Transcranial Magnetic Stimulation Protocol Research Articles

Modulating intrinsic functional connectivity with visual cortex using low-frequency repetitive transcranial magnetic stimulation.

IntroductionIntrinsic network connectivity becomes altered in pathophysiology. Noninvasive brain stimulation can modulate pathological functional networks in an attempt to restore the inherent response. To determine its usefulness for visual‐related disorders, we developed procedures investigating repetitive transcranial magnetic stimulation (rTMS) protocols targeting the visual cortex on modulating connectivity associated with the visual network and default mode network (DMN).MethodsWe compared two low‐frequency (1 Hz) rTMS protocols to the visual cortex (V1)—a single 20 min session and five successive 20 min sessions (accelerated/within‐session rTMS)—using multi‐echo resting‐state functional magnetic resonance whole‐brain imaging and resting‐state functional connectivity (rsFC). We also explored the relationship between rsFC and rTMS‐induced changes in key inhibitory and excitatory neurotransmitters, γ‐aminobutyric acid (GABA) and glutamate. GABA (GABA+) and glutamate (Glx) concentrations were measured in vivo using magnetic resonance spectroscopy.ResultsAcute disruption with a single rTMS session caused widespread connectivity reconfiguration with nodes of interest. Changes were not evident immediately post‐rTMS but were observed at 1 h post‐rTMS. Accelerated sessions resulted in weak alterations in connectivity, producing a relatively homeostatic response. Changes in GABA+ and Glx concentrations with network connectivity were dependent on the rTMS protocol.ConclusionsThis proof‐of‐concept study offers new perspectives to assess stimulation‐induced neural processes involved in intrinsic functional connectivity and the potential for rTMS to modulate nodes interconnected with the visual cortex. The differential effects of single‐session and accelerated rTMS on physiological markers are crucial for furthering the advancement of treatment modalities in visual cortex related disorders.

Chapter 5 - Transcranial magnetic stimulation as a tool to induce and explore plasticity in humans

Activity-dependent synaptic plasticity is the main theoretical framework to explain mechanisms of learning and memory. Synaptic plasticity can be explored experimentally in animals through various standardized protocols for eliciting long-term potentiation and long-term depression in hippocampal and cortical slices. In humans, several non-invasive protocols of repetitive transcranial magnetic stimulation and transcranial direct current stimulation have been designed and applied to probe synaptic plasticity in the primary motor cortex, as reflected by long-term changes in motor evoked potential amplitudes. These protocols mimic those normally used in animal studies for assessing long-term potentiation and long-term depression. In this chapter, we first discuss the physiologic basis of theta-burst stimulation, paired associative stimulation, and transcranial direct current stimulation. We describe the current biophysical and theoretical models underlying the molecular mechanisms of synaptic plasticity and metaplasticity, defined as activity-dependent changes in neural functions that modulate subsequent synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD), in the human motor cortex including calcium-dependent plasticity, spike-timing-dependent plasticity, the role of N-methyl-d-aspartate-related transmission and gamma-aminobutyric-acid interneuronal activity. We also review the putative microcircuits responsible for synaptic plasticity in the human motor cortex. We critically readdress the issue of variability in studies investigating synaptic plasticity and propose available solutions. Finally, we speculate about the utility of future studies with more advanced experimental approaches.

Chapter 21 - New tools for shaping plasticity to enhance recovery after stroke

Stroke is the second most common cause of death worldwide and its prevalence is projected to increase in the coming years in parallel with the increase of life expectancy. Despite the great improvements in the management of the acute phase of stroke, some residual disability persists in most patients thus requiring rehabilitation. One third of patients do not reach the maximal recovery potential and different approaches have been explored with the aim to boost up recovery. In this regard, noninvasive brain stimulation techniques have been widely used to induce neuroplasticity phenomena. Different protocols of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) can induce short- and long-term changes of synaptic excitability and are promising tools for enhancing recovery in stroke patients. New options for neuromodulation are currently under investigation. They include: vagal nerve stimulation (VNS) that can be delivered invasively, with implanted stimulators and noninvasively with transcutaneous VNS (tVNS); and extremely low-frequency (1-300Hz) magnetic fields. This chapter will provide an overview on the new techniques that are used for neuroprotection and for enhancing recovery after stroke.

