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Non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), and transcranial direct current stimulation (tDCS), is an emerging intervention that has been used to treat various mental illnesses. However, previous studies have not comprehensively compared the efficacies of various NIBS modalities in alleviating anxiety symptoms among patients with generalized anxiety disorder (GAD). Therefore, this study conducted a systematic review and meta-analysis to assess the efficacy of NIBS for patients with GAD. A systematic search of four major bibliographic databases (Embase, PubMed, Web of Science and The Cochrane Library) was conducted from inception dates to November 26, 2023 to identify eligible studies. The data were analyzed using a random-effects model. Seven randomized controlled trials (RCTs) were included in the meta-analysis. Significant differences were found in changes in Hamilton anxiety rating scale (HARS) scores, study-defined response, and remission between the intervention and control groups. Moreover, the intervention groups experienced a significantly higher frequency of headaches. The results revealed that interventions improved GAD compared to control groups. cTBS and rTMS exhibited better treatment efficacy than tDCS, which did not appear to have a significant therapeutic effect. Longer follow-up periods and larger sample sizes are required in future RCTs. This meta-analysis was conducted in accordance with PRISMA guidelines and registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/ , CRD42023466285). • Systematic review and meta-analysis of NIBS techniques, including cTBS, rTMS, and tDCS, for treating GAD. • NIBS significantly reduces anxiety symptoms and improves response and remission rates. • The efficacy is notably contingent on the stimulation types employed. • Discerning headaches as an adverse event exhibited notable statistical disparities. [ABSTRACT FROM AUTHOR]

• Effects of transcranial static magnetic stimulation (tSMS) are state-dependent. • tSMS increases cortical excitability if applied on an inhibited M1. • Aftereffects of tSMS originate at synaptic level. Aftereffects of non-invasive brain stimulation techniques may be brain state-dependent. Either continuous theta-burst stimulation (cTBS) as transcranial static magnetic field stimulation (tSMS) reduce cortical excitability. Our objective was to explore the aftereffects of tSMS on a M1 previously stimulated with cTBS. The interaction effect of two inhibitory protocols on cortical excitability was tested on healthy volunteers (n = 20), in two different sessions. A first application cTBS was followed by real-tSMS in one session, or sham-tSMS in the other session. When intracortical inhibition was tested with paired-pulse transcranial magnetic stimulation, LICI (ie., long intracortical inhibition) increased, although the unconditioned motor-evoked potential (MEP) remained stable. These effects were observed in the whole sample of participants regardless of the type of static magnetic field stimulation (real or sham) applied after cTBS. Subsequently, we defined a group of good-responders to cTBS (n = 9) on whom the unconditioned MEP amplitude reduced after cTBS and found that application of real-tSMS (subsequent to cTBS) increased the unconditioned MEP. This MEP increase was not found when sham-tSMS followed cTBS. The interaction of tSMS with cTBS seems not to take place at inhibitory cortical interneurons tested by LICI, since LICI was not differently affected after real and sham tSMS. Our results indicate the existence of a process of homeostatic plasticity when tSMS is applied after cTBS. This work suggests that tSMS aftereffects arise at the synaptic level and supports further investigation into tSMS as a useful tool to restore pathological conditions with altered cortical excitability. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation is a noninvasive technique that can be used to evoke distributed network-level effects. Previous work demonstrated that the Hippocampal-Cortical Network responds preferably (i.e., greater memory improvement and increases in hippocampal-network connectivity) to continuous theta-burst stimulation protocol relative to intermittent theta-burst and to 20-Hz rTMS. Here, these data were further analyzed to characterize effects of continuous versus intermittent theta-burst stimulation on network-level connectivity measures -- as well as local connectedness -- via resting-state fMRI. In contrast to theories that propose continuous and intermittent theta-burst cause local inhibitory versus excitatory effects, respectively, both protocols caused local decreases in fMRI connectivity around the stimulated parietal site. While iTBS caused decreases in connectivity across the hippocampal-cortical network, cTBS caused increases and decreases in connectivity across the network. cTBS had no effect on the parietal-cortical network, whereas iTBS caused decreases in the right parietal cortex (contralateral hemisphere to the stimulation target). These findings suggest that continuous theta-burst may have entrained the endogenous hippocampal-cortical network, whereas the intermittent train was unable to maintain entrainment that may have yielded the long-lasting effects measured in this study (i.e., within 20-min post-stimulation). Furthermore, these effects were specific to the hippocampal-cortical network, which has a putative endogenous functionally-relevant theta rhythm, and not to the parietal network. These results add to the growing body of evidence that suggests effects of theta-burst stimulation are not fully characterized by excitatory/inhibitory theories. Further work is required to understand local and network-level effects of noninvasive stimulation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the treatment efficacy of neuromodulation versus sham for the treatment of tinnitus. Data Sources: Cochrane Library, CINAHL, PubMed, Scopus. Review Methods: The Cochrane Library, CINAHL, PubMed, and Scopus were searched from inception through May 2023 for English language articles documenting "neuromodulation" and "tinnitus" stratified by sham‐controlled randomized control trials with 40 or more patients. Data collected included Beck Anxiety Inventory, Beck Depression Inventory (BDI), Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire, and Visual Analog Scale. A Meta‐analysis of continuous measures (mean) and proportions (%) were conducted. Results: A total of 19 randomized control trials (N = 1186) were included. The mean age was 48.4 ± 5.3 (range: 19‐74), mean duration of tinnitus was 3.8 ± 3.4 years, 61% [56.2‐65.7] male, and 55.7% [46‐65] with unilateral tinnitus. The short‐term effect of transcutaneous electrical nerve stimulation and transcranial direct current stimulation on THI score is −16.2 [−23.1 to −9.3] and −19 [−30.1 to −7.8], respectively. The long‐term effect of repetitive transcranial magnetic stimulation on THI score is −8.6 [−11.5 to −5.7]. Transcranial direct current stimulation decreases BDI score by −11.8 [−13.3 to −10.3]. Conclusion: As measured by the Tinnitus Handicap Index, our findings suggest the effects of transcutaneous electrical nerve stimulation and transcranial direct current stimulation reach significant benefit in the short term, whereas repetitive transcranial magnetic stimulation reaches significant benefit in the long term. Based on the BDI, transcranial direct current stimulation significantly reduces comorbid depression in patients with tinnitus. [ABSTRACT FROM AUTHOR]

