OBJECTIVE: The dorsolateral prefrontal cortex (DLPFC) is implicated in pain modulation, suggesting its potential as a therapeutic target for pain relief. However, studies on transcranial electrical stimulation (tES) over the DLPFC yielded diverse results, likely due to differences in stimulation protocols or pain assessment methods. This study aims to evaluate the analgesic effects of DLPFC-tES using a meta-analytical approach.
METHODS: A meta-analysis of 29 studies involving 785 participants was conducted. The effects of genuine and sham DLPFC-tES on pain perception were examined in healthy individuals and patients with clinical pain. Subgroup analyses explored the impact of stimulation parameters and pain modalities.
RESULTS: DLPFC-tES did not significantly affect pain outcomes in healthy populations but showed promise in reducing pain-intensity ratings in patients with clinical pain (Hedges\' g = -0.78, 95% CI = [-1.33, -0.24], p = 0.005). Electrode placement significantly influenced the analgesic effect, with better results observed when the anode was at F3 and the cathode at F4.
CONCLUSIONS: DLPFC-tES holds potential as a cost-effective pain management option, particularly for clinical populations. Optimizing electrode placement, especially with an symmetrical configuration, may enhance therapeutic efficacy. These findings underscore the promise of DLPFC-tES for alleviating perceived pain intensity in clinical settings, emphasizing the importance of electrode placement optimization.

BACKGROUND: Our previous study synthesized the analgesic effects of repetitive Transcranial Magnetic Stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) trials up to 2019. There has been a significant increase in pain trials in the past few years, along with methodological variabilities such as sample size, stimulation intensity, and rTMS paradigms.
OBJECTIVE: This study therefore updated the effects of DLPFC-rTMS on chronic pain and quantified the impact of methodological differences across studies.
RESULTS: A total of 36 studies were included. Among them, 26 studies were clinical trials (update = 9, 307/711 patients), and 10 (update = 1, 34/249 participants) were provoked pain studies. The updated meta-analysis does not support an effect on neuropathic pain after including the additional trials (pshort-term = 0.20, pmid-term = 0.50). However, there is medium-to-large analgesic effect in migraine trials extending up to six weeks follow-up (SMDmid-term = -0.80, SMDlong-term = -0.51), that was not previously reported. Methodological differences wthine the studies were considered. DLPFC-rTMS also induces potential improvement in the emotional aspects of pain (SMDshort-term = -0.28).
CONCLUSIONS: The updated systematic meta-analysis continues to support analgesic effects for chronic pain overall. However, the updated results no longer support DLPFC-rTMS for pain relief in neuropathic pain, and do supports DLPFC-rTMS in the management of migraine. There is also evidence for DLPFC-rTMS to improve emotional aspects of pain.

Depressive and anxiety symptoms are prevalent among patients with various clinical conditions, resulting in diminished emotional well-being and impaired daily functioning. The neural mechanisms underlying these symptoms, particularly across different disorders, remain unclear, limiting the effectiveness of conventional treatments. Therefore, it is crucial to elucidate the neural underpinnings of depressive and anxiety symptoms and investigate novel, effective treatments across clinical conditions. Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that can help understand the neural underpinnings of symptoms and facilitate the development of interventions, addressing the two research gaps at both neural and clinical levels. Thus, this systematic review and meta-analysis aims to evaluate the existing evidence regarding the therapeutic efficacy of tDCS in reducing depressive and anxiety symptoms among individuals with diverse clinical diagnoses. This review evaluated evidence from fifty-six randomized, sham-controlled trials that administered repeated tDCS sessions with a parallel design, applying a three-level meta-analytic model. tDCS targeting the left dorsolateral prefrontal cortex (DLPFC) at 2-mA intensity demonstrates moderate efficacy in alleviating depressive symptoms, identifying the left DLPFC as a transdiagnostic neural mechanism of depressive symptoms across clinical conditions. In comparison, the findings on anxiety symptoms demonstrate greater heterogeneity. tDCS over the left DLPFC is effective in reducing depressive symptoms and shows promising effects in alleviating anxiety symptoms among individuals with diverse diagnoses. These findings enhance our understanding of the neuropsychological basis of depressive and anxiety symptoms, laying the groundwork for the development of more effective tDCS interventions applicable across clinical conditions.