Effects of non-invasive brain stimulation in multiple sclerosis: systematic review and meta-analysis.

Objective:The objective of this meta-analysis was to summarize evidence on the therapeutic effects of non-invasive brain stimulation (NIBS) on core symptoms of multiple sclerosis (MS). Specifically, findings from studies deploying transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) protocols were summarized in this review.Methods:We systematically searched articles published in four databases, until 31 May 2021, which compared the effects of active tDCS or rTMS with sham intervention in MS patients. We used a random-effects model for this meta-analysis. Meta-regression and subgroup meta-analysis were used to examine the effects of stimulation dose and different stimulation protocols, respectively.Results:Twenty-five randomized controlled trials (RCTs) were included in this review, consisting of 19 tDCS and 6 rTMS studies. tDCS led to a significant and immediate reduction of fatigue with a large effect size (Hedges’s g = −0.870, 95% confidence intervals (CI) = [−1.225 to −0.458], number needed to treat (NNT) = 2). Particularly, a subgroup analysis showed that applying tDCS over the left DLPFC and bilateral S1 led to fatigue reductions compared to sham stimulation. Furthermore, tDCS had favorable effects on fatigue in MS patients with low physical disability but not those with high physical disability, and additionally improved cognitive function. Finally, whereas rTMS was observed to reduce muscle spasticity, these NIBS protocols showed no further effect on MS-associated pain and mood symptoms.Conclusion:tDCS in MS alleviates fatigue and improves cognitive function whereas rTMS reduces muscle spasticity. More high-quality studies are needed to substantiate the therapeutic effects of different NIBS protocols in MS.

Tailored repetitive transcranial magnetic stimulation for depression and addictions.

Transcranial magnetic stimulation (TMS) has been widely applied for evaluation of the cortical eloquence through creation of the temporary "virtual lesion" allowing assessment of the evaluated function within the targeted region, which may be also employed for management of mental symptoms or modification of the abnormal behavior. It is believed that this non-invasive neuromodulation modality has a double impact on neurons-primary modulation of electrical activity and stimulation of neuroplasticity; the latter can be facilitated by repeated administration of TMS during multiple sessions over sufficiently long periods of time to induce consolidation of treatment effects through their recall at psychological, physiological, and cellular levels. These principles were employed in our data-driven, tailored strategy based on the modifications of TMS protocol and its adaptation to newly appearing changes of the clinical situation along with administration of prolonged and/or repeated courses of therapeutic stimulation, which showed high efficacy resulting in complete relief of depressive symptoms or substance use in 75% of treated patients at 1-year follow-up. Such results justify application of repetitive TMS for management of psychiatric disorders and warrant additional evaluation of its efficacy in further clinical studies.

Impact of operator experience on transcranial magnetic stimulation

ObjectiveTo determine the impact of an operator’s experience on transcranial magnetic stimulation (TMS) measurement. MethodsOperator B (beginner), operator E (expert), and 30 healthy participants joined the study consisting of two experiments. In each experiment, each operator performed a TMS protocol on each participant in a random order. ResultsCompared with operator E, operator B exhibited higher resting motor threshold (RMT) in experiment I (60.1 ± 13.0 vs. 57.4 ± 10.9% maximal stimulation output, p = 0.017) and the difference disappeared in experiment II (p = 0.816). In 1-mV motor evoked potential (MEP) measurement, operator B exhibited higher standard deviation indicating lower consistency in experiment I compared with experiment II (1.05 ± 0.40 vs. 1.05 ± 0.16 mV with unequal variances, p = 0.001) and had poor intrarater reliability between the experiments (intraclass correlation coefficient = −0.130). There was no difference in the results of active motor threshold, silent period, paired-pulse stimulation, or continuous theta burst stimulation between the operators. ConclusionsAn operator’s experience in TMS may affect the results of RMT measurement. With practice, a beginner may choose a more precise stimulation location and have higher consistency in 1-mV MEP measurement. SignificanceWe recommend that a beginner needs to practice for precise stimulation locations before conducting a trial or clinical practice.