Non‐invasive brain stimulation has the potential to boost neuronal plasticity in the primary motor cortex (M1), but it remains unclear whether the stimulation of both superficial and deep layers of the human motor cortex can effectively promote M1 plasticity. Here, we leveraged transcranial ultrasound stimulation (TUS) to precisely target M1 circuits at depths of approximately 5 mm and 16 mm from the cortical surface. Initially, we generated computed tomography images from each participant's individual anatomical magnetic resonance images (MRI), which allowed for the generation of accurate acoustic simulations. This process ensured that personalized TUS was administered exactly to the targeted depths within M1 for each participant. Using long‐term depression and long‐term potentiation (LTD/LTP) theta‐burst stimulation paradigms, we examined whether TUS over distinct depths of M1 could induce LTD/LTP plasticity. Our findings indicated that continuous theta‐burst TUS‐induced LTD‐like plasticity with both superficial and deep M1 stimulation, persisting for at least 30 min. In comparison, sham TUS did not significantly alter M1 excitability. Moreover, intermittent theta‐burst TUS did not result in the induction of LTP‐ or LTD‐like plasticity with either superficial or deep M1 stimulation. These findings suggest that the induction of M1 plasticity can be achieved with ultrasound stimulation targeting distinct depths of M1, which is contingent on the characteristics of TUS. Key points: The study integrated personalized transcranial ultrasound stimulation (TUS) with electrophysiology to determine whether TUS targeting superficial and deep layers of the human motor cortex (M1) could elicit long‐term depression (LTD) or long‐term potentiation (LTP) plastic changes.Utilizing acoustic simulations derived from individualized pseudo‐computed tomography scans, we ensured the precision of TUS delivery to the intended M1 depths for each participant.Continuous theta‐burst TUS targeting both the superficial and deep layers of M1 resulted in the emergence of LTD‐like plasticity, lasting for at least 30 min.Administering intermittent theta‐burst TUS to both the superficial and deep layers of M1 did not lead to the induction of LTP‐ or LTD‐like plastic changes.We suggest that theta‐burst TUS targeting distinct depths of M1 can induce plasticity, but this effect is dependent on specific TUS parameters. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation is a noninvasive technique that can be used to evoke distributed network-level effects. Previous work demonstrated that the Hippocampal-Cortical Network responds preferably (i.e., greater memory improvement and increases in hippocampal-network connectivity) to continuous theta-burst stimulation protocol relative to intermittent theta-burst and to 20-Hz rTMS. Here, these data were further analyzed to characterize effects of continuous versus intermittent theta-burst stimulation on network-level connectivity measures – as well as local connectedness – via resting-state fMRI. In contrast to theories that propose continuous and intermittent theta-burst cause local inhibitory versus excitatory effects, respectively, both protocols caused local decreases in fMRI connectivity around the stimulated parietal site. While iTBS caused decreases in connectivity across the hippocampal-cortical network, cTBS caused increases and decreases in connectivity across the network. cTBS had no effect on the parietal-cortical network, whereas iTBS caused decreases in the right parietal cortex (contralateral hemisphere to the stimulation target). These findings suggest that continuous theta-burst may have entrained the endogenous hippocampal-cortical network, whereas the intermittent train was unable to maintain entrainment that may have yielded the long-lasting effects measured in this study (i.e., within 20-min post-stimulation). Furthermore, these effects were specific to the hippocampal-cortical network, which has a putative endogenous functionally-relevant theta rhythm, and not to the parietal network. These results add to the growing body of evidence that suggests effects of theta-burst stimulation are not fully characterized by excitatory/inhibitory theories. Further work is required to understand local and network-level effects of noninvasive stimulation.

BackgroundTinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone.Materials and methodsTen subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature.ResultsSubjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1-12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90-180 days).ConclusionsSequential rTMS approaches for the treatment of tinnitus-particularly those administering low-frequency treatment at left DLPFC-merit further investigation.

Background: Intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation can improve motor function in poststroke patients, but the therapeutic effect of this combination remains unclear. Objective: To determine the effects of central intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation on upper limb function. Methods: Fifty-six subacute stroke patients were randomly assigned to three groups: the CMS (n = 18), peripheral magnetic stimulation (PMS) (n = 19) and CPS (n = 19) groups. The CMS group received intermittent theta-burst stimulation and peripheral false stimulation, while the PMS group received repetitive peripheral magnetic stimulation and central false stimulation once a day for five days a week over four weeks. The CPS group received intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation simultaneously once daily for four weeks. The Fugl-Meyer Assessment, Action Research Arm Test, Modified Barthel Index and Modified Ashworth Scale evaluated outcomes before and after four weeks of treatment. Results: The motor function scores of all groups were significantly increased after treatment compared with before treatment, while the Modified Ashworth Scale score showed no significant change. There was a significant difference in the motor function score of the CPS group compared with that of the CMS and PMS groups, but there was no significant improvement in the Modified Ashworth Scale score. Conclusions: Combining the two treatment methods can improve patients' motor function and daily living abilities but cannot improve muscle tone. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation (TBS) is a repetitive transcranial magnetic stimulation technique that can be used to upregulate or downregulate different brain regions. However, the timing of its effects and the differing effects of continuous TBS (cTBS) versus intermittent TBS (iTBS) in the reading system have not been explored. This study assessed how stimulation type and post-stimulation timing affected change in performance during a phonological discrimination and sight word recognition task after stimulation of supramarginal gyrus (SMG). Fourteen right-handed young adults (age 18-27 years; 44% male) were block-randomized to receive either iTBS or cTBS to the supramarginal gyrus. Participants then performed a pseudoword discrimination task and an orthographic awareness task (behavioral control) at four different time points and change in reaction time compared to baseline was measured from each time point. There was no effect of stimulation type on change in reaction time [t(16) = -0.2, p = 0.9], suggesting that both types of TBS caused similar effects. Percent change in reaction time decreased over time in the pseudoword task [t(50) = -5.9, p < 0.001], indicating faster pseudoword processing speed with better performance 60-70 min after stimulation. In contrast, no change was demonstrated over time for the behavioral control task [t(43) = -0.6, p = 0.6], suggesting that the change over time seen in the test condition was not a learning effect. These findings provide insight into the effects of TBS on the reading system and can guide future study designs. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation (TBS) is a repetitive transcranial magnetic stimulation technique that can be used to upregulate or downregulate different brain regions. However, the timing of its effects and the differing effects of continuous TBS (cTBS) versus intermittent TBS (iTBS) in the reading system have not been explored. This study assessed how stimulation type and post-stimulation timing affected change in performance during a phonological discrimination and sight word recognition task after stimulation of supramarginal gyrus (SMG). Fourteen right-handed young adults (age 18–27 years; 44% male) were block-randomized to receive either iTBS or cTBS to the supramarginal gyrus. Participants then performed a pseudoword discrimination task and an orthographic awareness task (behavioral control) at four different time points and change in reaction time compared to baseline was measured from each time point. There was no effect of stimulation type on change in reaction time [t(16) = −0.2, p = 0.9], suggesting that both types of TBS caused similar effects. Percent change in reaction time decreased over time in the pseudoword task [t(50) = −5.9, p < 0.001], indicating faster pseudoword processing speed with better performance 60–70 min after stimulation. In contrast, no change was demonstrated over time for the behavioral control task [t(43) = −0.6, p = 0.6], suggesting that the change over time seen in the test condition was not a learning effect. These findings provide insight into the effects of TBS on the reading system and can guide future study designs.