UNASSIGNED: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are increasingly used for major depressive disorder (MDD). Most tDCS and rTMS studies target the left dorsolateral prefrontal cortex, either with or without neuronavigation. We examined the effect of rTMS and tDCS, and the added value of neuronavigation in the treatment of MDD.
UNASSIGNED: A search on PubMed, Embase, and Cochrane databases for rTMS or tDCS randomized controlled trials of MDD up to 1 February 2023, yielded 89 studies. We then performed meta-analyses comparing tDCS efficacy to non-neuronavigated rTMS, tDCS to neuronavigated rTMS, and neuronavigated rTMS to non-neuronavigated rTMS. We assessed the significance of the effect in subgroups and in the whole meta-analysis with a z-test and subgroup differences with a chi-square test.
UNASSIGNED: We found small-to-medium effects of both tDCS and rTMS on MDD, with a slightly greater effect from rTMS. No significant difference was found between neuronavigation and non-neuronavigation.
UNASSIGNED: Although both tDCS and rTMS are effective in treating MDD, many patients do not respond. Additionally, current neuronavigation methods are not significantly improving MDD treatment. It is therefore imperative to seek personalized methods for these interventions.

The use of methamphetamine in the United States is increasing, contributing now to the \"fourth wave\" in the national opioid epidemic crisis. People who suffer from methamphetamine use disorder (MUD) have a higher risk of death. No pharmacological interventions are approved by the FDA and psychosocial interventions are only moderately effective. Transcranial Magnetic Stimulation (TMS) is a relatively novel FDA-cleared intervention for the treatment of Major Depressive Disorder (MDD) and other neuropsychiatric conditions. Several lines of research suggest that TMS could be useful for the treatment of addictive disorders, including MUD. We will review those published clinical trials that show potential effects on craving reduction of TMS when applied over the dorsolateral prefrontal cortex (DLPFC) also highlighting some limitations that affect their generalizability and applicability. We propose the use of the Koob and Volkow\'s neurocircuitry model of addiction as a frame to explain the brain effects of TMS in patients with MUD. We will finally discuss new venues that could lead to a more individualized and effective treatment of this complex disorder including the use of neuroimaging, the exploration of different areas of the brain such as the frontopolar cortex or the salience network and the use of biomarkers.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.

BACKGROUND: Binge eating disorder (BED) is the most common eating disorder among those contributing to the development of obesity, and thus acts as a significant burden on the lives and health of patients. It is characterized by complex neurobiology, which includes changes in brain activity and neurotransmitter secretion. Existing treatments are moderately effective, and so the search for new therapies that are effective and safe is ongoing.
OBJECTIVE: This review examines the use of transcranial direct current stimulation (tDCS) in the treatment of binge eating disorder. Searches were conducted on the PubMed/Medline, Research Gate, and Cochrane databases.
RESULTS: Six studies were found that matched the review topic. All of them used the anodal stimulation of the right dorsolateral prefrontal cortex (DLPFC) in BED patients. tDCS proved effective in reducing food cravings, the desire to binge eat, the number of binging episodes, and food intake. It also improved the outcomes of inhibitory control and the treatment of eating disorder psychopathology. The potential mechanisms of action of tDCS in BED are explained, limitations in current research are outlined, and recommendations for future research are provided.
CONCLUSIONS: Preliminary evidence suggests that the anodal application of tDCS to the right DLPFC reduces the symptoms of BED. However, caution should be exercised in the broader use of tDCS in this context due to the small number of studies performed and the small number of patients included. Future studies should incorporate neuroimaging and neurophysiological measurements to elucidate the potential mechanisms of action of tDCS in BED.

