A transcranial magnetic stimulation protocol for decreasing the craving of methamphetamine-dependent patients.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Many substance use disorders lack effective treatments, and TMS is expected to reduce cravings and risk of relapse by regulating brain function. Here, we introduce three alternative TMS settings and specific operations to interfere with methamphetamine use disorders. Theoretically, this protocol can also be applied to diseases with similar brain damage characteristics. For complete details on the use and execution of this protocol, please refer to Chen et al. (2020).

In vivo local transcranial static magnetic field stimulation alters motor behavior in normal rats.

Transcranial static magnetic field stimulation (tSMS) has inhibitory neuromodulatory effects on the human brain. Most of the studies on static magnetic fields have been performed in vitro. To further understand the biological mechanisms of tSMS, we investigated the effects of in vivo tSMS on motor behavior in normal awake rats. The skull of a male Wistar rat was exposed and a polyethylene tube was attached to the skull using dental cement at the center of the motor cortex (n = 7) or the other cortex (n = 6). By attaching a cylindrical NdFeB neodymium magnet into the tube, in vivo tSMS (REAL) was performed. For SHAM, we applied a similar size non-magnetic stainless-steel cylinder. All rats received twice each SHAM and REAL stimulation every two days using a crossover design, and motor function was measured during the stimulation. Activity level and asymmetry of forelimb use were not affected, but less accurate movements in the horizontal ladder test were found in REAL stimulation of the motor cortex. This study shows that in vivo tSMS has inhibitory neuromodulatory effects on motor behavior depending on the stimulated region on the rat cortex.

Specific modulation of corticomuscular coherence during submaximal voluntary isometric, shortening and lengthening contractions.

During voluntary contractions, corticomuscular coherence (CMC) is thought to reflect a mutual interaction between cortical and muscle oscillatory activities, respectively measured by electroencephalography (EEG) and electromyography (EMG). However, it remains unclear whether CMC modulation would depend on the contribution of neural mechanisms acting at the spinal level. To this purpose, modulations of CMC were compared during submaximal isometric, shortening and lengthening contractions of the soleus (SOL) and the medial gastrocnemius (MG) with a concurrent analysis of changes in spinal excitability that may be reduced during lengthening contractions. Submaximal contractions intensity was set at 50% of the maximal SOL EMG activity. CMC was computed in the time-frequency domain between the Cz EEG electrode signal and the unrectified SOL or MG EMG signal. Spinal excitability was quantified through normalized Hoffmann (H) reflex amplitude. The results indicate that beta-band CMC and normalized H-reflex were significantly lower in SOL during lengthening compared with isometric contractions, but were similar in MG for all three muscle contraction types. Collectively, these results highlight an effect of contraction type on beta-band CMC, although it may differ between agonist synergist muscles. These novel findings also provide new evidence that beta-band CMC modulation may involve spinal regulatory mechanisms.

Cerebellar rTMS and PAS effectively induce cerebellar plasticity.

Non-invasive brain stimulation techniques including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), paired associative stimulation (PAS), and transcranial direct current stimulation (tDCS) have been applied over the cerebellum to induce plasticity and gain insights into the interaction of the cerebellum with neo-cortical structures including the motor cortex. We compared the effects of 1 Hz rTMS, cTBS, PAS and tDCS given over the cerebellum on motor cortical excitability and interactions between the cerebellum and dorsal premotor cortex / primary motor cortex in two within subject designs in healthy controls. In experiment 1, rTMS, cTBS, PAS, and tDCS were applied over the cerebellum in 20 healthy subjects. In experiment 2, rTMS and PAS were compared to sham conditions in another group of 20 healthy subjects. In experiment 1, PAS reduced cortical excitability determined by motor evoked potentials (MEP) amplitudes, whereas rTMS increased motor thresholds and facilitated dorsal premotor-motor and cerebellum-motor cortex interactions. TDCS and cTBS had no significant effects. In experiment 2, MEP amplitudes increased after rTMS and motor thresholds following PAS. Analysis of all participants who received rTMS and PAS showed that MEP amplitudes were reduced after PAS and increased following rTMS. rTMS also caused facilitation of dorsal premotor-motor cortex and cerebellum-motor cortex interactions. In summary, cerebellar 1 Hz rTMS and PAS can effectively induce plasticity in cerebello-(premotor)-motor pathways provided larger samples are studied.

