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Highlights • Cerebral hemodynamics of non-invasive brain stimulation using TCD is less explored. • Cerebral blood flow velocity changes in response to rTMS and tDCS. • Need for a more standardized approach with future studies. Abstract Objective Non-invasive brain stimulation (NIBS), such as repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS), are promising neuromodulatory priming techniques to promote task-specific functional recovery after stroke. Despite promising results, clinical application of NIBS has been limited by high inter-individual variability. We propose that there is a possible influence of neuromodulation on cerebral blood flow (CBF), as neurons are spatially and temporally related to blood vessels. Transcranial Doppler (TCD), a clinically available non-invasive diagnostic tool, allows for evaluation of CBF velocity (CBFv). However, little is known about the role of neuromodulation on CBFv. Methods A systematic review of literature to understand the effects of NIBS on CBFv using TCD in stroke was conducted. Results Twelve studies fit our inclusion criteria and are included in this review. Our review suggested that CBFv and/or vasomotor reactivity maybe influenced by rTMS dosage (intensity and frequency) and the type of tDCS electrode montage. Conclusion There is limited evidence regarding the effects of NIBS on cerebral hemodynamics using TCD and the usefulness of TCD to capture changes in CBFv after NIBS is not evident from this review. We highlight the variability in the experimental protocols, differences in the applied neurostimulation protocols and discuss open questions that remain regarding CBF and neuromodulation. Significance TCD, a clinically accessible tool, may potentially be useful to understand the interaction between cortical neuromodulation and CBFv. [ABSTRACT FROM AUTHOR]

• This comparative study included subjects with opioid use disorder to evaluate the effect of iTBS-MMT combination therapy. • Subjects in the iTBS-MMT group had significant improvement in anxiety, depression and craving reduction. • No serious adverse events were observed during treatment. Prior studies indicate that subjects undergoing methadone maintenance therapy (MMT) may experience anxiety, depression and cravings. This study aimed to explore the impact of intermittent theta burst stimulation (iTBS)-MMT combination on craving and emotional symptoms of opioid use disorder. This comparative study included subjects with opioid use disorder at the Methadone Maintenance Clinic of Pudong New Area between September 2019 and March 2020. The subjects were divided into two groups: those who received iTBS-MMT combination treatment (iTBS-MMT) and those who received MMT treatment and sham stimulation treatment (MMT). Outcomes were reduction rate of anxiety, depression and craving. Anxiety was measured by Hamilton Anxiety (HAMA) scale, depression was determined by Hamilton Depression (HAMD) scale and craving was analyzed using visual analog scale. A total of 76 subjects completed the treatment, with 38 subjects in each group. Twenty days after treatment, subjects in the iTBS-MMT group had significant improvement of anxiety (HAMA reduction rate), depression (HAMD reduction rate) and craving (Craving reduction rate) reduction rate compared with MMT group. iTBS-MMT combination treatment may produce better drug craving reduction and emotional improvement than MMT alone. [ABSTRACT FROM AUTHOR]

Objective: Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Methods: Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Results: Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. Conclusion: These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

Among the most prevalent psychiatric conditions stand anxiety and depression. Psychotherapy and medications are considered effective treatments in these clinical settings. However, pharmacotherapy and psychotherapy (i.e., cognitive behavioral therapy (CBT)) administered in monotherapy or in a combined regimen do not result in satisfactory outcomes in all patients. Therefore, finding new treatments would be of great help. In the last three decades, noninvasive brain stimulation (NIBS) has emerged as a safe tool to improve several neuropsychiatric symptoms. The following work revisits the available reports that assessed the add-on value of NIBS techniques when combined to psychotherapy (CBT or related interventions) in mood and anxiety disorders. The available protocols targeted the prefrontal cortex, a region that was previously found to have an enhanced activity or functional connectivity after psychotherapeutic interventions. Promising yet scarce evidence exists on this matter. A discrepancy exists among the available reports regarding the type and duration of interventions, the patients’ clinical profiles, and the presence of a sham intervention. NIBS may have acted by enhancing psychotherapy effects on the top-down cognitive control of emotions. Combining both therapies may result in promising effects, but future large-scale trials are needed to judge the utility of this combination in psychiatric populations.

