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Paired stimulation of the brain and spinal cord can remodel the central nervous tissue circuitry in an animal model to induce motor neuroplasticity. The effects of simultaneous stimulation vary according to the extent and severity of spinal cord injury. Therefore, our study aimed to determine the significant effects on an incomplete SCI rat brain and spinal cord through 3 min and 20 min stimulations after 4 weeks of intervention. Thirty-three Sprague Dawley rats were classified into six groups: (1) normal, (2) sham, (3) iTBS/tsDCS, (4) iTBS/ts-iTBS, (5) rTMS/tsDCS, and (6) rTMS/ts-iTBS. Paired stimulation of the brain cortex and spinal cord thoracic (T10) level was applied simultaneously for 3–20 min. The motor evoked potential (MEP) and Basso, Beattie, and Bresnahan (BBB) scores were recorded after every week of intervention for four weeks along with wheel training for 20 min. Three-minute stimulation with the iTBS/tsDCS intervention induced a significant (p < 0.050 *) increase in MEP after week 2 and week 4 treatments, while 3 min iTBS/ts-iTBS significantly improved MEP (p < 0.050 *) only after the week 3 intervention. The 20 min rTMS/ts-iTBS intervention showed a significant change only in post_5 min after week 4. The BBB score also changed significantly in all groups except for the 20 min rTMS/tsDCS intervention. iTBS/tsDCS and rTMS/ts-iTBS interventions induce neuroplasticity in an incomplete SCI animal model by significantly changing electrophysiological (MEP) and locomotion (BBB) outcomes.

Aims Working memory (WM), a short‐term cognitive process involving the prefrontal cortex, is critical for daily functioning. This study investigated the effects of iTBS on WM performance and its neural mechanisms in healthy adults. Methods Thirty‐one healthy adults completed 1‐back and 2‐back tasks while undergoing EEG recording. Each received both active and sham iTBS over the left dorsolateral prefrontal cortex separately. Behavioral performance, EEG power, and functional connectivity were analyzed. Results Active iTBS significantly increased theta power in prefrontal cortices during the 1‐back task. It also enhanced alpha band connectivity between the left prefrontal and right parietal cortices. In the 2‐back task, iTBS increased beta band connectivity between the right prefrontal and right parietal cortices, and alpha band connectivity between the left and right parietal cortices. No significant behavioral differences were found. Conclusion These findings suggest that iTBS effects on WM are primarily reflected in large‐scale oscillatory network dynamics, rather than solely in localized cortical activity or behavioral performance. This study explores the effects of intermittent theta burst stimulation (iTBS) on working memory in healthy adults. iTBS modulated neural oscillatory networks, enhancing theta and alpha connectivity between prefrontal and parietal cortices, but no significant behavioral differences were observed.

BackgroundHuntington’s disease is a rare neurodegenerative movement disorder characterized by early disruption of frontostriatal systems, affecting motor, cognitive, and affective domains. Non-invasive brain stimulation targeting prefrontal networks may offer a means to modulate these distributed systems, although controlled evidence in Huntington’s disease remains limited, particularly for accelerated stimulation protocols.ObjectiveTo investigate whether accelerated intermittent theta-burst stimulation (iTBS) applied to the dorsolateral prefrontal cortex is associated with behavioral, motor and electrophysiological changes reflecting modulation of prefrontal network function in early-stage Huntington’s disease.MethodsTen patients with genetically confirmed Huntington’s disease participated in a within-subject, fixed-order longitudinal study, which included a sham exposure phase followed by active stimulation. Assessments were conducted at baseline (T0), after sham stimulation (T1), after active accelerated iTBS (T2), and at 60-day follow-up (T3). Clinical scales for motor impairment, behavioral measures targeting executive, affective, and social-cognitive domains were combined with event-related potentials (ERPs) recorded during cognitive and emotional Stroop tasks. The fixed-order design was chosen to minimize potential carry-over effects associated with accelerated stimulation protocols.ResultsNo significant behavioral or electrophysiological changes were observed during the sham exposure phase. In contrast, active iTBS was associated with domain-specific behavioral changes, particularly in affective, executive, and social-cognitive domains, accompanied by changes in event-related potential activity, particularly within delayed N200-related responses during emotional interference. Effects were domain-specific and were not associated with normalization of electrophysiological latency profiles. Motor scales were not modified by either sham or real stimulation.ConclusionAccelerated prefrontal iTBS was associated with behavioral and electrophysiological changes following active stimulation of prefrontal network in Huntington’s disease. These findings support the feasibility of targeting distributed non-motor circuits in HD and designs accounting for cumulative and time-dependent effects of stimulation in early-phase neuromodulation studies.