Deep brain stimulation (DBS) is a widely used clinical therapy that modulates neuronal firing in subcortical structures, eliciting downstream network effects. Its effectiveness is determined by electrode geometry and location as well as adjustable stimulation parameters including pulse width, interstimulus interval, frequency, and amplitude. These parameters are often determined empirically during clinical or intraoperative programming and can be altered to an almost unlimited number of combinations. Conventional high-frequency stimulation uses a continuous high-frequency square-wave pulse (typically 130-160 Hz), but other stimulation patterns may prove efficacious, such as continuous or bursting theta-frequencies, variable frequencies, and coordinated reset stimulation. Here we summarize the current landscape and potential clinical applications for novel stimulation patterns. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response. Data was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis. The response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65–7.22). Less severe level of depression (Montgomery-Åsberg depression rating scale self-assessment < 36) at baseline predicted response and remission. Only <1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported. Retrospective analysis of register data. No comparison group. In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response. • iTBS is the most utilized rTMS protocol for depression in Sweden. • Real-life response rates of iTBS are similar to clinical trials. • Less severe depression is positively associated with response to iTBS. • Older age is positively associated with response to iTBS. [ABSTRACT FROM AUTHOR]

Aim: Bilateral theta‐burst stimulation (biTBS; intermittent TBS over the left dorsolateral prefrontal cortex [DLPFC] and continuous TBS over the right DLPFC) has demonstrated efficacy in improving symptoms in patients with major depressive disorder (MDD). However, the underlying brain mechanisms remain unknown. The authors aimed to investigate the antidepressant efficacy of biTBS monotherapy and its effects on the brain responses measured by functional magnetic resonance imaging (fMRI) during emotional processing in MDD. Methods: The authors conducted a double‐blind, randomized, sham‐controlled trial of patients with MDD who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode. Recruited patients were randomly assigned to 10 biTBS monotherapy or sham stimulation sessions. The fMRI scans during performing emotional recognition task were obtained at baseline and after 10 sessions of treatment. Depressive symptoms were assessed using the 21‐item Hamilton Rating Scale for Depression at baseline and the weeks 4, 8, 12, 16, 20, and 24 week. Results: The biTBS group (n = 17) exhibited significant decreases in depression scores compared with the sham group (n = 11) at week 8 (70% vs 40%; P = 0.02), and the significant differences persisted during the 24‐week follow‐up periods. At week 4, when the treatment course was completed, patients in the biTBS group, but not in the sham group, exhibited increased brain activities over the left superior and middle frontal gyrus during negative emotional stimuli. Conclusion: The authors' findings provide the first evidence regarding the underlying neural mechanisms of biTBS therapy to improve clinical symptoms in patients with MDD. [ABSTRACT FROM AUTHOR]

Visual hallucinations after central or peripheral impairment, commonly called Charles Bonnet syndrome, are often highly distressing and with few available treatment options. Here we report a case where an adolescent developed severely distressing visual hallucinations after hypoxic damage to the occipital cortex following a suicide attempt. The patient received active and sham occipital continuous theta-burst stimulation (cTBS) in a single-case experimental research design and a subsequent open phase, to evaluate cTBS as a Charles Bonnet treatment. The visual hallucinations seemed to decrease more during active than sham cTBS in the blind phase, and in the following week of repeated five daily treatments they almost disappeared. A normalization of increased activity in the lateral visual network after cTBS was observed on a functional magnetic resonance imaging resting-state analysis compared with 42 healthy controls. Visual evoked potentials stayed largely unchanged both in the sham-controlled blind phase and the subsequent open phase. During the two weeks after the open phase with repeated cTBS sessions, the visual hallucinations gradually reappeared and almost returned to the baseline level. Our findings suggest that active cTBS over the primary visual cortex can reduce visual hallucinations through modulation of downstream visual regions, though the effect is temporally limited. [ABSTRACT FROM AUTHOR]

Background: Theta-burst transcranial magnetic stimulation has demonstrated promising effectiveness as treatment for post-traumatic stress disorder (PTSD) and depression. However, the effect of accelerated theta-burst stimulation (TBS) in comorbid with PTSD and depression remains unknown. Case presentation: We report a case of a 25-year-old woman with PTSD and depression whose symptoms markedly improved after continuous TBS of the right dorsolateral prefrontal cortex (DLPFC) and intermittent TBS (iTBS) over the left DLPFC, and then with 20min break before the 2nd iTBS session. Conclusions: Accelerated TBS over the bilateral DLPFCmay improve severe PTSD and depression. Accelerated TBS may have more improvement of depression symptoms than PTSD symptoms. Further trials are warranted to investigate the effect and safety for patients with complicated PTSD and depression. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is a widely used clinical therapy that modulates neuronal firing in subcortical structures, eliciting downstream network effects. Its effectiveness is determined by electrode geometry and location as well as adjustable stimulation parameters including pulse width, interstimulus interval, frequency, and amplitude. These parameters are often determined empirically during clinical or intraoperative programming and can be altered to an almost unlimited number of combinations. Conventional high-frequency stimulation uses a continuous high-frequency square-wave pulse (typically 130–160 Hz), but other stimulation patterns may prove efficacious, such as continuous or bursting theta-frequencies, variable frequencies, and coordinated reset stimulation. Here we summarize the current landscape and potential clinical applications for novel stimulation patterns.