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30 min daily for 10 days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury + stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury. [ABSTRACT FROM AUTHOR]

Background Polarising currents can modulate membrane potentials in animals, affecting the after-effect of theta burst stimulation (TBS) on synaptic strength. Objective We examined whether a similar phenomenon could also be observed in human motor cortex (M1) using transcranial direct current stimulation (TDCS) during monophasic intermittent TBS (iTBS). Methods TDCS was applied during posterior-anterior iTBS using three different conditions: posterior-anterior TDCS (anode 3.5 cm posterior to M1, cathode 3.5 cm anterior to M1), anterior-posterior TDCS (cathode 3.5 cm posterior to M1, anode 3.5 cm anterior to M1), and sham TDCS. Results When the direction of TDCS (posterior-anterior) matched the direction of the electrical field induced by iTBS, we found a 19% non-significant increase in excitability changes in comparison with iTBS combined with sham TDCS. When the TDCS was reversed (anterior-posterior), the excitatory effect of iTBS was abolished. Conclusion Our findings suggest that excitatory after-effects of iTBS can be modulated by directionally-specific TDCS. [ABSTRACT FROM AUTHOR]

Purpose: Spasticity is a common disorder in patients with spinal cord injury (SCI). The aim of this study was to investigate whether intermittent theta burst stimulation (iTBS), a safe, non-invasive and well-tolerated protocol of excitatory repetitive transcranial magnetic stimulation (rTMS), is effective in modulating spasticity in SCI patients. Methods: In this randomized, double-blind, crossover, sham-controlled study, ten subjects with incomplete cervical or thoracic SCI received 10 days of daily sessions of real or sham iTBS. The H/M amplitude ratio of the Soleus H reflex, the amplitude of the motor evoked potentials (MEPs) at rest and during background contraction, as well as Modified Ashworth Scale (MAS) and the Spinal Cord Injury Assessment Tool for Spasticity (SCAT) were compared before and after the stimulation protocols. Results: Patients receiving real iTBS showed significant increased resting and active MEPs amplitude and a significant reduction of the H/M amplitude ratio. In these patients also the MAS and SCAT scores were significantly reduced after treatment. These changes persisted up to 1 week after the end of the iTBS treatment, and were not observed under the sham-TBS condition. Conclusion: These findings suggest that iTBS may be a promising therapeutic tool for the spasticity in SCI patients. [ABSTRACT FROM AUTHOR]

Background: Intermittent theta burst stimulation (iTBS) of the primary motor cortex improves transiently lower limbs spasticity in multiple sclerosis (MS). However, the cerebral mechanisms underlying this effect have never been investigated. Objective: To assess whether modulation of spasticity induced by iTBS is underlined by functional reorganization of the primary motor cortices. Methods: A total of 17 patients with MS suffering from lower limbs spasticity were randomized to receive real iTBS or sham iTBS during the first half of a 5-week indoor rehabilitation programme. Spasticity was assessed using the Modified Ashworth Scale and the Visual Analogue Scale at baseline, after the stimulation session and at the end of the rehabilitation programme. Resting-state functional magnetic resonance imaging (fMRI) was performed at the three time points, and brain functional networks topology was analysed using graph-theoretical approach. Results: At the end of stimulation, improvement of spasticity was greater in real iTBS group than in sham iTBS group (p = 0.026). iTBS had a significant effect on the balance of the connectivity degree between the stimulated and the homologous primary motor cortex (p = 0.005). Changes in inter-hemispheric balance were correlated with improvement of spasticity (rho = 0.56, p = 0.015). Conclusion: This longitudinal resting-state fMRI study evidences that functional reorganization of the primary motor cortices may underlie the effect of iTBS on spasticity in MS. [ABSTRACT FROM AUTHOR]