Transcranial magnetic stimulation in the treatment of depressive disorder in Parkinson's disease

The prevalence of affective disorders in patients with Parkinson's disease (PD) is significantly higher than in the general population of people of the same age. It is known that the effectiveness of antidepressants in PD with depressive disorder is lower than in patients with primary depression. For depression resistant to standard treatments, other therapeutic strategies are available. Transcranial magnetic stimulation (TMS) is one of the most popular and safe brain stimulation methods that has been successfully used to treat primary depression. The accumulation of experience in the use of TMS has made it possible to expand the application of the method to other diseases, including PD. The article provides literature data on the use of different TMS protocols for the treatment of depressive disorder in patients with PD.

A Preclinical Study of Standard Versus Accelerated Transcranial Magnetic Stimulation for Depression in Adolescents.

Objective: Ongoing studies are focused on adapting transcranial magnetic stimulation (TMS) for the treatment of major depressive disorder in adolescent humans. Most protocols in adolescent humans to date have delivered daily 10 Hz prefrontal stimulation with mixed results. Novel TMS dosing strategies such as accelerated TMS have recently been considered. There are knowledge gaps related to the potential clinical and pragmatic advantages of accelerated TMS. This pilot study compared the behavioral effects of a standard daily and accelerated low-intensity TMS (LI-TMS) protocol in an adolescent murine model of depression. Methods: Male adolescent Sprague Dawley rats were placed in transparent plexiglass tubes for 2.5 hours daily for 13 days as part of a study to validate the chronic restraint stress (CRS) protocol. Rats subsequently received 10 minutes of active or sham 10 Hz LI-TMS daily for 2 weeks (standard) or three times daily for 1 week (accelerated). Behavior was assessed using the elevated plus maze and forced swim test (FST). Hippocampal neurogenesis was assessed by injection of the thymidine analogue 5-ethynyl-2'-deoxyuridine at the end of LI-TMS treatment (2 weeks standard, 1 week accelerated), followed by postmortem histological analysis. Results: There were no significant differences in behavioral outcomes among animals receiving once-daily sham or active LI-TMS treatment. However, animals treated with accelerated LI-TMS demonstrated significant improvements in behavioral outcomes compared with sham treatment. Specifically, animals receiving active accelerated treatment showed greater latency to the first immobility behavior (p < 0.05; active: 130 ± 46 seconds; sham: 54 ± 39 seconds) and increased climbing behaviors (p < 0.05; active: 16 ± 5; sham: 9 ± 5) during FST. There were no changes in hippocampal neurogenesis nor any evidence of cell death in histological sections. Conclusions: An accelerated LI-TMS protocol outperformed the standard (once-daily) protocol in adolescent male animals with depression-like behaviors induced by CRS and was not accompanied by any toxicity or tolerability concerns. These preliminary findings support the speculation that novel TMS dosing strategies should be studied in adolescent humans and will inform future clinical protocols.

Face-hand sensorimotor interactions revealed by afferent inhibition.

Reorganization of the sensorimotor cortex following permanent (e.g., amputation) or temporary (e.g., local anaesthesia) deafferentation of the hand has revealed large-scale plastic changes between the hand and face representations that are accompanied by perceptual correlates. The physiological mechanisms underlying this reorganization remain poorly understood. The aim of this study was to investigate sensorimotor interactions between the face and hand using an afferent inhibition transcranial magnetic stimulation protocol in which the motor evoked potential elicited by the magnetic pulse is inhibited when it is preceded by an afferent stimulus. We hypothesized that if face and hand representations in the sensorimotor cortex are functionally coupled, then electrocutaneous stimulation of the face would inhibit hand muscle motor responses. In two separate experiments, we delivered an electrocutaneous stimulus to either the skin over the right upper lip (Experiment 1) or right cheek (Experiment 2) and recorded muscular activity from the right first dorsal interosseous. Both lip and cheek stimulation inhibited right first dorsal interosseous motor evoked potentials. To investigate the specificity of this effect, we conducted two additional experiments in which electrocutaneous stimulation was applied to either the right forearm (Experiment 3) or right upper arm (Experiment 4). Forearm and upper arm stimulation also significantly inhibited the right first dorsal interosseous motor evoked potentials, but this inhibition was less robust than the inhibition associated with face stimulation. These findings provide the first evidence for face-to-hand afferent inhibition.