This study aimed to evaluate the association of the six parameters, namely stimulation intensity, stimulation frequency, pulses per session, treatment duration, number of sessions, and total number of pulses with the efficacy of conventional transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex for patients with treatment-resistant depression (TRD). A random-effects dose-response meta-analysis of blinded randomized controlled trials (RCTs) involving 2391 participants were conducted to examine the dose-effect relationship of six stimulation parameters. Any of the six parameters significantly individually predicted proportion of variance in efficacy: pulses per session (R²=52.7%), treatment duration (R²=51.2%), total sessions (R²=50.9%), frequency (R²=49.6%), total pulses (R²=49.5%), and intensity (R²= 40.4%). Besides, we identified frequency as a potential parameter interacting with the other five parameters, resulting in a significant increase in variance(ΔR2) ranging from 5.0% to 16.7%. Finally, we found that RCTs using frequency > 10 Hz compared to those of 10 Hz showed better dose-effect relationships. We conclude that the six stimulation parameters significantly predict the dose-effect relationship of conventional rTMS on TRD. Besides, higher stimulation frequency, higher stimulation intensity, and adequate number of pulses were associated with treatment efficacy.

Schizophrenia affects approximately 1% of the population worldwide. Multifactorial reasons, ranging from drug resistance to adverse effects of medications, have necessitated exploring further therapeutic options. Intermittent theta burst stimulation (iTBS) is a novel high-frequency form of transcranial magnetic stimulation, a safe procedure with minor adverse effects with faster and longer-lasting poststimulation effects with a potential role in treating symptoms; however, the exact target brain regions and symptoms are still controversial. Therefore, we aimed to systematically investigate the current literature regarding the therapeutic utilities of iTBS using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Twelve studies were included among which 9 found iTBS effective to some degree. These studies targeted the dorsolateral prefrontal cortex and the midline cerebellum. We performed a random-effects meta-analysis on studies that compared the effects of iTBS on schizophrenia symptoms measured by the Positive and Negative Syndrome Scale (PANSS) to sham treatment. Our results showed no significant difference between iTBS and sham in PANSS positive and negative scores, but a trend-level difference in PANSS general scores ( k = 6, P = 0.07), and a significant difference in PANSS total scores ( k = 6, P = 0.03). Analysis of the studies targeting the dorsolateral prefrontal cortex showed improvement in PANSS negative scores ( k = 5, standardized mean difference = -0.83, P = 0.049), but not in PANSS positive scores. Moderators (intensity, pulse, quality, sessions) did not affect the results. However, considering the small number of studies included in this meta-analysis, future works are required to further explore the effects of these factors and also find optimum target regions for positive symptoms.

The rating of perceived exertion (RPE) is a widely used method for monitoring the load during training, as it provides insight into the subjective intensity of effort experienced during exercises. Considering the role of brain in monitoring and perception of the effort, several studies explored the effect of transcranial direct current stimulation (tDCS) on RPE in different populations. The aim of current study is to review the studies that investigated the effect of tDCS on RPE in three groups including healthy untrained people, physically active persons, and athletes. Nine databases were searched for papers assessing the effect of tDCS on RPE. The data from the included studies were extracted and methodological quality was examined using the risk of bias 2 (ROB2) tool. Thirty-three studies met the inclusion criteria. According to the meta-analysis, active a-tDCS significantly decreased the RPE compared to the sham stimulation. The a-tDCS could decrease the RPE when it was applied over M1 or DLPF. Regarding the measurement tool, Borg\'s scale 6-20 and OMNI scale could show an improvement in RPE scale. A-tDCS is a promising technique that can decrease the RPE. M1 and DLPFC are suggested as the target area of stimulation. From the tools that measure the RPE, Borg\'s RPE 6-20 and OMNI scale could better show the effect of a-tDCS.