• This is the first randomized, double-blind, and sham-controlled trial to simultaneously focus on the use of accelerated iTBS for social cognition and negative symptoms among individuals with schizophrenia. • Accelerated iTBS can effectively ameliorate the social cognition and negative symptoms of individuals with schizophrenia. • The Accelerated iTBS may be a safe and well-tolerated neuromodulation technology to individuals with schizophrenia, and has a good clinical application prospect. Social cognitive and negative symptoms impairment may increase the risk of mental disability in individuals with schizophrenia. However, randomized controlled studies on the effectiveness of accelerated intermittent theta burst stimulation (iTBS) for social cognition and negative symptoms in individuals with schizophrenia are very limited. A total of 125 individuals with schizophrenia were recruited, 66 of whom were randomly divided into an active iTBS group (n=34) and sham iTBS group (n=32) by stratified sampling. Participants received either active iTBS or sham iTBS targeting the left dorsolateral prefrontal cortex (DLPFC) 20 sessions for 4 weeks under navigation. The Facial Emotion Recognition Test (FERT), Hinting Task (HT), and Positive and Negative Syndrome Scale (PANSS) were measured at baseline, 2 weeks, and 4 weeks. The trial protocol was registered with the Chinese Clinical Trial Registry (ChiCTR2100051984). Sixty patients (90.90%) completed the intervention and the 4-week follow-up, including 29 women (43.94%) and 37 men (56.06%) with a mean (SD) age of 47.53 (10.17) years. The primary outcomes showed FERT scores (week 2; 0.27 [95% CI, 0.09 to 0.45]; P <.01; ES 0.14) (week 4; 0.63 [95% CI, 0.45 to 0.80]; P <.001; ES 0.47) and HT scores (week 2; 1.00 [95% CI, -0.02 to 1.98]; P <.05; ES 0.67) (week 4; 2.13 [95% CI, 1.21 to 3.06]; P <.001; ES 0.27) in the active iTBS group were significantly different from those in the sham iTBS group at 2 and 4 weeks of follow-up. The secondary outcome showed that the negative symptom score (-3.43 [95% CI, -4.85 to -2.01]; P <.001; ES 0.29) of the active iTBS group was significantly different from that of the sham iTBS group at the 4th week of follow-up. Accelerated iTBS can effectively ameliorate the social cognition and negative symptoms of individuals with schizophrenia. These results suggest that accelerated iTBS may be a safe and effective neuromodulation technique to improve the overall functional recovery of individuals with schizophrenia, and has a good clinical application prospect. [ABSTRACT FROM AUTHOR]

