BACKGROUND: The right inferior frontal gyrus (RIFG) is a potential beneficial brain stimulation target for autism. This randomized, double-blind, two-arm, parallel-group, sham-controlled clinical trial assessed the efficacy of intermittent theta burst stimulation (iTBS) over the RIFG in reducing autistic symptoms (NCT04987749).
METHODS: Conducted at a single medical center, the trial enrolled 60 intellectually able autistic individuals (aged 8-30 years; 30 active iTBS). The intervention comprised 16 sessions (two stimulations per week for eight weeks) of neuro-navigated iTBS or sham over the RIFG. Fifty-seven participants (28 active) completed the intervention and assessments at Week 8 (the primary endpoint) and follow-up at Week 12.
RESULTS: Autistic symptoms (primary outcome) based on the Social Responsiveness Scale decreased in both groups (significant time effect), but there was no significant difference between groups (null time-by-treatment interaction). Likewise, there was no significant between-group difference in changes in repetitive behaviors and exploratory outcomes of adaptive function and emotion dysregulation. Changes in social cognition (secondary outcome) differed between groups in feeling scores on the Frith-Happe Animations (Week 8, p = 0.026; Week 12, p = 0.025). Post-hoc analysis showed that the active group improved better on this social cognition than the sham group. Dropout rates did not vary between groups; the most common adverse event in both groups was local pain. Notably, our findings would not survive stringent multiple comparison corrections.
CONCLUSIONS: Our findings suggest that iTBS over the RIFG is not different from sham in reducing autistic symptoms and emotion dysregulation. Nonetheless, RIFG iTBS may improve social cognition of mentalizing others\' feelings in autistic individuals.

Transcranial temporal interference stimulation (tTIS) is a promising brain stimulation method that can target deep brain regions by delivering an interfering current from surface electrodes. Most instances of tTIS stimulate the brain with a single-frequency sinusoidal waveform generated by wave interference. Theta burst stimulation is an effective stimulation scheme that can modulate neuroplasticity by generating long-term potentiation- or depression-like effects. To broaden tTIS application, we developed a theta burst protocol using tTIS technique to modulate neuroplasticity in rats. Two cannula electrodes were unilaterally implanted into the intact skull over the primary motor cortex. Electrical field of temporal interference envelopes generated by tTIS through cannula electrodes were recorded from primary motor cortex. Theta burst schemes were characterized, and motor activation induced by the stimulation was also evaluated simultaneously by observing electromyographic signals from the corresponding brachioradialis muscle. After validating the stimulation scheme, we further tested the modulatory effects of theta burst stimulation delivered by tTIS and by conventional transcranial electrical stimulation on primary motor cortex excitability. Changes in the amplitude of motor evoked potentials, elicited when the primary motor cortex was activated by electrical pulses, were measured before and after theta burst stimulation by both techniques. Significant potentiation and suppression were found at 15 to 30 min after the intermittent and continuous theta burst stimulation delivered using tTIS, respectively. However, comparing to theta burst stimulations delivered using conventional form of transcranial electrical stimulation, using tTIS expressed no significant difference in modulating motor evoked potential amplitudes. Sham treatment from both methods had no effect on changing the motor evoked potential amplitude. The present study demonstrated the feasibility of using tTIS to achieve a theta burst stimulation scheme for motor cortical neuromodulation. These findings also indicated the future potential of using tTIS to carry out theta burst stimulation protocols in deep-brain networks for modulating neuroplasticity.

BACKGROUND: Previous studies have found that inhibitory priming with continuous theta burst stimulation (cTBS) can enhance the effect of subsequent excitatory conditioning stimuli with intermittent theta burst stimulation (iTBS) in the upper limbs. However, whether this combined stimulation approach elicits a comparable compensatory response in the lower extremities remains unclear. This study aimed to investigate how cTBS preconditioning modulated the effect of iTBS on motor cortex excitability related to the lower limb in healthy individuals.
METHODS: Using a randomised cross-over design, a total of 25 healthy participants (19 females, mean age = 24.80 yr) were recruited to undergo three different TBS protocols (cTBS + iTBS, sham cTBS + iTBS, sham cTBS + sham iTBS) in a random order. Each TBS intervention was administered with one-week intervals. cTBS and iTBS were administered at an intensity of 80% active motor threshold (AMT) delivering a total of 600 pulses. Before intervention (T0), immediately following intervention (T1), and 20 min after intervention (T2), the corticomotor excitability was measured for the tibialis anterior muscle of participants\' non-dominant leg using a Magneuro100 stimulator and matched double-cone coil. The average amplitude of the motor-evoked potential (MEP) induced by applying 20 consecutive monopulse stimuli at an intensity of 130% resting motor threshold (RMT) was collected and analysed.
RESULTS: Compare with T0 time, the MEP amplitude (raw and normalised) at T1 and T2 showed a statistically significant increase following the cTBS + iTBS protocol (p < 0.01), but no significant differences were observed in amplitude changes following other protocols (sham cTBS + iTBS and sham cTBS + sham iTBS) (p > 0.05). Furthermore, no statistically significant difference was found among the three protocols at any given time point (p > 0.05).
CONCLUSIONS: Preconditioning the lower extremity motor cortex with cTBS prior to iTBS intervention can promptly enhance its excitability in healthy participants. This effect persists for a minimum duration of 20 min.
BACKGROUND: No: ChiCTR2300069315. Registered 13 March, 2023, https://www.chictr.org.cn.