In chronic stroke, transcranial magnetic stimulation is used to investigate if the primary motor cortex (M1) of the unlesioned hemisphere (UH) optimizes or hampers the functional gains. Continuous and intermittent theta-burst stimulation (cTBS, iTBS) were used to decrease and increase UH-M1 excitability, respectively. However, the effects of these protocols were never compared in the same patients and studies remain controversial. Therefore, the present study first compared the two protocols in the same patient, a 60-yo male at a chronic stage post-stroke, then tested in the long-term the protocol with the largest after-effects. To this end, experiment 1 compared the after-effects of iTBS, cTBS, and sham over UH-M1 (one session each, one week apart): data showed that the paretic hand motricity and M1 excitability of the lesioned hemisphere (LH) were improved after cTBS only. cTBS was then administrated over 10 sessions in experiment 2 and the outcomes were tested at different timepoints: M1 excitability was improved in both hemispheres and the functional gains obtained during cTBS sessions were still present three months after the end of stimulation. In conclusion, our chronic case study showed that UH inhibition, and not activation, promoted the function in a patient with spared corticospinal control from LH. Group studies in chronic stroke should reproduce our experiments and determine if, to optimize the gains, UH should be inhibited in patients with spared LH function (our case) or activated in patients with lost LH function, as already hypothesized. This is of major interest in neurorehabilitation using TMS protocols.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. While the symptoms of ASD are present from early childhood, there has been an increase in the number of adults with ASD in recent years who visit healthcare professionals to seek the treatment of depression due to maladjustment resulting from the core symptoms and are eventually diagnosed with ASD. Currently, no treatment is available for the core symptoms of ASD, and pharmacotherapy and psychotherapy are often provided mainly for secondary disorders such as depression and anxiety. However, the effectiveness of these therapies is often limited in individuals with ASD compared to those with major depression. In this context, neuromodulation therapies such as transcranial magnetic stimulation (TMS) have gained increasing attention as potential treatments. In this case series, we retrospectively analyzed 18 cases with ASD from the TMS registry data who had failed to improve depressive symptoms with pharmacotherapy and were treated with intermittent theta burst stimulation (iTBS) therapy to the left dorsolateral prefrontal cortex (DLPFC). We also explored the relationship between treatment efficacy and clinical epidemiological profile. Our results indicated that, despite the limitations of an open-label preliminary case series, TMS therapy in the form of iTBS may have some beneficial therapeutic effects on depressive symptoms in individuals with ASD. The present findings warrant further validation through randomized, sham-controlled trials with larger sample sizes. [ABSTRACT FROM AUTHOR]

Gambling Disorder (GD) is a condition constituting a public health concern, with a burden of harm which is much greater than that of drug addiction. Patients with GD are generally reluctant to pharmacologic treatment and seem to prefer nonpharmacological interventions. Therefore, this proof-of-concept study aimed to investigate the feasibility of continuous Theta Burst Stimulation (cTBS) on the pre-SMA in six patients (5 males, 1 female), aged 30–64 years, with a DSM-5 diagnosis of Gambling Disorder and no comorbid mood disorders. Participants received over 10 sessions of Continuous TBS (cTBS) over pre-SMA bilaterally and have been evaluated using rating scales, including the PG-YBOCS and the CGI, before treatment (T0), at day 10 of treatment (T1) and at day 30 after treatment (T2); cTBS intervention was safe and without side effects. Since the design of our study does not allow us to draw conclusions on the effectiveness of the intervention with respect to the improvement of the functioning of the subject with GD, a more in-depth study, including a sham condition, neurocognitive measures of disinhibition and decision making, and collecting follow-up data on the sustained effect of TBS over a longer period is ongoing. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the effect of intermittent theta-burst stimulation (iTBS) on visual working memory for people suffering from methamphetamine use disorder (MUD). Five sessions of iTBS were carried over the left dorsolateral prefrontal cortex (DLPFC) or the vertex as a sham control, with each session in one day. Orientation free-recall tasks were conducted before the iTBS stimulation, after the first and fifth sessions of stimulation. Results showed that when compared with the sham group, a single session of iTBS over the left DLPFC improved participants' working memory performance. Specifically, iTBS over the left DLPFC increased the working memory capacity and such effects enlarged with multiple sessions. The present finding suggested that iTBS over DLPFC could be a promising intervention method to enhance the cognitive function of addicts with MUD. [ABSTRACT FROM AUTHOR]

• Further evidence of hyperplasticity in the brain of individuals with autism. • 'Mechanism-driven' rTMS that potentiates brain inhibitory mechanisms could stabilize cortical hyperplasticity in autism. • 'Mechanism-driven' rTMS innovations hold promise for developing plasticity-based novel interventions for autism. Emerging evidence implicates atypical plasticity in the neurophysiology of autism spectrum disorder (ASD). Specifically, autistic people demonstrated hyperplasticity in response to theta-burst stimulation (TBS). We hypothesized that autistic adults would display hyperplasticity to TBS and that repetitive transcranial magnetic stimulation (rTMS) – which potentiates brain inhibitory mechanisms – would 'stabilize' hyperplasticity. Using a randomized, cross-over design, plasticity was assessed using TBS in the left motor cortex (M1) in 31 autistic adults and 30 sex-, intelligence quotient-, and age-matched controls. Autistic adults (n = 29) were further randomized (1:1) to receive a single session of active (n = 14) or sham (n = 15) rTMS (6000 pulses at 20 Hz) over left M1 and plasticity was reassessed on the next day following rTMS. Both long-term potentiation (LTP) and long-term depression (LTD) were significantly increased in the ASD group, indicating hyperplasticity. Active, but not sham rTMS, attenuated LTD in autistic adults. We provided further evidence for the presence of brain hyperplasticity in ASD. To our knowledge, this is the first study to show preliminary evidence that an excessive LTD in ASD can be 'stabilized' using rTMS. Such 'stabilizing' effect of rTMS on LTP was not observed, likely due to small sample size or a more specific 'attenuating' effect of rTMS on LTD, compared to LTP. These findings indicate atypical brain inhibitory mechanisms behind hyperplasticity in ASD. Utilizing a larger sample, future replication studies could investigate therapeutic opportunities of 'mechanism-driven' rTMS. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation is a non-invasive brain stimulation technique that was introduced as a potential augmentation treatment for patients with schizophrenia. The purpose of this meta-analysis was to investigate the therapeutic efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia. Following the PRISMA guidelines, the MEDLINE, Embase, Cochrane, Scopus, Web of Science, and CNKI databases were searched for relevant studies from database inception to 9 January 2022. Change in symptom severity among patients with schizophrenia was the primary outcome, and changes in cognitive function and safety profiles, including the discontinuation rate and adverse events, were secondary outcomes. In total, 13 double-blind randomized sham-controlled trials with 524 patients were included. Intermittent theta-burst stimulation adjunct to antipsychotics was associated with significantly improved psychopathology in patients with schizophrenia, particularly for negative symptoms and general psychopathology but not for positive symptoms or cognitive function. The stimulation parameters influenced the effectiveness of intermittent theta-burst stimulation. A more favorable effect was observed in patients who received thetaburst stimulation at the left dorsolateral prefrontal cortex, with ≥1800 pulses per day, for ≥20 sessions, and using an inactive sham coil as a placebo comparison in the study. The intermittent theta-burst stimulation is well tolerated and safe in patients with schizophrenia. Intermittent theta-burst stimulation adjunct to antipsychotics treatment is associated with significant improvement in negative symptoms and favorable tolerability in patients with schizophrenia. This metaanalysis may provide insights into the use of intermittent theta-burst stimulation as an additional treatment to alleviate the negative symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