It has been hypothesized that intermittent theta burst stimulation (iTBS) can produce a memory-enhancing effect by inducing long-term potentiation (LTP)-like plasticity in the dorsolateral prefrontal cortex (DLPFC). However, the hemispheric difference by which iTBS modulates working memory in healthy adults has not been well investigated. The objective of the present study is to investigate the effects of iTBS on the left dorsolateral prefrontal cortex (LDLPFC) and right dorsolateral prefrontal cortex (RDLPFC) on working memory performance in healthy adults. In this randomized cross-over experiment, 31 right-hand dominant healthy adults received a single-session of iTBS to their LDLPFC, RDLPFC and sham stimulation, in three different visits separated by a seven-day waiting period. Working memory capacity was assessed before and immediately after stimulation, by using 2-and 3-back tasks. After stimulation, significant time effects were found in overall accuracy when performing both 2- (p = 0.013) and 3-back tasks (p = 0.027), as well as the total reaction time during 3-back tasks (p = 0.021). Analysis of secondary outcomes showed an increase in the number of correction rejections in 2-back tasks (p = 0.009). However, all of the time-by-group interaction effects were not significant. This experiment did not find any additional memory-enhancing effects with a single-session of iTBS to either the RDLPFC or the LDLPFC in healthy adults beyond the practice effects. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (TMS) is of two types, including continuous theta-burst stimulation (cTBS) and intermittent theta-burst stimulation (iTBS), which is currently applied in various neuropsychiatric disorders. This study aimed to explore the effect of cTBS and iTBS on hypertension and the mechanism using male spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat models. Norepinephrine and epinephrine levels were determined using enzyme immunoassay kits. About 60, 80, and 100% of the motor threshold were used for stimulation. The systolic blood pressure (SBP; 168 ± 3 vs. 189 ± 3 mmHg), diastolic blood pressure (DBP; 134 ± 5 vs. 158 ± 4 mmHg), and mean artery pressure (MAP; 146 ± 3 vs. 170 ± 3 mmHg) were attenuated after cTBS (100%) stimulation on T4 of male SHR. The SBP (165 ± 4 vs. 189 ± 3 mmHg), DBP (136 ± 4 vs. 159 ± 2 mmHg), and MAP (146 ± 3 vs. 169 ± 2 mmHg) were alleviated after cTBS (100%) stimulation on L2. The blood pressure was also attenuated after iTBS (100%) stimulation on T4 or L2 of male SHR. The stimulation of cTBS or iTBS on S2 spinal column did not affect the blood pressure of male SHR rats. The stimulation of cTBS or iTBS has no effect on the blood pressure in male WKY rats. Norepinephrine and epinephrine levels in the male SHR rat kidneys were reduced after cTBS or iTBS stimulation on T4 and L2. These results indicated that TMS attenuates hypertension after spinal column stimulation via reduction of catecholamines. Thus, treatment with TMS may be a strategy for hypertension therapy in the future. NEW & NOTEWORTHY Repetitive transcranial magnetic stimulation (TMS) is currently applied in various neuropsychiatric disorders. The aim of this study was to explore the effect of TMS on hypertension and its mechanism. We found TMS attenuates hypertension after T4 or L2 spinal column stimulation via reduction of catecholamines in male spontaneously hypertensive rat. Treatment with TMS may be a strategy for hypertension therapy in the future.

Objective: This study aims to investigate the longer-term effects of accelerated intermittent theta burst stimulation (aiTBS) in smoking cessation and to examine whether there is a difference in outcome between active and placebo stimulation. The present study constitutes an ancillary study from a main Randomized Controlled Trial (RCT) evaluating the acute effects of aiTBS in smoking reduction., Method: A double-blind randomized control trial was conducted where 89 participants were randomly allocated to three groups (transcranial magnetic stimulation (TMS)&N group: active aiTBS stimulation combined with neutral videos; TMS&S group: active aiTBS stimulation combined with smoking-related videos; Placebo group: placebo stimulation combined with smoking-related videos). Nicotine dependence, tobacco craving, perceived stress and motivation to quit smoking were measured after completion of 20 aiTBS sessions and during various follow ups (post one week, post one month and post six months)., Results: Our results show that the positive effect on nicotine dependence and tobacco craving that occurred at the end of treatment lasts at least one month post treatment. This effect seems to dissipate six months post treatment. No significant differences were found between the three groups., Conclusion: Both active and placebo stimulation were equally effective in reducing nicotine dependence and tobacco craving up to one month after the end of treatment., Competing Interests: None., (© 2022 The Author(s).)

Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro . Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n = 9 cells from 7 animals) or sham ( n = 10 cells from 9 animals), immediately after stimulation, as well as 10 and 20 min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20 min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20 min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. [ABSTRACT FROM AUTHOR]

A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n = 41 participants with spider phobia and n = 42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further. [ABSTRACT FROM AUTHOR]

Objective: Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Methods: Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Results: Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. Conclusion: These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted. [ABSTRACT FROM AUTHOR]

