Introduction:To investigate the effects of continuous (cTBS) and intermittent (iTBS) theta burst stimulation applied over the lateral cerebellum on corticospinal excitability in healthy individuals. Methods:Twenty right-handed healthy male participants underwent three TBS sessions (cTBS, iTBS, sham) in a randomized crossover design. Motor evoked potentials (MEPs), resting and active motor threshold (RMT and AMT, respectively), and cortical silent period (CSP) were assessed before and after each session using single-pulse transcranial magnetic stimulation over the left primary motor cortex. Transcranial magnetic stimulation was delivered to the right cerebellar hemisphere at 80% of active motor threshold. Results:A significant reduction in MEP amplitude was observed following iTBS (p=0.028), while no significant changes occurred after cTBS or sham stimulation. No significant effects were found in RMT or CSP across any of the protocols. All sessions were well tolerated and considered safe. Mild and transient side effects, such as neck discomfort or headache, were reported in five participants. Conclusion:Intermittent cerebellar TBS was associated with reduced MEP amplitude, suggesting decreased corticospinal excitability, whereas cTBS and sham stimulation did not produce significant effects. Cerebellar TBS was safe and well tolerated in all participants. These findings suggest that cerebellar iTBS may exert modulatory effects on motor cortical excitability and may contribute to a better understanding of cerebellar stimulation effects in healthy individuals.
Introduction:The presence of bipolar disorder (BD) in individuals with ASD exacerbates social and cognitive impairments, complicates diagnosis and treatment. The aim of this study was to compare the serum levels of specific miRNAs between children with ASD with and without BD, and to explore their association with BD comorbidity in ASD. Method:A group of 41 pediatric patients with comorbid ASD + BD and a group of 47 pediatric patients with ASD without BD were included in the study. Serum miRNA levels were measured using quantitative real-time polymerase chain reactions, focusing specifically on miRNAs such as miR-132-5p, miR-134-5p, miR-206, and miR-126-5p. Results:The ASD + BD group exhibited significantly greater ASD severity than the ASD without BD group. Serum levels of miR-134-5p, miR-206, and miR-126-5p were all higher in the ASD + BD group than in the ASD without BD group (p=0.038, p=0.023, and p=0.026, respectively), while miR-132-5p levels were not significantly different (p=0.105). Furthermore, miR-134-5p levels were correlated with the frequency of manic episodes in the ASD + BD group (p=0.007). Conclusion:The study findings suggest that miRNAs may be involved in the pathophysiology of comorbid BD in children with ASD and may potentially represent candidate biomarkers for early diagnosis and intervention, thus contributing to improved clinical outcomes in this population. Further research is now needed to validate these findings and to understand the underlying mechanisms.
Introduction:Repetitive Transcranial Magnetic Stimulation (rTMS) is an FDA-approved, non-invasive neuromodulation technique with clinically supported efficacy in the management of treatment-resistant major depressive disorder (TRD). Although the clinical effectiveness of high-frequency rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) is well established, the molecular mechanisms underlying its long-term therapeutic effects remain incompletely understood. The aim of this brief report is to examine the possible epigenetic modifications (DNA methylation, histone modifications, microRNA) associated with the antidepressant effects of rTMS in light of current literature, and to evaluate the dose-response relationship that may affect treatment response within the framework of homeostatic plasticity. Methods:A summary of current literature from the PubMed, Web of Science, and Google Scholar databases is presented using the keywords "rTMS," "major depression," "epigenetics," "histone modifications," "DNA methylation," "miRNA," and "homeostatic plasticity." Clinical and preclinical studies specifically investigating the molecular effects of rTMS on synaptic plasticity were included. Results:The reviewed studies suggest that rTMS may not merely provide transient electrical stimulation but may also operate through an "epigenetic regulatory" mechanism capable of permanently altering neuronal gene expression. In preclinical studies, changes in histone acetylation (e.g., regulation of CDK5 and PSD-95) and specific microRNAs (e.g., miR-146a-5p) have been observed to modulate synaptic plasticity. Furthermore, it has been proposed that the dose-response relationship of rTMS is non-linear; excessive stimulation may activate "homeostatic plasticity" mechanisms, thereby reducing synaptic sensitivity. Discussion:Current findings indicate that rTMS may exert an antidepressant effect by reorganizing synaptic plasticity through epigenetic modifications. Enhancing treatment efficacy depends on optimizing the dosage by considering homeostatic balances and integrating epigenetic biomarkers capable of predicting treatment response into clinical practice. Future personalized treatment protocols should be designed based on these molecular and neurophysiological insights.
Introduction:Approximately 20-30% of temporal lobe epilepsy (TLE) cases present with no visible abnormalities on conventional magnetic resonance imaging (MRI). When interictal electroencephalography (EEG) recordings are also persistently normal, the diagnosis and lateralization become major clinical challenges. We aimed to investigate whether automated hippocampal subfield volumetry could detect subtle structural alterations in these "electro-clinically silent" MRI-negative cases and to correlate these findings with seizure semiology. Methods:We analyzed 24 patients with clinically diagnosed MRI-negative/EEG-negative TLE and 26 age-matched healthy controls. Despite normal visual inspection on 1.5-T MRI, hippocampal subfield volumes were extracted using an automated segmentation pipeline (volBrain). Seizure semiology was systematically categorized to provide clinical-anatomical correlation. Results:TLE patients exhibited a significant and selective volume reduction in the right CA4-dentate gyrus (CA4-DG) subfield compared to healthy controls (p=0.003), even after adjusting for age, sex, and total intracranial volume (p=0.002). No statistically significant differences were observed in other hippocampal subfields (CA1, CA2/3, or subiculum), indicating a highly localized pattern of structural alteration. Conclusion:These results imply that selective CA4-DG atrophy is a defining characteristic of the MRI-negative TLE phenotype, thereby corroborating the "dentate gate" failure hypothesis. Quantitative volumetry provides a crucial diagnostic tool in settings with limited resources, where advanced techniques like 3-T MRI or invasive monitoring are not accessible. This objective structural marker, when integrated with comprehensive semiological analysis, improves diagnostic accuracy and facilitates early clinical intervention in difficult non-lesional TLE cases.