Intermittent theta burst stimulation (iTBS) is a promising noninvasive therapy to restore the excitability of the cortex, and subsequently improve the function of the upper extremities. Several studies have demonstrated the effectiveness of iTBS in restoring upper limb function and modulating cortical excitability. We aimed to evaluate the effects of iTBS on upper limb motor recovery after stroke.BackgroundIntermittent theta burst stimulation (iTBS) is a promising noninvasive therapy to restore the excitability of the cortex, and subsequently improve the function of the upper extremities. Several studies have demonstrated the effectiveness of iTBS in restoring upper limb function and modulating cortical excitability. We aimed to evaluate the effects of iTBS on upper limb motor recovery after stroke.The purpose of this article is to evaluate the influence of intermittent theta-burst stimulation on upper limb motor recovery and improve the quality of life.ObjectiveThe purpose of this article is to evaluate the influence of intermittent theta-burst stimulation on upper limb motor recovery and improve the quality of life.A literature search was conducted using PubMed, EMBASE, MEDLINE, The Cochrane Library, Web of Science, and CBM, including only English studies, to identify studies that investigated the effects of iTBS on upper limb recovery, compared with sham iTBS used in control groups. Effect size was reported as standardized mean difference (SMD) or weighted mean difference (WMD).MethodA literature search was conducted using PubMed, EMBASE, MEDLINE, The Cochrane Library, Web of Science, and CBM, including only English studies, to identify studies that investigated the effects of iTBS on upper limb recovery, compared with sham iTBS used in control groups. Effect size was reported as standardized mean difference (SMD) or weighted mean difference (WMD).Ten studies were included in the meta-analysis. The results of the meta-analysis indicated that when compared to the control group, the iTBS group had a significant difference in the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT) (WMD: 3.20, 95% CI: 1.42 to 4.97; WMD: 3.72, 95% CI: 2.13 to 5.30, respectively). In addition, there was also a significant improvement in the modified Ashworth scale (MAS) compared to the sham group (WMD: -0.56; 95% CI: -0.85 to -0.28). More evidence is still needed to confirm the effect of Barthel Index (BI) scores after interventions. However, no significant effect was found for the assessment of Motor Evoked Potential (MEP) amplitude and MEP latency (SMD: 0.35; 95% CI: -0.21 to 0.90; SMD: 0.35, 95% CI: -0.18 to 0.87; SMD: 0.03, 95% CI: -0.49 to 0.55; respectively).ResultsTen studies were included in the meta-analysis. The results of the meta-analysis indicated that when compared to the control group, the iTBS group had a significant difference in the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT) (WMD: 3.20, 95% CI: 1.42 to 4.97; WMD: 3.72, 95% CI: 2.13 to 5.30, respectively). In addition, there was also a significant improvement in the modified Ashworth scale (MAS) compared to the sham group (WMD: -0.56; 95% CI: -0.85 to -0.28). More evidence is still needed to confirm the effect of Barthel Index (BI) scores after interventions. However, no significant effect was found for the assessment of Motor Evoked Potential (MEP) amplitude and MEP latency (SMD: 0.35; 95% CI: -0.21 to 0.90; SMD: 0.35, 95% CI: -0.18 to 0.87; SMD: 0.03, 95% CI: -0.49 to 0.55; respectively).Our results showed that iTBS significantly improved motor impairment, functional activities, and reduced muscle tone of upper limbs, thereby increasing the ability to perform Activities of Daily Living (ADL) in stroke patients, while there were no significant differences in MEPs. In conclusion, iTBS is a promising non-invasive brain stimulation as an adjunct to therapy and enhances the therapeutic effect of conventional physical therapy. In the future, more randomized controlled trials with large sample sizes, high quality, and follow-up are necessary to explore the neurophysiological effects.ConclusionOur results showed that iTBS significantly improved motor impairment, functional activities, and reduced muscle tone of upper limbs, thereby increasing the ability to perform Activities of Daily Living (ADL) in stroke patients, while there were no significant differences in MEPs. In conclusion, iTBS is a promising non-invasive brain stimulation as an adjunct to therapy and enhances the therapeutic effect of conventional physical therapy. In the future, more randomized controlled trials with large sample sizes, high quality, and follow-up are necessary to explore the neurophysiological effects.https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392739.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392739.