The study assumed that the antisaccade (AS) task is a relevant psychophysical tool to assess (i) short-term neuromodulation of the dorsolateral prefrontal cortex (DLPFC) induced by intermittent theta burst stimulation (iTBS) and (ii) mood change occurring during the course of the treatment. Saccadic inhibition is known to strongly involve the DLPFC, whose neuromodulation with iTBS requires less stimulation time and lower stimulation intensity, as well as results in longer aftereffects than the conventional repetitive transcranial magnetic stimulation (rTMS). Active or sham iTBS was applied every day for three weeks over the left DLPFC of 12 drug-resistant bipolar depressed patients. To assess the iTBS-induced short-term neuromodulation, the saccadic task was performed just before (S1) and just after (S2) the iTBS session, the first day of each week. Mood was evaluated through MADRS scores and the difference in scores between the beginning and the end of treatment was correlated with AS performance change between these two periods. As expected, only patients from the active group improved their performance from S1 to S2 and mood improvement was significantly correlated with AS performance improvement. In addition, the AS task also discriminated depressive bipolar patients from healthy control subjects. Therefore, the AS task could be a relevant and useful tool for clinicians to assess if the TMS-induced short-term neuromodulation of the DLPFC occurs as well as a ‘trait vs. state’ objective marker of depressive mood disorder.

Motor preparatory and execution activity is enhanced after a single session of bimanual visuomotor training (BMT). Recently, we have shown that increased primary motor cortex (M1) excitability occurs when BMT involves simultaneous activation of homologous muscles and these effects are enhanced when BMT is preceded by intermittent theta burst stimulation (iTBS) to the left dorsal premotor cortex (lPMd). The neural mechanisms underlying these modulations are unclear, but may include interhemispheric interactions between homologous M1s and connectivity with premotor regions. The purpose of this study was to investigate the possible intracortical and interhemispheric modulations of the extensor carpi radials (ECR) representation in M1 bilaterally due to: (1) BMT, (2) iTBS to lPMd, and (3) iTBS to lPMd followed by BMT. This study tests three related hypotheses: (1) BMT will enhance excitability within and between M1 bilaterally, (2) iTBS to lPMd will primarily enhance left M1 (lM1) excitability, and (3) the combination of these interventions will cause a greater enhancement of bilateral M1 excitability. We used single and paired-pulse transcranial magnetic stimulation (TMS) to quantify M1 circuitry bilaterally. The results demonstrate the neural mechanisms underlying the early markers of rapid functional plasticity associated with BMT and iTBS to lPMd primarily relate to modulations of long-interval inhibitory (i.e. GABA B -mediated) circuitry within and between M1s. This work provides novel insight into the underlying neural mechanisms involved in M1 excitability changes associated with BMT and iTBS to lPMd. Critically, this work may inform rehabilitation training and stimulation techniques that modulate cortical plasticity after brain injury. [ABSTRACT FROM AUTHOR]