BACKGROUND: Sex- and age-dependent outcome differences have been observed in treatment of Major Depressive Disorder (MDD), including 10 Hz repetitive Transcranial Magnetic Stimulation (rTMS). We examined whether there are sex- and age-dependent differences in outcome with intermittent Theta Burst Stimulation (iTBS), another rTMS protocol.
METHODS: The relationship between biological sex, age, and treatment outcome was retrospectively examined among 414 patients with MDD treated with 10 Hz or iTBS rTMS. Linear mixed-effects modeling was used to examine the association between treatment and change in the 30-item Inventory of Depressive Symptomatology Self-Report (IDS-SR30) score from baseline to treatments 10 and 30, with biological sex (M/F), protocol (iTBS/10 Hz), age (≥/<50 years old), and time (treatment 1/10/30) included as fixed effects. The three-way sex-protocol-time and age-protocol-time interactions were used to determine any differential relationships between protocol and outcome dependent on sex and age. Post-hoc t-tests were conducted to examine differences in improvement.
RESULTS: There was a significant three-way sex-protocol-time interaction at treatments 10 (p = 0.016) and 30 (p = 0.031). Males showed significantly greater improvement with iTBS than females at treatments 10 (p = 0.041) and 30 (p = 0.035), while females showed numerically greater improvement with 10 Hz treatment. While there was not a significant three-way age-protocol-time interaction, there was a significant interaction between age (≥50 years old) and time at treatments 10 (p = 0.007) and 30 (p = 0.042), and among age, sex, and time at treatment 30 (p = 0.028).
CONCLUSIONS: Retrospective naturalistic treatment protocol.
CONCLUSIONS: iTBS appeared less efficacious in females than in males, and rTMS overall was more efficacious in patients over fifty, particularly females.

Working memory refers to the process of temporarily storing and manipulating information. The role of the cerebellum in working memory is thought to be achieved through its connections with the prefrontal cortex. Previous studies showed that theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation, of the cerebellum changes its functional connectivity with the prefrontal cortex. Specifically, excitatory intermittent TBS (iTBS) increases, whereas inhibitory continuous TBS (cTBS) decreases this functional connectivity. We hypothesized that iTBS on the cerebellum will improve working memory, whereas cTBS will disrupt it. Sixteen healthy participants (10 women) participated in this study. Bilateral cerebellar stimulation was applied with a figure-of-eight coil at 3 cm lateral and 1 cm below the inion. The participants received iTBS, cTBS, and sham iTBS in three separate sessions in random order. Within 30 min after TBS, the participants performed four working memory tasks: letter 1-Back and 2-Back, digit span forward, and digit span backward. Repeated measures analysis of variance revealed a significant effect of the type of stimulation (iTBS/cTBS/Sham) on performance in the digit span backward task (p = 0.02). The planned comparison showed that the cTBS condition had significantly lower scores than the sham condition (p = 0.01). iTBS and cTBS did not affect performance in the 1- and 2-Back and the digit span forward tasks compared to sham stimulation. The findings support the hypothesis that the cerebellum is involved in working memory, and this contribution may be disrupted by cTBS.