Objective Theta-burst stimulation, including intermittent (iTBS) and continuous (cTBS) protocols, is a promising neuromodulatory intervention for autism spectrum disorder (ASD). This study aims to elucidate the therapeutic mechanisms of iTBS and cTBS for ASD. Methods Prenatal valproic acid-induced ASD rats were established and were randomized into VPA, VPA + iTBS, and VPA + cTBS groups, with a saline group as control. Core and comorbid ASD behaviors in rats were assessed. Multi-omics analyses included 16 S rRNA sequencing of cecal contents, non-targeted fecal metabolomics, and prefrontal cortex transcriptomics. Key pathways were validated via Western blot, ELISA, and immunofluorescence. Integrative analyses correlated multi-omics data with neuroendocrine findings. Results Behavioral assessments demonstrated that both iTBS and cTBS significantly ameliorated social deficits and repetitive behaviors in VPA-exposed rats. However, protocol-specific effects on comorbidities were observed: cTBS, but not iTBS, effectively alleviated anxiety-like behaviors, whereas iTBS, but not cTBS, significantly improved learning and memory. The multi-omics approach demonstrated that iTBS primarily modulated inflammatory immune responses and energy metabolism, while cTBS predominantly regulated oxidative stress, lipid metabolism, and nucleotide metabolism. Both interventions suppressed the hyperactivated PI3K/AKT/mTOR signaling pathway, an effect potentially linked to the normalization of hypothalamic-pituitary axis function. Furthermore, we identified a potential interplay between the GH/IGF-1 axis and the gut microbiome in ASD, which was differentially modulated by iTBS and cTBS. Conclusion iTBS modulated inflammatory-immune responses and energy metabolism, while cTBS regulated oxidative stress, lipid metabolism, and nucleotide metabolism. The inhibition of the central GH/PI3K/AKT/mTOR pathway by both protocols may involve their specific regulation of distinct gut microbiota communities. Graphical Abstract

Objectives: The objective of this study was to explore the efficacy of cerebellar intermittent theta burst stimulation (iTBS) on the walking function of stroke patients. Methods: Stroke patients with walking dysfunction aged 25–80 years who had suffered their first unilateral stroke were included. A total of 36 patients [mean (SD) age, 53 (7.93) years; 10 women (28%)] were enrolled in the study. All participants received the same conventional physical therapy, including transfer, balance, and ambulation training, during admission for 50 min per day during 2 weeks (10 sessions). Every session was preceded by 3 min procedure of cerebellar iTBS applyed over the contralesional cerebellum in the intervention group or by a similar sham iTBS in control group. The groups were formed randomly and the baseline characteristics showed no significant difference. The primary outcome measure was Fugl–Meyer Assessment–Lower Extremity scores. Secondary outcomes included walking performance and corticospinal excitability. Measures were performed before the intervention beginning (T0), after the first (T1) and the second (T2) weeks. Results: The Fugl–Meyer Assessment for lower extremity scores slightly improved with time in both groups with no significant difference between the groups and over the time. The walking performance significantly improved with time and between group. Two-way mixed measures ANOVA showed that there was significant interaction between time and group in comfortable walking time ( F 2,68 = 6.5242, P = 0.0080, η 2 partial = 0.276, ε = 0.641), between-group comparisons revealed significant differences at T1 ( P = 0.0072) and T2 ( P = 0.0133). The statistical analysis of maximum walking time showed that there was significant interaction between time and groups ( F 2,68 = 5.4354, P = 0.0115, η 2 partial = 0.198, ε = 0.734). Compared with T0, the differences of maximum walking time between the two groups at T1 ( P = 0.0227) and T2 ( P = 0.0127) were statistically significant. However, both the Timed up and go test and functional ambulation category scale did not yield significant differences between groups ( P > 0.05). Conclusion: Our results revealed that applying iTBS over the contralesional cerebellum paired with physical therapy could improve walking performance in patients after stroke, implying that cerebellar iTBS intervention may be a noninvasive strategy to promote walking function in these patients. This study was registered at ChiCTR, number ChiCTR1900026450.