Ten minutes of transcranial static magnetic field stimulation does not reliably modulate motor cortex excitability.

Recently, modulatory effects of static magnetic field stimulation (tSMS) on excitability of the motor cortex have been reported. In our previous study we failed to replicate these results. It was suggested that the lack of modulatory effects was due to the use of an auditory oddball task in our study. Thus, we aimed to evaluate the role of an oddball task on the effects of tSMS on motor cortex excitability. In a within-subject-design we compared 10 minutes tSMS with and without oddball task. In one of the two sessions subjects had to solve an auditory oddball task during the exposure to the magnet, whereas there was no task during exposure in the other session. Motor cortex excitability was measured before and after tSMS. No modulation was observed in any condition. However, when data were pooled regarding the order of the sessions, a trend for an increase of excitability was observed in the first session compared to the second session. We now can rule out that the auditory oddball task destroys tSMS effects, as postulated. Our results rather suggest that fluctuations in the amplitudes of single pulse motor evoked potentials may possibly mask weak modulatory effects but may also lead to false positive results if the number of subjects in a study is too low. In addition, there might be a habituation effect to the whole procedure, resulting in less variability when subjects underwent the same experiment twice.

Resting-state fMRI study of brain activation using low-intensity repetitive transcranial magnetic stimulation in rats.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used to treat many neuropsychiatric conditions. However, the mechanisms underlying its mode of action are still unclear. This is the first rodent study using resting-state functional MRI (rs-fMRI) to examine low-intensity (LI) rTMS effects, in an effort to provide a direct means of comparison between rodent and human studies. Using anaesthetised Sprague-Dawley rats, rs-fMRI data were acquired before and after control or LI-rTMS at 1 Hz, 10 Hz, continuous theta burst stimulation (cTBS) or biomimetic high-frequency stimulation (BHFS). Independent component analysis revealed LI-rTMS-induced changes in the resting-state networks (RSN): (i) in the somatosensory cortex, the synchrony of resting activity decreased ipsilaterally following 10 Hz and bilaterally following 1 Hz stimulation and BHFS, and increased ipsilaterally following cTBS; (ii) the motor cortex showed bilateral changes following 1 Hz and 10 Hz stimulation, a contralateral decrease in synchrony following BHFS, and an ipsilateral increase following cTBS; and (iii) hippocampal synchrony decreased ipsilaterally following 10 Hz, and bilaterally following 1 Hz stimulation and BHFS. The present findings demonstrate that LI-rTMS modulates functional links within the rat RSN with frequency-specific outcomes, and the observed changes are similar to those described in humans following rTMS.

Effects of repetitive transcranial magnetic stimulation on masseter motor-neuron pool excitability.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been widely used to modulate the excitability of the cortical control of limbs muscles, but rarely in the cortical control of human masseter muscles. This study aims to investigate the effects of rTMS on masseter motor-neuron pool excitability in humans. MATERIALS AND METHODS: A total of 20 healthy participants were selected and received a total of three rTMS sessions involving stimulation of the right masseter-motor complex: one session of 10-Hz rTMS, one session of 1-Hz rTMS and one session of sham rTMS at an intensity of 80% of the active motor threshold (AMT). The masseter AMT, motor-evoked potentials (MEPs), cortical-silent period (CSP), and short-interval intracortical inhibition (SICI) were measured before and after each rTMS session. RESULTS: The masseter SICI was significantly decreased following 10-Hz rTMS, with no significant changes in AMT, MEPs or CSP. No significant differences in masseter AMT, MEPs, CSP or SICI were observed in either the 1-Hz, or sham rTMS groups. CONCLUSIONS: The present findings demonstrate that high-frequency rTMS increases masseter motor-neuron pool excitability.

Motor evoked potentials in standing and recumbent calves induced by magnetic stimulation at the foramen magnum.