Scarce clinical trials involving autistic people with intellectual disability (ID) and minimally speaking (MS) status have been a substantial unmet research need in the field. Although earlier studies have demonstrated the feasibility and beneficial potentials of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in intellectually able autistic people, the feasibility and tolerability of applying rTMS in autistic people with ID/MS has never been studied. We conducted the world-first 4-week randomized, double-blind, sham-controlled pilot trial to investigate the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS, a variant of excitatory rTMS) over the left DLPFC in autistic youth with ID/MS. 25 autistic youth with ID/MS (aged 8-30 years) were randomized to a 20-session 4-week daily iTBS (n = 13) vs. sham stimulation (n = 12) with follow-up 4 and 8 weeks, respectively, after the last stimulation. A retention rate was 100% in our study. Adverse events of local pain (38%) and dizziness (8%) were only noted in the active group. All adverse events were mild and transient. There were no seizures, new behavioral problems, or other severe/serious adverse events noted. No participants dropped out due to adverse events. With a small sample size, we did not find any beneficial signal of DLPFC iTBS. Our pilot data suggest regular daily TBS treatment for four weeks is feasible, well tolerated and safe in autistic youth with ID/MS. Future randomized controlled trials with sufficiently powered samples are needed to investigate the beneficial potential of rTMS/TBS for autistic people with ID/MS.

Theta burst stimulation (TBS) is a non-invasive brain stimulation technique that can modulate neural activity. The effect of TBS on regions beyond the motor cortex remains unclear. With increased interest in applying TBS to non-motor regions for research and clinical purposes, these effects must be understood and characterised. We synthesised the electrophysiological effects of a single session of TBS, as indexed by electroencephalography (EEG) and concurrent transcranial magnetic stimulation and EEG (TMS-EEG), in non-clinical participants. We reviewed 79 studies that administered either continuous TBS (cTBS) or intermittent TBS (iTBS) protocols. Broadly, cTBS suppressed and iTBS facilitated evoked response component amplitudes. Response to TBS as measured by spectral power and connectivity was much more variable. Variability increased in the presence of task stimuli. There was a large degree of heterogeneity in the research methodology across studies. Additionally, the effect of individual differences on TBS response is insufficiently investigated. Future research investigating the effects of TBS as measured by EEG must consider methodological and individual factors that may affect TBS outcomes.

Schizophrenia is a chronic psychiatric disorder severely affecting patients\' functioning and quality of life. Unlike positive symptoms, cognitive impairment and negative symptoms cannot be treated pharmacologically and represent consistent predictors of the illness\'s prognosis. Cognitive remediation (CR) interventions have been applied to target these symptoms. Brain stimulation also provides promising yet preliminary results in reducing negative symptoms, whereas its effect on cognitive impairment remains heterogeneous. Here, we combined intermittent theta burst stimulation (iTBS) with CR to improve negative symptoms and cognitive impairment in schizophrenia spectrum patients. One hundred eligible patients were invited, and twenty-one participated. We randomized them into four groups, manipulating the stimulation condition (real vs. sham) and CR (no training vs. training). We delivered fifteen iTBS sessions over the left dorsolateral prefrontal cortex for three weeks, followed (or not) by 50 min of training. Consensus-based clinical and cognitive assessment was administered at baseline and after the treatment, plus at three follow-ups occurring one, three, and six months after the intervention. Mixed-model analyses were run on cognitive and negative symptom scores. The preliminary findings highlighted a marginal modulation of iTBS on negative symptoms, whereas CR improved isolated cognitive functions. We herein discuss the limitations and strengths of the methodological approach.

The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95 % confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3 + ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = - 1.40, 95 %CIs = - 2.67 to - 0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.

OBJECTIVE: Transcranial magnetic stimulation (TMS) can efficiently and robustly modulate synaptic plasticity, but little is known about how TMS affects functional connectivity (rs-fMRI). Accordingly, this project characterized TMS-induced rsFC changes in depressed patients who received 3 days of left prefrontal intermittent theta burst stimulation (iTBS).
METHODS: rs-fMRI was collected from 16 subjects before and after iTBS. Correlation matrices were constructed from the cleaned rs-fMRI data. Electric-field models were conducted and used to predict pre-post changes in rs-fMRI. Site by orientation heatmaps were created for vectors centered on the stimulation site and a control site (contralateral motor cortex).
RESULTS: For the stimulation site, there was a clear relationship between both site and coil orientation, and connectivity changes. As distance from the stimulation site increased, prediction accuracy decreased. Similarly, as eccentricity from the optimal orientation increased, prediction accuracy decreased. The systematic effects described above were not apparent in the heatmap centered on the control site.
CONCLUSIONS: These results suggest that rs-fMRI following iTBS changes systematically as a function of the distribution of electrical energy delivered from the TMS pulse, as represented by the e-field model.
CONCLUSIONS: This finding lays the groundwork for future studies to individualize TMS targeting based on how predicted rs-fMRI changes might impact psychiatric symptoms.