Short-interval intracortical inhibition and facilitation targeting upper and lower limb muscles

Transcranial magnetic stimulation (TMS) can be used to study excitability of corticospinal neurons in human motor cortex. It is currently not fully elucidated if corticospinal neurons in the hand vs. leg representation show the same or different regulation of their excitability by GABAAergic and glutamatergic interneuronal circuitry. Using a paired-pulse TMS protocol we tested short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) in 18 healthy participants. Motor evoked potentials were evoked in one hand (abductor digiti minimi) and one leg muscle (tibialis anterior), with systematic variation of the intensities of the first (S1) and second (S2) pulse between 60 and 140% resting motor threshold (RMT) in 10% steps, at two interstimulus intervals of 1.5 and 2.1 ms. For the hand and leg motor representations and for both interstimulus intervals, SICI occurred if the intensities of S1 < RMT and S2 > RMT, while SICF predominated if S1 = S2 ≤ RMT, or S1 > RMT and S2 < RMT. Findings confirm and extend previous evidence that the regulation of excitability of corticospinal neurons of the hand versus leg representation in human primary cortex through GABAAergic and glutamatergic interneuronal circuits is highly similar, and that corticospinal neurons of both representations are activated by TMS transsynaptically in largely identical ways.

Protocol of transcranial magnetic stimulation and photobiomodulation integration

Protocol of transcranial magnetic stimulation and photobiomodulation integration

ArTGen: An Arduino-based trigger generator to remotely handle pulse timing in TMS units

Abstract Introduction: Transcranial magnetic stimulation (TMS) protocols are associated with specific combinations of stimulation parameters, including the location of the targeted site, E-field intensity and orientation, pulse shape and duration, variable/fixed inter-pulse interval (IPI), and coil shape and dimension. Among these parameters, IPI may significantly affect the direction of induced neuroplasticity and the possible interference of habituation and expectation effects with TMS-evoked potentials. The TMS units are not always flexible enough to generate customized pulse sequences, thus external devices/software are commonly used. To remotely handle the randomization of IPI, we designed an effective and cheap device (ArTGen – Arduino Uno-based Trigger Generator) for generating arbitrary sequences of square-wave digital pulses. Materials and methods: Using an external foot-switch pedal the TMS experimenter is able to handle the ArTGen’s firmware to remotely drive a customized sequence of pulses in the TMS unit. We designed the firmware to switch among four conditions (single pulse, sequence of jittered pulses, pause and stop) based on a single and double foot-switch taping. We used two BNC sockets to manage respectively the foot-switch signal and the randomized TTLs in output to ArTGen. We tested ArTGen on Magstim Rapid2 with AirFilm® figure-8 coil in tasks with the following characteristics: (i) %Maximal Stimulation Output at 50%; (ii) 100 pulses and (iii) central pulse frequencies set to either 0.1, 5, 10, 15, or 20 Hz. Results: Our results show that all the TTLs released by ArTGen were correctly detected by Magstim Rapid2, and highlight a short delay (computed as the difference between the Arduino trigger and the Magstim Rapid2 output) of about 5μsec across all pulse frequencies. Conclusion: ArTGen is a stand-alone, portable, and not cumbersome opensource device used to randomize TMS pulses or to trigger/synchronize different devices in a closed-loop TMS system with microseconds of accuracy. Keywords: TMS unit, Arduino board, Inter Pulse Interval randomization, Closed Loop TMS System Synchronization

Multi-target repetitive transcranial magnetic stimulation (rTMS) protocol for the treatment of comorbid depression and chronic pain