The aims of this study were to determine reference values for magnetic motor evoked potentials (mMEPs) in calves and the influence of position during examination (standing or lateral recumbency). Reference values were determined using 41 healthy Holstein Friesian bull calves aged 1-10 months; standing and lateral recumbency were examined in 11 calves. Maximal magnetic stimulation was performed at the level of the foramen magnum with a magnetic field of 4 T at the coil surface. In standing position, distinct, reproducible mMEPs were obtained in all calves. Onset latency (LAT) (mean ± standard deviation) was significantly shorter in the thoracic limbs (34.4 ± 3.1 ms) than in the pelvic limbs (44.6 ± 3.0 ms). Amplitude (AMPL) was significantly higher in the thoracic limbs (3.7 ± 1.7 mV) than in the pelvic limbs (3.3 ± 1.7 mV) and significantly increased with body length. Age, body weight, height at the withers and rectal temperature had no significant association with LAT or AMPL, and no differences between left and right were noted. In the lateral position, only 64% of the calves showed responses in the four limbs; in these calves, LAT (29.7 ± 4.7 ms) and AMPL (3.0 ± 1.8 mV) in the thoracic limbs were significantly different from AMPL (47.0 ± 7.4 ms) and LAT (2.1 ± 2.1 mV) in the pelvic limbs. In conclusion, mMEPs in limb muscles can be evoked in calves by stimulation at the level of the foramen magnum. mMEPs are more difficult to obtain in lateral recumbency than in standing calves.

Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation.

OBJECTIVE: Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response. Particularly, we sought to discover the E-field characteristics that lead to cortical activation. APPROACH: Subject-specific finite element models (FEMs) of the head and brain were constructed for each of six subjects using magnetic resonance image scans. Positron emission tomography (PET) measured each subject's cortical response to image-guided robotically-positioned TMS to the primary motor cortex. FEM models that employed the given coil position, orientation, and stimulus intensity in experimental applications of TMS were used to calculate the electric field (E-field) vectors within a region of interest for each subject. TMS-induced E-fields were analyzed to better understand what vector components led to regional cerebral blood flow (CBF) responses recorded by PET. MAIN RESULTS: This study found that decomposing the E-field into orthogonal vector components based on the cortical surface geometry (and hence, cortical neuron directions) led to significant differences between the regions of cortex that were active and nonactive. Specifically, active regions had significantly higher E-field components in the normal inward direction (i.e., parallel to pyramidal neurons in the dendrite-to-axon orientation) and in the tangential direction (i.e., parallel to interneurons) at high gradient. In contrast, nonactive regions had higher E-field vectors in the outward normal direction suggesting inhibitory responses. SIGNIFICANCE: These results provide critical new understanding of the factors by which TMS induces cortical activation necessary for predictive and repeatable use of this noninvasive stimulation modality.

New treatment alternatives in the ulnar neuropathy at the elbow: ultrasound and low-level laser therapy.

Ulnar nerve entrapment at the elbow (UNE) is the second most common entrapment neuropathy of the arm. Conservative treatment is the treatment of choice in mild to moderate cases. Elbow splints and avoiding flexion of the involved elbow constitute majority of the conservative treatment; indeed, there is no other non-invasive treatment modality. The aim of this study was to investigate the efficacy of ultrasound (US) and low-level laser therapy (LLLT) in the treatment of UNE to provide an alternative conservative treatment method. A randomized single-blind study was carried out in 32 patients diagnosed with UNE. Short-segment conduction study (SSCS) was performed for the localization of the entrapment site. Patients were randomized into US treatment (frequency of 1 MHz, intensity of 1.5 W/cm(2), continuous mode) and LLLT (0.8 J/cm(2) with 905 nm wavelength), both applied five times a week for 2 weeks. Assessments were performed at baseline, at the end of the treatment, and at the first and third months by visual analog scale, hand grip strength, semmes weinstein monofilament test, latency change at SSCS, and patient satisfaction scale. Both treatment groups had significant improvements on clinical and electrophysiological parameters (p < 0.05) at first month with no statistically significant difference between them. Improvements in all parameters were sustained at the third month for the US group, while only changes in grip strength and latency were significant for the LLLT group at third month. The present study demonstrated that both US and LLLT provided improvements in clinical and electrophysiological parameters and have a satisfying short-term effectiveness in the treatment of UNE.