Smoking is among the leading causes of mortality worldwide. Discontinuing smoking can increase life expectancy to the presmoking level. Unaided attempts are often ineffective, strengthening the necessity of cognitive-behavioral therapy (CBT), nicotine replacement or pharmacotherapy. Still, relapse rates are high. Recently, a modulation of nicotine craving, which predicts relapse, through transcranial magnetic stimulation to the prefrontal cortex was shown. In a pilot study, we investigated whether 4 sessions of intermittent theta burst stimulation (iTBS) as add-on treatment to CBT reduces nicotine craving and improves long-term abstinence (at 3, 6 and 12 months). Smokers were randomly assigned to a treatment (n = 38) or a sham group (n = 36). Although we did not find reduced craving, we could show higher abstinence rates in the treatment group at 3 months. At 6 and 12 months abstinence rates did not differ significantly. Results at 12 months, however, have to be interpreted cautiously due to significant differences in the dropout rates between the two groups at this time point. We provide first evidence for a beneficial effect of additional iTBS on intermediate nicotine abstinence; however, the low number of iTBS sessions might have prevented longer effects. More lasting effects might be achieved by iTBS maintenance sessions in analogy to the treatment of depression. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Previous studies have found that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellar hemisphere could improve swallowing function, but whether intermittent theta burst stimulation (iTBS), which has similar excitatory effect and higher efficiency, can also improve swallowing function for dysphagia after stroke remains unclear., Objective: This trial aimed to explore the efficacy and safety of bilateral cerebellar transcranial magnetic stimulation with iTBS for dysphagia after stroke., Methods: Seventy patients with dysphagia after stroke were divided into 2 treatment groups: true bilateral cerebellar iTBS and sham bilateral cerebellar iTBS. The true iTBS group underwent ten 100% resting motor threshold (RMT) iTBS sessions for 2 weeks. In the sham iTBS group, the parameters were the same except that the figure-eight coil was perpendicular to the skull. Both groups received traditional swallowing rehabilitation treatment 5 times a week for 2 weeks. Swallowing function was assessed with the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), Penetration/Aspiration Scale (PAS), Standardized Swallowing Assessment (SSA), and Functional Oral Intake Scale (FOIS) at baseline, 2 weeks after the intervention, and at 4 weeks of follow-up., Results: There were significant time and group interaction effects in both multi-factorial adjusted and unadjusted FEDSS, PAS, SSA, and FOIS score ( P < .001). In the pairwise comparison of the swallowing parameters among the 2 groups, the FEDSS, PAS, SSA, and FOIS scores at 2 weeks and 4 weeks showed a significantly higher improvement in the iTBS simulation group than sham group ( P < .05). In both the true iTBS and sham iTBS stimulation groups, all FEDSS, PAS, SSA, and FOIS scores were significantly improved over time ( P < .001)., Conclusions: The present study suggested that as a more efficient TMS stimulation mode, iTBS could efficiently improve swallowing function by stimulating the bilateral cerebellar hemisphere. In addition, 100% resting motor threshold bilateral cerebellar iTBS is a relatively safe treatment., Clinical Trial Registration: Effect analysis of repeated transcranial magnetic stimulation of cerebellar on dysphagia after stroke. www.chictr.org.cn. Identifier: ChiCTR2100042092.

Upper limb weakness and incoordination is a common disability following ischemic stroke. Previous studies have showed that the single application of external counterpulsation (ECP) and intermittent theta burst stimulation (iTBS) can effectively enhance the cortical motor excitability and facilitate recovery. However, it remains uncertain if sequential application of these therapies would further augment the recovery. We hypothesize a synergistic effect of ECP followed by iTBS to upper limb function may happen through improvements in both cerebral perfusion and neuron excitability. [ABSTRACT FROM AUTHOR]

Previous work noted that there are significant variabilities in motor response to intermittent theta-burst stimulation (iTBS). It is possible this variability results from individual neuroanatomical differences. The current objective was to investigate the effect of individual neuroanatomy on first dorsal interosseous (FDI) and biceps brachii motor evoked potentials (MEPs) in response to iTBS. Cross-sectional study using a convenience sample. Research laboratory. Ten healthy individuals (7 females, 23.5 ± 5 years) participated in this study. Participants completed two iTBS sessions (one each targeting the FDI and biceps cortical hotspots) and an MRI on separate days. Not applicable. MEPs were calculated using data acquired with a Magstim Super Rapid2 Plus1 stimulator via a 70 mm double air film coil to the primary motor cortex and electromyography signals were measured from dominant FDI and biceps. Head models were generated from T1 & T2 weighted MRI. Diffusion tensor imaging was used to determine fiber tract geometry for FDI and biceps corticospinal tracts. We then established neuroanatomical parameters including: fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD). Cortical electric field strength (EFS) was calculated using simulated stimulation of head models and finite element analysis. For the FDI, there was no effect of iTBS (p = 0.223) but individual changes in corticomotor excitability scaled with stimulation type and resting motor potential (p < 0.001), EFS (p = 0.001), BSD (p = 0.004), and FTSA (p = 0.011). iTBS had a faciliatory response on the biceps and was dependent on FTSA (p < 0.001) and TFC (p < 0.001). Our results show that MRI-based measures of neuroanatomy, specifically cortical architecture and tract anatomy, impact how the motor system responds to iTBS, subject to target-specific cortical control organization. MRI-based modeling of individual neuroanatomy may be a useful approach in selection of motor targets when designing iTBS-based therapies. None. [ABSTRACT FROM AUTHOR]