Abstract Background: Major Depressive Disorder (MDD) and chronic pain are frequently co-occurring, and the onset of either condition can either precede or follow the onset of the other. Notably, clinical outcome for pharmacological and rTMS treatment for depression is significantly worse in the presence of chronic pain symptoms. To improve clinical care for depression it is thus critical to address the comorbidity of depression and chronic pain in a unified approach rather than treating them as separate conditions. Objective: We examined whether a multi-target rTMS protocol including stimulation of the left dorsolateral prefrontal cortex (DLPFC) and primary motor cortex (M1) would improve depressive and chronic pain symptoms more than a standard single-target rTMS protocol. Methods: We treated 20 comorbid depressive and chronic pain patients with a multi-target rTMS protocol and another 20 age- and sex-matched comorbid patients that had comparable baseline depression and pain symptom severity were treated only at the left DLPFC, for a minimum of 10 sessions. We have also recorded electroencephalography (EEG) at baseline session and examined a previously reported metric of pain sensitivity, peak alpha frequency (PAF), as a possible marker of treatment outcome. Preliminary Results: The multi-target rTMS achieved on average 15% greater improvement than stimulation at left DLPFC alone. Cohen’s D effect size was D = 0.8, which represents a moderate effect. We will also present EEG data examining the associations between PAF and pain and depression treatment outcomes. Conclusions: Multi-target rTMS to DLPFC and M1 may be more effective in treating the comorbidity of depression and chronic pain than rTMS to DLPFC only. Multi-site protocols could represent a treatment augmentation strategy with significant benefit for comorbid subjects. Other potential rTMS target site should be evaluated in future studies. Keywords: Chronic Pain, Depression, EEG, TMS

Effects of lower limb segmental muscle vibration on primary motor cortex short-latency intracortical inhibition and spinal excitability in healthy humans.

We examined the effects of lower limb segmental muscle vibration (SMV) on intracortical and spinal excitability in 13 healthy participants (mean age: 34.9 ± 7.8years, 12 males, 1 female). SMV at 30Hz was applied to the hamstrings, gastrocnemius, and soleus muscles for 5min. Paired-pulse transcranial magnetic stimulation protocols were used to investigate motor-evoked potential(MEP) amplitude, short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) from the abductor hallucis muscle (AbdH). These assessments were compared to the results of a control experiment (i.e., non-vibration) in the same participants. F-waves were evaluated from the AbdH on the right (vibration side) and left (non-vibration side) sides, and we calculated the ratio of the F-wave amplitude to the M-response amplitude (F/M ratio). These assessments were obtained before, immediately after, and 10, 20, and 30min after SMV. For SICI, there was no change immediately after SMV, but there was a decrease over time (before vs. 30min after, p = 0.021; immediately after vs. 30min after, p = 0.015). There were no changes in test MEP amplitude, SICF, or the F/M ratio. SMV causes a gradual decrease in SICI over time perhaps owing to long-term potentiation. The present results may have implications for the treatment of spasticity.

Causal decoding of individual cortical excitability states

Brain responsiveness to stimulation fluctuates with rapidly shifting cortical excitability state, as reflected by oscillations in the electroencephalogram (EEG). For example, the amplitude of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) of motor cortex changes from trial to trial. To date, individual estimation of the cortical processes leading to this excitability fluctuation has not been possible.Here, we propose a data-driven method to derive individually optimized EEG classifiers in healthy humans using a supervised learning approach that relates pre-TMS EEG activity dynamics to MEP amplitude. Our approach enables considering multiple brain regions and frequency bands, without defining them a priori, whose compound phase-pattern information determines the excitability.The individualized classifier leads to an increased classification accuracy of cortical excitability states from 57% to 67% when compared to μ-oscillation phase extracted by standard fixed spatial filters. Results show that, for the used TMS protocol, excitability fluctuates predominantly in the μ-oscillation range, and relevant cortical areas cluster around the stimulated motor cortex, but between subjects there is variability in relevant power spectra, phases, and cortical regions. This novel decoding method allows causal investigation of the cortical excitability state, which is critical also for individualizing therapeutic brain stimulation.