Vascular cognitive impairment and dementia (VCID) is mainly caused by chronic cerebral hypoperfusion and subsequent white matter lesions. Noninvasive transcranial magnetic stimulation has been utilized in treating various neurological disorders. However, the function of theta-burst transcranial magnetic stimulation on VCID remains to be defined. We utilized 4-week bilateral carotid artery stenosis model of male mice to mimic VCID. Intermittent theta-burst stimulation (iTBS) or consecutive theta-burst stimulation (cTBS) was administered for 14 consecutive days. Through luxol fast blue staining, electron microscopy and immunofluorescence, we found that iTBS, not cTBS, significantly improved demyelination, axonal damage and β-amyloid deposition, without affecting cerebral blood flow in VCID mice. At cellular levels, iTBS rescued the loss of mature oligodendrocytes, promoted precursor cell differentiation, and inhibited pro-inflammatory activation of astrocytes and microglia. Notably, iTBS attenuated cognitive deterioration in both short-term retention and long-term spatial memory of VCID mice as indicated by serial neurobehavioral tests. To explore the molecular involvement of iTBS, mRNA sequencing was carried out. By real-time PCR and combined RNA fluorescence in situ hybridization with immunofluorescence, iTBS was confirmed to increase Rxrg expression specifically in mature oligodendrocytes. Collectively, iTBS could ameliorate vascular cognitive dysfunction, probably via mitigating white matter lesions and neuroinflammation in the corpus callosum. Rxrg signaling in mature oligodendrocytes, which was increased by iTBS, might be a potential target for VCID treatment., (Copyright © 2024. Published by Elsevier Inc.)

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder, with 30–40% of OCD patients being unresponsive to adequate trials of anti-OCD drugs and cognitive behavior therapy. The aim of this paper is to investigate the efficacy of non-invasive brain stimulation (NIBS) on treating refractory OCD. With PubMed, Embase, PsycInfo, and Cochrane Library used on 15 February 2022, 24 randomized controlled trials involving 663 patients were included. According to this analysis, NIBS including repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcranial direct current stimulation (tDCS), had a moderate effect on the reduction of Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (SMD = 0.54, 95% CI: 0.26–0.81; p < 0.01). In the subgroup analysis, rTMS seemed to produce a better therapeutic effect (SMD = 0.73, 95% CI: 0.38–1.08; p < 0.01). Moreover, excitatory (SMD = 1.13, 95% CI: 0.24–2.01; p = 0.01) and inhibitory (SMD = 0.81, 95% CI: 0.26–1.36; p < 0.01) stimulation of the dorsolateral prefrontal cortex (DLPFC) both alleviated OCD symptoms. In the secondary outcome of clinical response rates, NIBS treatment led to an increase in response rates (RR = 2.26, 95% CI: 1.57–3.25; p < 0.01). [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic potential for treating patients with methamphetamine use disorder (MUD). However, the most effective target and stimulation frequency of rTMS for treating MUD remains unclear. This meta-analysis explored the effect of rTMS on MUD. Methods: In this study, PubMed, Cochrane Systematic Reviews, and the Cochrane Collaboration Central Register of Controlled Clinical Trials were searched electronically for double-blind randomized controlled trials that used rTMS for treating MUD. We used published trials to investigate the efficacy of rTMS in MUD up to March 5, 2022, and pooled studies using a random-effect model to compare rTMS treatment effects. Patients who were diagnosed with MUD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders were recruited. Clinical craving scores between baseline and after rTMS were compared using the standardized mean difference (SMD) with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through a visual inspection of funnel plots and the I2 statistic. Results: We identified seven trials with 462 participants with MUD that met the inclusion criteria. All the studies evaluated craving scores, with rTMS demonstrating a more significant effect than the sham treatment on reducing craving scores (SMD = 0.983, CI = 0.620–1.345, p ≤ 0.001). A subgroup meta-analysis revealed that intermittent theta-burst stimulation (iTBS) had a greater positive effect than 10-Hz rTMS. A metaregression revealed that the SMDs increased with the increase in baseline craving scores, whereas they decreased with the increase in the proportion of men and duration of abstinence. Conclusion: The meta-analysis suggests that rTMS may be associated with treatment effect on craving symptoms in patients with MUD. iTBS may have a greater positive effect on craving reduction than 10-z rTMS. [ABSTRACT FROM AUTHOR]

Background: Tinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone. Materials and Methods: Ten subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature. Results: Subjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1–12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90–180 days). Conclusions: Sequential rTMS approaches for the treatment of tinnitus—particularly those administering low-frequency treatment at left DLPFC—merit further investigation. [ABSTRACT FROM AUTHOR]

BackgroundTinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone.Materials and MethodsTen subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature.ResultsSubjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1–12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90–180 days).ConclusionsSequential rTMS approaches for the treatment of tinnitus—particularly those administering low-frequency treatment at left DLPFC—merit further investigation.

Objective: High-frequency repetitive transcranial magnetic stimulation (rTMS) induces analgesic effects in both experimental pain and clinical pain conditions. However, whether rTMS can modulate sensory and pain thresholds on sensory fibers is still unclear. Here, we compared the effects of three rTMS paradigms on sensory and pain thresholds conducted by different sensory fibers (Aβ, Aδ, and C fibers) with sham stimulation and investigate the potential brain activation using functional near-infrared spectroscopy (fNIRS). Methods: Forty right-handed healthy subjects were randomly allocated into one of four groups. Each subject received one session rTMS [prolonged continuous theta-burst stimulation (pcTBS), intermittent theta-burst stimulation (iTBS), 10 Hz rTMS or sham]. Current perception threshold (CPT), pain tolerance threshold (PTT), and fNIRS were measured at baseline, immediately after stimulation, and 1 h after stimulation, respectively. Results: Significant differences between treatments were observed for changes for CPT 2,000 Hz between baseline and 1 h after rTMS (F = 6.551, P < 0.001): pcTBS versus sham (P = 0.004) and pcTBS versus 10 Hz rTMS (P = 0.007). There were significant difference in average HbO μm in the right frontopolar cortex (FPC) [channel 23: P = 0.030 (pcTBS versus sham: P = 0.036)], left dorsolateral prefrontal cortex (DLPFC) [channel 7: P = 0.006 (pcTBS versus sham: P = 0.004)], left FPC [channel 17: P = 0.014 (pcTBS versus sham: P = 0.046), channel 22: P = 0.004 (pcTBS versus sham: P = 0.004)] comparing four group in 1 h after stimulation in PTT 2000 Hz (Aβ-fiber). Conclusion: Prolonged continuous theta-burst stimulation can regulate sensitivity on Aβ fibers. In addition, single-session pcTBS placed on left M1 can increase the excitability of DLPFC and FPC, indicating the interaction between M1 and prefrontal cortex may be a potential mechanism of analgesic effect of rTMS. Studies in patients with central post-stroke pain are required to confirm the potential clinical applications of pcTBS. [ABSTRACT FROM AUTHOR]