Background: Currently available medication for Alzheimer's disease (AD) slows cognitive decline only temporarily but has failed to bring about long term positive effects. For this slowly progressive neurodegenerative disease, so far, no disease modifying therapy exists., Objective: The study aims to find out if non-pharmacologic non-invasive neuromodulatory repetitive transcranial magnetic stimulation (rTMS) may offer a new alternative or an add on therapeutic strategy against loss of cognitive functions., Methods: In this exploratory intervention study, safety and symptom development before and after frontopolar cortex stimulation (FPC) using intermittent theta burst stimulation (iTBS) at 10 subsequent working days was monitored as add-on treatment in 28 consecutive patients with AD. Out of these, 10 randomly selected patients received sham stimulation as a control. Serum concentrations of neurotransmitter precursor amino acids, immune activation and inflammation markers, brain-derived neurotrophic factor (BDNF), and nitrite were measured., Results: Treatment was well tolerated, and no serious adverse effects were observed. Improvement of cognition was detected by an increase in Mini Mental State Examination score (MMSE; p<0.01, paired rank test) and also by an increase in a modified repeat address phrase test, part of the 6-item cognitive impairment test (p<0.01). A trend to increase the clock drawing test (CDT; p = 0.08) was also found in the verum treated group. Furtheron, in 10 of the AD patients with additional symptoms of depression treated with iTBS, a significant decrease in the HAMD-7 scale (p<0.01) and a trend to lower serum phenylalanine concentrations (p = 0.08) was seen. No changes in the parameters tested were found in the sham treated patients., Conclusion: Our preliminary results may indicate that iTBS is effective in the treatment of AD. Also a slight influence of iTBS on the metabolism of phenylalanine was found after 10 iTBS sessions. An impact of iTBS to influence the enzyme phenylalanine hydroxylase (PAH), as found in the previous series of treatment resistant depression, could not be seen in our first observational trial in 10 AD patients with comorbidity of depression. Longer treatment periods for several weeks in a higher number of AD patients with depression could cause more intense and disease modifying effects visible in different neurotransmitter concentrations important in the pathogenesis of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment. Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls. Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively. Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Mu, Ren, Tang, Wei, Wang, Song, Zhu, Ling, Gao, Zhang, Song, Wei, Chang, Wei, Wang, Zhao, Wang, Liu, Zhou, Zhou, Xu and Jiao.)

Background. Evidence remains mixed as to the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in treating mild cognitive impairment (MCI) in patients with Parkinson's disease (PD). Objective. In this study, we examined the short- and long-term effects of patterned rTMS. Methods. We randomly assigned 35 patients with PD with MCI to two groups. One group received intermittent theta burst stimulation (iTBS; n = 20), and the other received its sham counterpart (n = 15). The stimulations were applied over the left dorsolateral prefrontal cortex for 10 consecutive weekdays. Measurements based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Montreal Cognitive Assessment (MoCA) were conducted at three time points: at baseline, immediately after the last intervention and at 3-month follow-up. Each patient received a 99mTc-TRODAT-1 single-photon emission computed tomography (SPECT) brain scan at baseline. Results. The iTBS group exhibited significantly greater improvement than the sham group did in total RBANS and MoCA scores ( p < .001 for both) immediately after intervention and at the 3-month follow-up. Radiotracer uptake in the bilateral basal ganglion in baseline SPECT was positively correlated with response to iTBS conditioning with respect to improvements in MoCA scores ( p = .021). Conclusion. This randomised controlled trial provides evidence that a consecutive iTBS protocol can achieve a persistent and wide-ranging therapeutic effect in patients with PD with MCI.

Neuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD). Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, the objective of this proof-of-concept study was to investigate the safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD. Six subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. The FMD symptom severity was assessed at baseline, during treatment and 24 h after the last iTBS session. Multiple doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a marked reduction in FMD symptom severity. Corticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research. [ABSTRACT FROM AUTHOR]