Unlocking the Potential of Repetitive Transcranial Magnetic Stimulation in Alzheimer's Disease: A Meta-Analysis of Randomized Clinical Trials to Optimize Intervention Strategies.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an advanced and noninvasive technology that uses pulse stimulation to treat cognitive impairment. However, its specific effects have always been mixed with those of cognitive training, and the optimal parameter for Alzheimer's disease (AD) intervention is still ambiguous. Objective: This study aimed to summarize the therapeutic effects of pure rTMS on AD, excluding the influence of cognitive training, and to develop a preliminary rTMS treatment plan. Methods: Between 1 January 2010 and 28 February 2023, we screened randomized controlled clinical trials from five databases (PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials. gov). We conducted a meta-analysis and systematic review of treatment outcomes and rTMS treatment parameters. Result: A total of 4,606 articles were retrieved. After applying the inclusion and exclusion criteria, 16 articles, comprising 655 participants (308 males and 337 females), were included in the final analysis. The findings revealed that rTMS significantly enhances both global cognitive ability (p = 0.0002, SMD = 0.43, 95% CI = 0.20-0.66) and memory (p = 0.009, SMD = 0.37, 95% CI = 0.09-0.65). Based on follow-up periods of at least 6 weeks, the following stimulation protocols have demonstrated efficacy for AD: stimulation sites (single or multiple targets), frequency (20 Hz), stimulation time (1-2 s), interval (20-30 s), single pulses (≤2500), total pulses (>20000), duration (≥3 weeks), and sessions (≥20). Conclusions: This study suggests that rTMS may be an effective treatment option for patients with AD, and its potential therapeutic capabilities should be further developed in the future.

Predicting response to repetitive transcranial magnetic stimulation in patients with chronic insomnia disorder using electroencephalography: A pilot study.

Predicting responsvienss to repetitive transcranial magnetic stimulation (rTMS) can facilitate personalized treatments with improved efficacy; however, predictive features related to this response are still lacking. We explored whether resting-state electroencephalography (rsEEG) functional connectivity measured at baseline or during treatment could predict the response to 10-day rTMS targeted to the right dorsolateral prefrontal cortex (DLPFC) in 36 patients with chronic insomnia disorder (CID). Pre- and post-treatment rsEEG scans and the Pittsburgh Sleep Quality Index (PSQI) were evaluated, with an additional rsEEG scan conducted after four rTMS sessions. Machine-learning approaches were employed to assess the ability of each connectivity measure to distinguish between responders (PSQI improvement > 25%) and non-responders (PSQI improvement ≤ 25%). Furthermore, we analyzed the connectivity trends of the two subgroups throughout the treatment. Our results revealed that the machine learning model based on baseline theta connectivity achieved the highest accuracy (AUC = 0.843) in predicting treatment response. Decreased baseline connectivity at the stimulated site was associated with higher responsiveness to TMS, emphasizing the significance of functional connectivity characteristics in rTMS treatment. These findings enhance the clinical application of EEG functional connectivity markers in predicting treatment outcomes.

Functional connectivity changes are correlated with sleep improvement in chronic insomnia patients after rTMS treatment.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited. Objective: This study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS. Methods: Thirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI). Results: After treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8-10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment. Conclusion: Based on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization.

The Effect of Multiple Factors on Working Memory Capacities: Aging, Task Difficulty, and Training.