ObjectiveHigh-frequency repetitive transcranial magnetic stimulation (rTMS) induces analgesic effects in both experimental pain and clinical pain conditions. However, whether rTMS can modulate sensory and pain thresholds on sensory fibers is still unclear. Here, we compared the effects of three rTMS paradigms on sensory and pain thresholds conducted by different sensory fibers (Aβ, Aδ, and C fibers) with sham stimulation and investigate the potential brain activation using functional near-infrared spectroscopy (fNIRS).MethodsForty right-handed healthy subjects were randomly allocated into one of four groups. Each subject received one session rTMS [prolonged continuous theta-burst stimulation (pcTBS), intermittent theta-burst stimulation (iTBS), 10 Hz rTMS or sham]. Current perception threshold (CPT), pain tolerance threshold (PTT), and fNIRS were measured at baseline, immediately after stimulation, and 1 h after stimulation, respectively.ResultsSignificant differences between treatments were observed for changes for CPT 2,000 Hz between baseline and 1 h after rTMS (F = 6.551, P < 0.001): pcTBS versus sham (P = 0.004) and pcTBS versus 10 Hz rTMS (P = 0.007). There were significant difference in average HbO μm in the right frontopolar cortex (FPC) [channel 23: P = 0.030 (pcTBS versus sham: P = 0.036)], left dorsolateral prefrontal cortex (DLPFC) [channel 7: P = 0.006 (pcTBS versus sham: P = 0.004)], left FPC [channel 17: P = 0.014 (pcTBS versus sham: P = 0.046), channel 22: P = 0.004 (pcTBS versus sham: P = 0.004)] comparing four group in 1 h after stimulation in PTT 2000 Hz (Aβ-fiber).ConclusionProlonged continuous theta-burst stimulation can regulate sensitivity on Aβ fibers. In addition, single-session pcTBS placed on left M1 can increase the excitability of DLPFC and FPC, indicating the interaction between M1 and prefrontal cortex may be a potential mechanism of analgesic effect of rTMS. Studies in patients with central post-stroke pain are required to confirm the potential clinical applications of pcTBS.

Designer receptors exclusively activated by designer drug (DREADDs) are a novel tool with the potential to bidirectionally drive cellular, circuit, and ultimately, behavioral changes. We used DREADDs to evaluate memory formation in a hippocampus-dependent task in mice and effects on synaptic physiology in the dorsal hippocampus. We expressed neuron-specific (hSyn promoter) DREADDs that were either excitatory (HM3D) or inhibitory (HM4D) in the dorsal hippocampus. As predicted, hSyn-HM3D was able to transform a subthreshold learning event into long-term memory (LTM), and hSyn-HM4D completely impaired LTM formation. Surprisingly, the opposite was observed during experiments examining the effects on hippocampal long-term potentiation (LTP). hSyn-HM3D impaired LTP and hSyn-HM4D facilitated LTP. Follow-up experiments indicated that the hSyn-HM3D-mediated depression of fEPSP appears to be driven by presynaptic activation of inhibitory currents, whereas the hSyn-HM4D-mediated increase of fEPSP is induced by a reduction in GABAA receptor function. To determine whether these observations were promoter specific, we next examined the effects of using the CaMKIIα promoter that limits expression to forebrain excitatory neurons. CaMKIIα-HM3D in the dorsal hippocampus led to the transformation of a subthreshold learning event into LTM, whereas CaMKIIα-HM4D blocked LTM formation. Consistent with these findings, baseline synaptic transmission and LTP was increased in CaMKIIα-HM3D hippocampal slices, whereas slices from CaMKIIα-HM4D mice produced expected decreases in baseline synaptic transmission and LTP. Together, these experiments further demonstrate DREADDs as being a robust and reliable means of modulating neuronal function to manipulate long-term changes in behavior, while providing evidence for specific dissociations between LTM and LTP.Significance statementThis study evaluates the efficacy of designer receptors exclusively activated by designer drug (DREADDs) as a means of bidirectionally modulating the hippocampus in not only a hippocampus-dependent task but also in hippocampal synaptic plasticity. This is the first study to evaluate the effects of DREADD-mediated inhibition and excitation in hippocampal long-term potentiation. More specifically, this study evaluates the effect of promoter-specific expression of DREADD viruses in a heterogenic cell population, which revealed surprising effects of different promoters. With chemogenetics becoming a more ubiquitous tool throughout studies investigating circuit-specific function, these data are of broad interest to the neuroscientific community because we have shown that promoter-specific effects can drastically alter synaptic function within a specific region, without parallel changes at the level of behavior.

Background: Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. Objective/Hypothesis: This study brought together over 60 TMS researchers to form the ‘Big TMS Data Collaboration’, and create the largest known sample of individual participant TBS data to date. The goal was to enable a more comprehensive evaluation of factors driving TBS response variability. Methods: 118 corresponding authors of TMS studies were emailed and asked to provide deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to iTBS and cTBS response variability. Results: 430 healthy participants’ TBS data was pooled across 22 studies (mean age = 41.9; range = 17–82; females = 217). Baseline MEP amplitude, age, target muscle, and time of day significantly predicted iTBS-induced plasticity. Baseline MEP amplitude and timepoint after TBS significantly predicted cTBS-induced plasticity. Conclusions: This is the largest known study of interindividual variability in TBS. Our findings indicate that a significant portion of variability can be attributed to the methods used to measure the modulatory effects of TBS. We provide specific methodological recommendations in order to control and mitigate these sources of variability.

Background: Chronic orofacial pain (COP) patients often perceive the painful face area as “swollen” without clinical signs; such self-reported illusions of the face are termed perceptual distortion (PD). The pathophysiological mechanisms underlying PD remain elusive. Objective: To test the neuromodulatory effect of repetitive transcranial magnetic stimulation (rTMS) on PD in healthy individuals, to gain insight into the cortical mechanisms underlying PD. Methods: PD was induced experimentally by injections of local anesthetic (LA) around the infraorbital nerve and measured as perceived size changes of the affected area. Participants were randomly allocated to inhibitory rTMS (n = 26) or sham rTMS (n = 26) group. The participants rated PD at baseline, 6 min after LA, immediately, 20 and 40 min after rTMS. The rTMS (inhibitory and sham) was applied to face (lip) representation area of primary somatosensory cortex (SI) as an intervention at 10 min after the LA, when the magnitude of PD is large. As inhibitory rTMS, continuous theta-burst stimulation paradigm (50 Hz) for 40s was employed to inhibit cortical activity. Results: We demonstrated a significant decrease in the magnitude of PD immediately and 20 min after the application of inhibitory rTMS compared with sham rTMS (P