Transcranial application of near-infrared low-level laser can modulate cortical excitability.

BACKGROUND AND OBJECTIVE: Near-infrared low-level laser (NIR-LLL) irradiation penetrates scalp and skull and can reach superficial layers of the cerebral cortex. It was shown to improve the outcome of acute stroke in both animal and human studies. In this study we evaluated whether transcranial laser stimulation (TLS) with NIR-LLL can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS). METHODS: TLS was applied for 5 minutes over the representation of the right first dorsal interosseal muscle (FDI) in left primary motor cortex (M1), in 14 healthy subjects. Motor evoked potentials (MEPs) from the FDI, elicited by single-pulse TMS, were measured at baseline and up to 30 minutes after the TLS. RESULTS: The average MEP size was significantly reduced during the first 20 minutes following the TLS. The pattern was present in 10 (71.5%) of the participants. The MEP size reduction correlated negatively with the motor threshold at rest. CONCLUSIONS: TLS with NIR-LLL induced transitory reduction of the excitability of the stimulated cortex. These findings give further insights into the mechanisms of TLS effects in the human cerebral cortex, paving the way for potential applications of TLS in treatment of stroke and in other clinical settings.

The role of left supplementary motor area in grip force scaling.

Skilled tool use and object manipulation critically relies on the ability to scale anticipatorily the grip force (GF) in relation to object dynamics. This predictive behaviour entails that the nervous system is able to store, and then select, the appropriate internal representation of common object dynamics, allowing GF to be applied in parallel with the arm motor commands. Although psychophysical studies have provided strong evidence supporting the existence of internal representations of object dynamics, known as "internal models", their neural correlates are still debated. Because functional neuroimaging studies have repeatedly designated the supplementary motor area (SMA) as a possible candidate involved in internal model implementation, we used repetitive transcranial magnetic stimulation (rTMS) to interfere with the normal functioning of left or right SMA in healthy participants performing a grip-lift task with either hand. TMS applied over the left, but not right, SMA yielded an increase in both GF and GF rate, irrespective of the hand used to perform the task, and only when TMS was delivered 130-180 ms before the fingers contacted the object. We also found that both left and right SMA rTMS led to a decrease in preload phase durations for contralateral hand movements. The present study suggests that left SMA is a crucial node in the network processing the internal representation of object dynamics although further experiments are required to rule out that TMS does not affect the GF gain. The present finding also further substantiates the left hemisphere dominance in scaling GF.

Effects of simultaneous bilateral tDCS of the human motor cortex.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive technique that has been investigated as a therapeutic tool for different neurologic disorders. Neuronal excitability can be modified by application of DC in a polarity-specific manner: anodal tDCS increases excitability, while cathodal tDCS decreases excitability. Previous research has shown that simultaneous bilateral tDCS of the human motor cortex facilitates motor performance in the anodal stimulated hemisphere much more than when the same hemisphere is stimulated using unilateral anodal motor cortex tDCS. OBJECTIVE: The main purpose of this study was to determine whether simultaneous bilateral tDCS is able to increase cortical excitability in one hemisphere whereas decreasing cortical excitability in the contralateral hemisphere. To test our hypothesis, cortical excitability before and after bilateral motor cortex tDCS was evaluated. Moreover, the effects of bilateral tDCS were compared with those of unilateral motor cortex tDCS. METHODS: We evaluated cortical excitability in healthy volunteers before and after unilateral or bilateral tDCS using transcranial magnetic stimulation. RESULTS: We demonstrated that simultaneous application of anodal tDCS over the motor cortex and cathodal tDCS over the contralateral motor cortex induces an increase in cortical excitability on the anodal-stimulated side and a decrease in the cathodal stimulated side. We also used the electrode montage (motor cortex-contralateral orbit) method to compare the bilateral tDCS montage with unilateral tDCS montage. The simultaneous bilateral tDCS induced similar effects to the unilateral montage on the cathode-stimulated side. On the anodal tDCS side, the simultaneous bilateral tDCS seems to be a slightly less robust electrode arrangement compared with the placement of electrodes in the motor cortex-contralateral orbit montage. We also found that intersubject variability of the excitability changes that were induced by the anodal motor cortex tDCS using the bilateral montage was lower than that with the unilateral montage. CONCLUSIONS: This is the first study in which cortical excitability before and after bilateral motor cortex tDCS was extensively evaluated, and the effects of bilateral tDCS were compared with unilateral motor cortex tDCS. Simultaneous bilateral tDCS seems to be a useful tool to obtain increases in cortical excitability of one hemisphere whereas causing decreases of cortical excitability in the contralateral hemisphere (e.g.,to treat stroke).

Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation.

BACKGROUND: Evidence from recent clinical trials suggests that transcranial direct current stimulation (tDCS) may have potential in treating neuropsychiatric disorders. However, the optimal frequency at which tDCS sessions should be administered is unknown. OBJECTIVE/HYPOTHESIS: This study investigated the effects of daily or second daily tDCS sessions on motor cortical excitability, over a 5-day period. METHODS: Twelve healthy volunteers received daily or second daily sessions of tDCS to the left primary motor cortex over the study period, in a randomized, intraindividual crossover design. Motor cortical excitability was assessed before and after tDCS at each session through responses to transcranial magnetic stimulation. RESULTS: Over a fixed 5-day period, tDCS induced greater increases in MEP amplitude when given daily rather than second daily. Analyses showed that this difference reflected greater cumulative effects between sessions rather than a greater response to each individual tDCS session. CONCLUSIONS: These results demonstrate that in the motor cortex of healthy volunteers, tDCS alters cortical excitability more effectively when given daily rather than second daily over a 5-day period.

Evaluating aftereffects of short-duration transcranial random noise stimulation on cortical excitability.

A 10-minute application of highfrequency (100-640 Hz) transcranial random noise stimulation (tRNS) over the primary motor cortex (M1) increases baseline levels of cortical excitability, lasting around 1 hr poststimulation Terney et al. (2008). We have extended previous work demonstrating this effect by decreasing the stimulation duration to 4, 5, and 6 minutes to assess whether a shorter duration of tRNS can also induce a change in cortical excitability. Single-pulse monophasic transcranial magnetic stimulation (TMS) was used to measure baseline levels of cortical excitability before and after tRNS. A 5- and 6-minute tRNS application induced a significant facilitation. 4-minute tRNS produced no significant aftereffects on corticospinal excitability. Plastic after effects after tRNS on corticospinal excitability require a minimal stimulation duration of 5 minutes. However, the duration of the aftereffect of 5-min tRNS is very short compared to previous studies using tRNS. Developing different transcranial stimulation techniques may be fundamental in understanding how excitatory and inhibitory networks in the human brain can be modulated and how each technique can be optimised for a controlled and effective application.

Inhibitory effects of visible 650-nm and infrared 808-nm laser irradiation on somatosensory and compound muscle action potentials in rat sciatic nerve: implications for laser-induced analgesia.

Low-level laser therapy (LLLT) has been shown in clinical trials to relieve chronic pain and the World Health Organization has added LLLT to their guidelines for treatment of chronic neck pain. The mechanisms for the pain-relieving effects of LLLT are however poorly understood. We therefore assessed the effects of laser irradiation (LI) on somatosensory-evoked potentials (SSEPs) and compound muscle action potentials (CMAPs) in a series of experiments using visible (λ = 650 nm) or infrared (λ = 808 nm) LI applied transcutaneously to points on the hind limbs of rats overlying the course of the sciatic nerve. This approximates the clinical application of LLLT. The 650-nm LI decreased SSEP amplitudes and increased latency after 20 min. CMAP proximal amplitudes and hip/ankle (H/A) ratios decreased at 10 and 20 min with increases in proximal latencies approaching significance. The 808-nm LI decreased SSEP amplitudes and increased latencies at 10 and 20 min. CMAP proximal amplitudes and H/A ratios decreased at 10 and 20 min. Latencies were not significantly increased. All LI changes for both wavelengths returned to baseline by 48 h. These results strengthen the hypothesis that a neural mechanism underlies the clinical effectiveness of LLLT for painful conditions.

Transcranial alternating current stimulation in the low kHz range increases motor cortex excitability.

