebo. Focal TMS of the hand area of left motor cortex was used to test Resting motor threshold (RMT), Motor evoked potentials (MEPs) amplitude and silent period duration (SP). We also tested Short-interval Intracortical Inhibition (SICI), Intracortical facilitation (ICF), Short and Long afferent Inhibition (SAI and LAI). All parameters were investigated at baseline, 1 hour and 6 hours after drug intake. After a 3-week washout period the subjects switched to the alternate arm of the study.ResultsA mixed RMANOVA revealed a significant main effect of “time” [F(1,22) = 4.03, P = 0.02] and a significant “treatment × time” interaction [F(1,22) = 6.3, P = 0.003]. Post-hoc analysis indicated that the amount of ICF was significantly reduced 1 hour after Valerian intake (P = 0.01) returning to baseline values after 6 hours. No significant changes between the Valerian and placebo groups were observed for the other parameters investigated.ConclusionsThe modulation of ICF induced by Valerian officinalis is likely due to glutamatergic antagonism and might underlie the anti-anxiety therapeutic effects.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Characteristics of corticospinal projections to the intrinsic hand muscles in skilled harpists

The process of learning to play a musical instrument necessarily alters the functional organisation of the cortical motor areas that are involved in generating the required movements. In the case of the harp, the demands placed on the motor system are quite specific. During performance, all digits with the sole exception of the little finger are used to pluck the strings. With a view to elucidating the impact of having acquired this highly specialised musical skill on the characteristics of corticospinal projections to the intrinsic hand muscles, focal transcranial magnetic stimulation (TMS) was used to elicit motor evoked potentials (MEPs) in three muscles (of the left hand): abductor pollicis brevis (APB); first dorsal interosseous (FDI); and abductor digiti minimi (ADM) in seven harpists. Seven non-musicians served as controls. With respect to the FDI muscle—which moves the index finger, the harpists exhibited reliably larger MEP amplitudes than those in the control group. In contrast, MEPs evoked in the ADM muscle—which activates the little finger, were smaller in the harpists than in the non-musicians. The locations on the scalp over which magnetic stimulation elicited discriminable responses in ADM also differed between the harpists and the non-musicians. This specific pattern of variation in the excitability of corticospinal projections to these intrinsic hand muscles exhibited by harpists is in accordance with the idiosyncratic functional demands that are imposed in playing this instrument.