Adjacent regions of parietal cortex are thought to affiliate with distinct large-scale networks and thereby make different contributions to memory formation. We directly tested this putative functional segregation within parietal cortex by perturbing activity of anterior versus posterior parietal areas. We applied noninvasive theta-burst transcranial magnetic stimulation to these locations immediately before a semantic encoding task, and subsequently tested recollection memory. Consistent with previous findings, fMRI activity in left inferior frontal gyrus during semantic encoding correlated with subsequent high memory accuracy and strong subjective recollection. Stimulation of the posterior parietal cortex decoupled its network – the hippocampal-cortical network – from left inferior frontal gyrus. Furthermore, posterior parietal stimulation reduced highly accurate subjective recollection. Critically, both of these changes occurred relative to stimulation of the anterior parietal cortex. Stimulating anterior versus posterior parietal cortex therefore differentiated hippocampal network involvement in episodic memory. This provides direct evidence that distinct territories within close proximity of each other in parietal cortex make functionally distinct contributions to memory formation. Further, noninvasive stimulation has the spatial resolution required to differentially modulate the interaction of these adjacent parietal locations with distributed large-scale brain networks.

Background: Repetitive transcranial magnetic stimulation (rTMS) induces long-term changes of synapses, but the mechanisms behind these modifications are not fully understood. Although there has been progress in the development of multi-scale modeling tools, no comprehensive module for simulating rTMS-induced synaptic plasticity in biophysically realistic neurons exists.., Objective: We developed a modelling framework that allows the replication and detailed prediction of long-term changes of excitatory synapses in neurons stimulated by rTMS., Methods: We implemented a voltage-dependent plasticity model that has been previously established for simulating frequency-, time-, and compartment-dependent spatio-temporal changes of excitatory synapses in neuronal dendrites. The plasticity model can be incorporated into biophysical neuronal models and coupled to electrical field simulations., Results: We show that the plasticity modelling framework replicates long-term potentiation (LTP)-like plasticity in hippocampal CA1 pyramidal cells evoked by 10-Hz repetitive magnetic stimulation (rMS). This plasticity was strongly distance dependent and concentrated at the proximal synapses of the neuron. We predicted a decrease in the plasticity amplitude for 5 Hz and 1 Hz protocols with decreasing frequency. Finally, we successfully modelled plasticity in distal synapses upon local electrical theta-burst stimulation (TBS) and predicted proximal and distal plasticity for rMS TBS. Notably, the rMS TBS-evoked synaptic plasticity exhibited robust facilitation by dendritic spikes and low sensitivity to inhibitory suppression., Conclusion: The plasticity modelling framework enables precise simulations of LTP-like cellular effects with high spatio-temporal resolution, enhancing the efficiency of parameter screening and the development of plasticity-inducing rTMS protocols., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Unilateral neglect (UN) is a common and disabling disorder after stroke. UN is a strong and negative predictor of functional rehabilitative outcome. Non-invasive brain stimulation, such as theta-burst transcranial magnetic stimulation (TBS), is a promising rehabilitation technique for treating stroke-induced UN. Objective: To systematically review the available literature, researching whether TBS of the contra-lesional hemisphere is more effective than standard rehabilitation in improving symptoms of UN in patients with right hemisphere stroke. Review methods: A systematic review was conducted to retrieve randomized controlled trials (RCTs) that were relevant to the objective of this review. PubMed, Ovid and Cochrane Library electronic databases were comprehensively searched from inception up to February 2021. Of the included studies, methodological quality was assessed using the PEDro scale, whereafter a best evidence synthesis (BES) was conducted to summarize the results. Results: Nine RCTs investigating the effects of TBS on stroke-induced UN symptoms were included in this review. Seven studies assessing continuous TBS (cTBS) found significantly greater amelioration of UN symptoms in the TBS intervention group when compared to the control group; one study assessing cTBS found no such significant difference. One study assessing intermittent TBS (iTBS) found significant between-group differences in favor of the intervention. The BES yielded strong evidence in favor of cTBS, and limited evidence in favor of iTBS. Conclusions: The included studies in the present review allow the conclusion that TBS can have favorable effects on UN recovery in stroke patients. Its clinical use is recommended in conjunction with cognitive rehabilitation and occupational or physical rehabilitation as needed. However, many aspects for optimal usage of TBS therapy in clinical settings, such as exact TBS protocols, number of sessions, and treatment duration, are not clear. [ABSTRACT FROM AUTHOR]

• Tonic cerebellar input to motor cortex (M1) modulates its plastic response. • Increasing cerebellar input to M1 converts Non-Responder to paired associative stimulation (PAS) to Responder. • Decreasing cerebellar input to M1 converts PAS effect to LTD-like effect. The extent of plastic responses of motor cortex (M1) to paired associative stimulation (PAS) varies among healthy subjects. Continuous theta-burst stimulation (cTBS) of cerebellum enhances the mean PAS-induced plasticity in groups of healthy subjects. We tested whether the initial status of Responder or Non -Responder to PAS, influenced the effect of cerebellar stimulation on PAS-induced plasticity. We assessed in 19 young healthy volunteers (8 Responders, 11 Non-Responders to PAS), how cTBS and iTBS (intermittent TBS) applied to the cerebellum before a PAS protocol influenced the plastic responsiveness of M1 to PAS. We tested whether the PAS-induced plastic effects could be depotentiated by a short cTBS protocol applied to M1 shortly after PAS and whether cerebellar stimulation influenced GABA-ergic intracortical inhibition and M1 plasticity in parallel. Cerebellar cTBS restored the M1 response to PAS in Non-Responders while cerebellar iTBS turned the potentiating response to PAS to a depressive response in both groups. The depotentiation protocol abolished both responses. Non-Responder status to PAS is a state of M1 amenable to bidirectional plastic modulation when primed by a change in cerebello-thalamic drive. The meaning of lack of responsiveness to certain protocols probing plasticity should be reconsidered. [ABSTRACT FROM AUTHOR]

While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof-of-concept study employed a multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and the basal ganglia during motor learning. Our results indicate that while stimulation did not modulate motor performance nor task-related brain activity, it influenced connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence, to the best of our knowledge, that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.

The present study aimed to explore the effect of intermittent theta-burst stimulation (iTBS) on visual working memory for people suffering from methamphetamine use disorder (MUD). Five sessions of iTBS were carried over the left dorsolateral prefrontal cortex (DLPFC) or the vertex as a sham control, with each session in one day. Orientation free-recall tasks were conducted before the iTBS stimulation, after the first and fifth sessions of stimulation. Results showed that when compared with the sham group, a single session of iTBS over the left DLPFC improved participants’ working memory performance. Specifically, iTBS over the left DLPFC increased the working memory capacity and such effects enlarged with multiple sessions. The present finding suggested that iTBS over DLPFC could be a promising intervention method to enhance the cognitive function of addicts with MUD.