Theta burst deep TMS for the treatment of major depression

Background: Intermittent theta burst stimulation (iTBS) is a promising transcranial magnetic stimulation (TMS) protocol that can induce neuroplastic changes in short stimulation time and was FDA-cleared recently for MDD. Deep TMS (dTMS) enables activation of deeper and broader brain volume, and with high frequency (HF) protocol was found to be highly effective in MDD. This study investigates dTMS with iTBS in MDD.Methods: 69 MDD patients received dTMS iTBS treatment at a clinical setting, composed of bursts of 3 pulses at 50 Hz, 5 Hz burst frequency, 2s on and 8 s off, 1800 pulses per session. The primary endpoint was the change from baseline in HDRS-21 scores after 4-weeks (20 treatment sessions). Secondary endpoints included response and remission rates based on HDRS-21 scores, after 4-weeks and 6-weeks (30 sessions), change in CGI-S score from baseline to 6-weeks and response and remission rates based on CGI-S scores at the 6-week visit.Results: The treatment was well-tolerated with no adverse events. The mean HDRS-21 change from baseline to week 4 was -9.82 (p<0.0001), and to week 6 was -11.91 (p<0.0001). Response and remission rates based on HDRS-21 after 4 weeks were 51.5% and 52.9%, respectively, and after 6 weeks (were 81.4% and 76.3%, respectively. The mean CGI-S change from baseline to week 6 was -2.91 (p<0.0001). Response and remission rates after 6 weeks based on CGI-S were 79.3% and 67.2%, respectively.Conclusions: Deep TMS iTBS was found to be a safe and highly effective treatment alternative for major depression.Conflicts of Interests: Dr. Roth and Dr. Zangen are key inventors of deep TMS technology and have financial interest in BrainsWay. Dr. Tendler serves as the chief medical officer of and has a financial interest in BrainsWay, and he has ownership interest in Advanced Mental Health Care, Inc. Dr. Pell and Dr. Zibman are BrainsWay employees.Funding: This work was supported by BrainsWay Ltd. Background: Intermittent theta burst stimulation (iTBS) is a promising transcranial magnetic stimulation (TMS) protocol that can induce neuroplastic changes in short stimulation time and was FDA-cleared recently for MDD. Deep TMS (dTMS) enables activation of deeper and broader brain volume, and with high frequency (HF) protocol was found to be highly effective in MDD. This study investigates dTMS with iTBS in MDD. Methods: 69 MDD patients received dTMS iTBS treatment at a clinical setting, composed of bursts of 3 pulses at 50 Hz, 5 Hz burst frequency, 2s on and 8 s off, 1800 pulses per session. The primary endpoint was the change from baseline in HDRS-21 scores after 4-weeks (20 treatment sessions). Secondary endpoints included response and remission rates based on HDRS-21 scores, after 4-weeks and 6-weeks (30 sessions), change in CGI-S score from baseline to 6-weeks and response and remission rates based on CGI-S scores at the 6-week visit. Results: The treatment was well-tolerated with no adverse events. The mean HDRS-21 change from baseline to week 4 was -9.82 (p<0.0001), and to week 6 was -11.91 (p<0.0001). Response and remission rates based on HDRS-21 after 4 weeks were 51.5% and 52.9%, respectively, and after 6 weeks (were 81.4% and 76.3%, respectively. The mean CGI-S change from baseline to week 6 was -2.91 (p<0.0001). Response and remission rates after 6 weeks based on CGI-S were 79.3% and 67.2%, respectively. Conclusions: Deep TMS iTBS was found to be a safe and highly effective treatment alternative for major depression. Conflicts of Interests: Dr. Roth and Dr. Zangen are key inventors of deep TMS technology and have financial interest in BrainsWay. Dr. Tendler serves as the chief medical officer of and has a financial interest in BrainsWay, and he has ownership interest in Advanced Mental Health Care, Inc. Dr. Pell and Dr. Zibman are BrainsWay employees. Funding: This work was supported by BrainsWay Ltd.

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation.

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short- and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short- and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single- and paired-pulse TMS measurements. A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single- and paired-pulse TMS protocols. This paper shows how to record a number of single- and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS.

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short- and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short- and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single- and paired-pulse TMS measurements. A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single- and paired-pulse TMS protocols. This paper shows how to record a number of single- and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS.

Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study

ObjectiveHepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. Methods23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. ResultsMEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. ConclusionsOur study revealed reduced synaptic plasticity of the primary motor cortex in HE. SignificanceReduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients.

5-day multi-session intermittent theta burst stimulation over bilateral posterior superior temporal sulci in adults with autism-a pilot study

BackgroundTheta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. MethodsIn this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. ResultsThe results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. ConclusionsGiven the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.