Stroke is characterized by high morbidity and high disability rate, and is the main cause of long-term disability. To evaluate the efficacy of intermittent theta burst stimulation (iTBS) on patients with lower limb motor dysfunction after stroke through functional near-infrared spectroscopy (fNIRS) and the Fugl-Meyer Assessment of Lower Extremity Motor Function Scale, and analyze the activation of each channel of the cerebral cortex through fNIRS. Sixty-six patients were randomly assigned (1:1) to a control group (  = 33) or an iTBS treatment group (  = 33). The control group was given basic rehabilitation treatment and sham stimulation of iTBS, while the treatment group was given basic rehabilitation treatment and real stimulation of iTBS. After treatment, when comparing the treatment group and the control group, there was a statistically significant difference in the scores of the Fugl-Meyer Lower Limb Motor Function Assessment Scale. After 4 weeks of treatment, when comparing the treatment group and the control group, there were statistically significant differences in task-related activation in channels over the ipsilesional premotor cortex (PMC) and primary motor cortex (M1), and the contralesional primary somatosensory cortex (S1) (  < 0.05). In the treatment group, task-related activation in channels over ipsilesional PMC and M1 and contralesional S1 was also significantly increased compared with baseline (  < 0.05). iTBS has a certain curative effect in the treatment of lower limb dysfunction after stroke. On fNIRS, increased activation was observed in channels over ipsilesional PMC and M1 and contralesional S1.

Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas through magnetic pulses. Numerous studies indicated beneficial effect of rTMS in several neurological diseases, including AD, however exact mechanism are yet to be elucidated. We aimed to evaluate the effect of intermittent theta burst stimulation (iTBS), an rTMS paradigm, on behavioral, neurochemical and molecular level in trimethyltin (TMT)-induced Alzheimer’s-like disease model. TMT acts as a neurotoxic agent targeting hippocampus causing cognitive impairment and neuroinflammation, replicating behavioral and molecular aspects of AD. Male Wistar rats were divided into four experimental groups –controls, rats subjected to a single dose of TMT (8 mg/kg), TMT rats subjected to iTBS two times per day for fifteen days and TMT sham group. After three weeks, we examined exploratory behavior and memory, histopathological and changes on molecular level. TMT-treated rats exhibited severe and cognitive deficit. iTBS-treated animals showed improved cognition. iTBS reduced TMT-induced inflammation and increased anti-inflammatory molecules. We examined PI3K/Akt/mTOR signaling pathway which is involved in regulation of apoptosis, cell growth and learning and memory. We found significant downregulation of phosphorylated forms of Akt and mTOR in TMT-intoxicated animals, which were reverted following iTBS stimulation. Application of iTBS produces beneficial effects on cognition in of rats with TMT-induced hippocampal neurodegeneration and that effect could be mediated via PI3K/Akt/mTOR signaling pathway, which could candidate this protocol as a potential therapeutic approach in neurodegenerative diseases such as AD.

Repetitive transcranial magnetic stimulation has been employed to treat drug dependence, reduce drug use and improve cognition. The aim of the study was to analyze the effectiveness of intermittent theta-burst stimulation (iTBS) on cognition in individuals with methamphetamine use disorder (MUD). This was a secondary analysis of 40 MUD subjects receiving left dorsolateral prefrontal cortex (L-DLPFC) iTBS or sham iTBS for 20 times over 10 days (twice-daily). Changes in working memory (WM) accuracy, reaction time, and sensitivity index were analyzed before and after active and sham rTMS treatment. Resting-state EEG was also acquired to identify potential biological changes that may relate to any cognitive improvement. The results showed that iTBS increased WM accuracy and discrimination ability, and improved reaction time relative to sham iTBS. iTBS also reduced resting-state delta power over the left prefrontal region. This reduction in resting-state delta power correlated with the changes in WM. Prefrontal iTBS may enhance WM performance in MUD subjects. iTBS induced resting EEG changes raising the possibility that such findings may represent a biological target of iTBS treatment response.