Introduction: Theta-burst stimulation (TBS) is a safe non-invasive neurostimulation technique used to improve cognitive and neuropsychiatric impairments. Combined outcome evaluation using event-related potentials (ERPs) and neuropsychological tests may allow a more thorough assessment of TBS treatment efficacy; however, some mixed results have been found, and their use remains scarce. Our main objective was to evaluate whether a session of TBS to the left dorsolateral prefrontal cortex (DLPFC) can impact upon the performance of both neuropsychological and neurophysiological tests. Methods: This double-blind sham-controlled study involved 28 healthy adults, between 18 and 30 years. Volunteers were randomly allocated to receive excitatory (intermittent [iTBS]), inhibitory (continuous TBS [cTBS]) or sham stimulation on the left DLPFC. Subjects were evaluated using ERPs (auditory oddball paradigm P300) and neuropsychological tests (Trail making test [TMT] and Stroop test of words and colours [STWC]), using a pre-post stimulation protocol. Results: Inhibitory stimulation led to significantly delayed P300 peak latencies (p < 0.001), with no consistent change in N2P3 amplitudes. cTBS also significantly influenced the expected group performance in Stroop C and Stroop interference (p = 0.025) compared to the iTBS and sham groups. No significant results were found in TMT tests after TBS. Conclusion: Our results suggest that P300 and specific Stroop colour and words test parameters can be similarly influenced by the same TBS protocol. This emphasizes the importance of mixed evaluation using neuropsychological and neurophysiological resources in research associated with the use of transcranial magnetic stimulation and cognition. [ABSTRACT FROM AUTHOR]

• Gamma-transcranial alternating current stimulation (γ-tACS) boosted the iTBS-induced plasticity in both young and older adults. • The effects of iTBS-γ tACS as well as of γ-tACS alone were significantly weaker in older than young adults. • The effects of iTBS-γ tACS negatively correlated with the age of older adults. In healthy subjects, the long-term potentiation (LTP)-like plasticity of the primary motor cortex (M1) induced by intermittent theta-burst stimulation (iTBS) can be boosted by modulating gamma (γ) oscillations through transcranial alternating current stimulation (tACS). γ-tACS also reduces short-interval intracortical inhibition (SICI). We tested whether the effects of γ-tACS differ between young (YA) and older adults (OA). Twenty YA (27.2 ± 2.7 years) and twenty OA (65.3 ± 9.5 years) underwent iTBS-γ tACS and iTBS-sham tACS in randomized sessions. In a separate session, we delivered γ-tACS alone and recorded SICI during stimulation. iTBS-sham tACS produced comparable motor evoked potential (MEP) facilitation between groups. While iTBS-γ tACS boosted MEP facilitation in both the YA and OA groups, the magnitude of its effect was significantly lower in OA. Similarly, γ-tACS-induced modulation of GABA-A-ergic neurotransmission, as tested by SICI, was reduced in OA. The effect of iTBS-γ tACS negatively correlated with the age of OA subjects. Mechanisms underlying the effects of γ oscillations on LTP-like plasticity become less efficient in older adults. This could reflect age-related changes in neural elements of M1 resonant to γ oscillations, including GABA-A-ergic interneurons. The beneficial effect of γ-tACS on iTBS-induced plasticity is reduced in older adults. [ABSTRACT FROM AUTHOR]

• Bilateral theta-burst stimulation results in reduced depressive symptoms. • No effect is present on executive functions after the stimulation. • Psychomotor speed can potentially be increased by theta-burst stimulation. Major depressive disorder (MDD) is characterized by severe affective as well as cognitive symptoms. Moreover, cognitive impairment in MDD can persist after the remission of affective symptoms. Theta-burst stimulation (TBS) is a promising tool to manage the affective symptoms of major depressive disorder (MDD); however, its cognition-enhancing effects are sparsely investigated. Here, we aimed to examine whether the administration of bilateral TBS has pro-cognitive effects in MDD. Ten daily sessions of neuronavigated active or sham TBS were delivered bilaterally over the dorsolateral prefrontal cortex to patients with MDD. The n-back task and the attention network task were administered to assess working memory and attention, respectively. Affective symptoms were measured using the 21-item Hamilton Depression Rating Scale. We observed moderate evidence that the depressive symptoms of patients receiving active TBS improved compared to participants in the sham stimulation. No effects of TBS on attention and working memory were detected, supported by a moderate-to-strong level of evidence. The effects of TBS on psychomotor processing speed should be further investigated. Bilateral TBS has a substantial antidepressive effect with no immediate adverse effects on executive functions. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are evidenced-based treatments for patients with major depressive disorder (MDD) who fail to respond to standard first-line therapies. However, although various TMS protocols have been proven to be clinically effective, the response rate varies across clinical applications due to the heterogeneity of real-world psychiatric comorbidities, such as generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or substance use disorder, which are often observed in patients with MDD. Therefore, individualized treatment approaches are important to increase treatment response by assigning a given patient to the most optimal TMS treatment protocol based on his or her individual profile. This literature review summarizes different rTMS or TBS protocols that have been applied in researches investigating MDD patients with certain psychiatric comorbidities and discusses biomarkers that may be used to predict rTMS treatment response. Furthermore, we highlight the need for the validation of neuroimaging and electrophysiological biomarkers associated with rTMS treatment responses. Finally, we discuss on which directions future efforts should focus for developing the personalization of the treatment of depression with rTMS or iTBS. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder, with 30–40% of OCD patients being unresponsive to adequate trials of anti-OCD drugs and cognitive behavior therapy. The aim of this paper is to investigate the efficacy of non-invasive brain stimulation (NIBS) on treating refractory OCD. With PubMed, Embase, PsycInfo, and Cochrane Library used on 15 February 2022, 24 randomized controlled trials involving 663 patients were included. According to this analysis, NIBS including repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcranial direct current stimulation (tDCS), had a moderate effect on the reduction of Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (SMD = 0.54, 95% CI: 0.26–0.81; p < 0.01). In the subgroup analysis, rTMS seemed to produce a better therapeutic effect (SMD = 0.73, 95% CI: 0.38–1.08; p < 0.01). Moreover, excitatory (SMD = 1.13, 95% CI: 0.24–2.01; p = 0.01) and inhibitory (SMD = 0.81, 95% CI: 0.26–1.36; p < 0.01) stimulation of the dorsolateral prefrontal cortex (DLPFC) both alleviated OCD symptoms. In the secondary outcome of clinical response rates, NIBS treatment led to an increase in response rates (RR = 2.26, 95% CI: 1.57–3.25; p < 0.01).