PURPOSE: External transcranial electric and magnetic stimulation techniques allow for the fast induction of sustained and measurable changes in cortical excitability. Here we aim to develop a paradigm using transcranial alternating current (tACS) in a frequency range higher than 1 kHz, which potentially interferes with membrane excitation, to shape neuroplastic processes in the human primary motor cortex (M1). METHODS: Transcranial alternating current stimulation was applied at 1, 2 and 5 kHz over the left primary motor cortex with a reference electrode over the contralateral orbit in 11 healthy volunteers for a duration of 10 min at an intensity of 1 mA. Monophasic single- pulse transcranial magnetic stimulation (TMS) was used to measure changes in corticospinal excitability, both during and after tACS in the low kHz range, in the right hand muscle. As a control inactive sham stimulation was performed. RESULTS: All frequencies of tACS increased the amplitudes of motor- evoked potentials (MEPs) up to 30-60 min post stimulation, compared to the baseline. Two and 5 kHz stimulations were more efficacious in inducing sustained changes in cortical excitability than 1 kHz stimulation, compared to sham stimulation. CONCLUSIONS: Since tACS in the low kHz range appears too fast to interfere with network oscillations, this technique opens a new possibility to directly interfere with cortical excitability, probably via neuronal membrane activation. It may also potentially replace more conventional repetitive transcranial magnetic stimulation (rTMS) techniques for some applications in a clinical setting.

A simple head-mountable LED device for chronic stimulation of optogenetic molecules in freely moving mice.

We describe a low-cost, small, remotely triggerable LED device for wireless control of transcranial optical stimulation of cortical neurons, for use in freely moving mice. The device is easily mountable on the head of a mouse with a high-polymer block. Using the Thy1-ChR2-YFP transgenic mice, we demonstrate that the device is capable of remotely triggering muscle twitches upon activation of the primary motor cortex in freely moving conditions.

[Rules of application and mode of action of transcranial direct current stimulation in neurorehabilitation: primary motor cortex]. / Zasady stosowania i mechanizm dzialania przezczaszkowej stymulacji pradem stalym w neurorehabilitacji: dane z badan kory ruchowej.

Transcranial direct current stimulation (tDCS) is an emerging technique of non-invasive brain stimulation that has been found useful in facilitating treatment of various neurological disorders, especially stroke. Currently available criteria for single application of several minutes-long stimulation at 1-2 mA have been considered safe. However, knowledge regarding safety parameters of repeated and long-term electrical stimulation is so far limited. Studies on the use of tDCS focus predominantly on the motor cortex. They demonstrate that weak direct current is capable of eliciting cortical excitability changes which occur during and after stimulation. The nature of these changes is specific for current polarity - anodal stimulation enhances excitability, and cathodal reduces it. Studies indicate that tDCS effects are generated by polarity-driven alterations of membrane potentials and efficacy modulations of specific neuronal receptors. According to interhemispheric competition models, possible mechanisms underlying functional improvements due to stimulation in patients with stroke are attributed to tDCS-induced modification of inappropriate interhemispheric inhibition.

Reduced motor cortex plasticity following inhibitory rTMS in older adults.

OBJECTIVE: Ageing is accompanied by diminished practice-dependent plasticity. We investigated the effect of age on another plasticity inducing paradigm, repetitive transcranial magnetic stimulation (rTMS). METHODS: Healthy young (n=15; 25+/-4 years) and old (n=15; 67+/-5 years) adults participated in two experiments. Motor evoked potentials (MEPs) were measured in the target muscle (first dorsal interosseus, FDI) and a remote muscle (abductor digiti minimi) during a set of single stimuli. Subjects then received real or sham inhibitory rTMS (intermittent subthreshold trains of 6Hz stimulation for 10min). MEPs were measured for 30min after rTMS. RESULTS: In young adults, MEPs in the target FDI muscle were approximately 15% smaller in the real rTMS experiment than in the sham rTMS experiment (P<0.026). In old adults, FDI MEP size did not differ between experiments. CONCLUSIONS: Advancing age is associated with reduced efficacy of inhibitory rTMS. SIGNIFICANCE: This work has important implications for the potential therapeutic use of rTMS in stroke and neurological disease.