GOAL: Working memory (WM) is a memory system with a limited capacity that can process and store information temporarily in the performing of cognitive tasks. Despite WM is known to be influenced by age, the difficulty of tasks and trained or not from behavior studies, little is known about their relationships from the aspect of the brain functional network. Our goal was to explore the factor of aging-related changes of WM with brain functional networks. METHODS: In this study, 25 healthy elderly and 23 healthy young volunteers were recruited for electroencephalogram (EEG) recording during the visual WM task with four difficulty levels (1-4 backs). In each back, we repeat the experiment with four sessions, and we add training sections between session one and session two as well as between session two and session three. However, we remove any training section between session three and session four in order to evaluate the impact of forgetting on WM in different age groups. After the experiment, we utilized graph theoretical analysis to characterize the brain functional network in three frequency bands (alpha, beta, and theta). RESULTS: From the well-designed experiment, we found that physiological aging influences brain network connectivity and makes the functional brain network less differentiated. Moreover, there is an inverse relationship between alpha activity and WM load for the elderly group, which is absent in the young group. At the same time, theta band activity will be correlated with behavioral performance for the elderly group with WM training between sessions, which is also absent in the young group. To further study the influence of difficulty of tasks and training on the WM, we distinguish the tasks with quantified topological characteristics, and the classification results manifest that the training is more effective for the young group. Finally, through the establishment of a brain map before and after training, we find that the right parietal lobe plays an important role in the training of WM for the elderly group whereas the beta band plays an important role in WM for both the elderly group and the young group. CONCLUSION: Taken together, our findings clarify the underlying mechanism of WM under different frequency bands in terms of physiological aging, the influence of training, and task difficulty. SIGNIFICANCE: the working memory capacities can be uncovered in terms of the combination of three-way ANOVA and EEG-based graph theoretical analysis.

Dual-targeted repetitive transcranial magnetic stimulation modulates brain functional network connectivity to improve cognition in mild cognitive impairment patients.

Background: Mild cognitive impairment (MCI) is a condition between normal aging and dementia; nearly 10-15% of MCI patients develop dementia annually. There are no effective interventions for MCI progression. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has attempted to improve the overall cognitive function of MCI patients. However, it does not affect episodic memory improvement. Methods: In this study, we engaged 15 clinically diagnosed MCI patients and normal controls to explore the effect of dual-targeted rTMS on progressing cognitive function, particularly episodic memory in MCI patients. Resting-state EEG recordings and neuropsychological assessments were conducted before and after the intervention. EEG features were extracted using an adaptive algorithm to calculate functional connectivity alterations in relevant brain regions and the mechanisms of altered brain functional networks in response to dual-target rTMS. Results: The study revealed that the functional brain connectivity between the right posterior cingulate gyrus (PCC) and the right dorsal caudate nucleus (DC) was significantly reduced in MCI patients compared to normal controls (p < 0.001). Dual-target rTMS increased the strength of the reduced functional connectivity (p < 0.001), which was related to cognitive enhancement (p < 0.05). Conclusion: This study provides a new stimulation protocol for rTMS intervention. Improving the functional connectivity of the right PCC to the right DC is a possible mechanism by which rTMS improves overall cognitive and memory function in MCI patients.

The Effect of Longitudinal Training on Working Memory Capacities: An Exploratory EEG Study.

The study of working memory (WM) is a hot topic in recent years and accumulating literatures underlying the achievement and neural mechanism of WM. However, the effect of WM training on cognitive functions were rarely studied. In this study, nineteen healthy young subjects participated in a longitudinal design with one week N-back training (N=1,2,3,4). Experimental results demonstrated that training procedure could help the subjects master more complex psychological tasks when comparing the pre-training performance with those post-training. More specifically, the behavior accuracy increased from 68.14±9.34%, 45.09±14.90%, 39.12±12.71%, and 32.11±10.98% for 1-back, 2-back, 3-back and 4-back respectively to 73.52±4.01%, 69.14±5.28%, 69.09±6.41% and 64.41±5.12% after training. Furthermore, we applied electroencephalogram (EEG) power and functional connectivity to reveal the neural mechanisms of this beneficial effect and found that the EEG power of δ, θ and α band located in the left temporal and occipital lobe increased significantly. Meanwhile, the functional connectivity strength also increased obviously in δ and θ band. In sum, we showed positive effect of WM training on psychological performance and explored the neural mechanisms. Our findings may have the implications for enhancing the performance of participants who are prone to cognitive.