Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex for Phantom Limb Pain.

BACKGROUND: Phantom limb pain (PLP) is a prevalent and distressing occurrence in 60-80% of individuals who have undergone amputations. Recent research underscores the significance of maladaptive cortical plasticity in the genesis of PLP, emphasizing the importance of targeting cortical areas for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive tool for cortical stimulation, demonstrates effectiveness in treating various chronic pain conditions of neuropathic origin. Nevertheless, there exists a limited body of research investigating the application of rTMS as a therapeutic intervention specifically for managing PLP. Notably, the dorsolateral prefrontal cortex (DLPFC) plays a crucial role in central pain processing, suggesting its potential as a key therapeutic target in PLP treatment. There is a lack of adequate data regarding the effectiveness of DLPFC-targeting rTMS in alleviating the pain experienced by PLP patients. OBJECTIVE: In this study, our aim was to investigate the impact of 10 sessions of DLPFC-targeting rTMS on the pain status of individuals experiencing PLP. STUDY DESIGN: Randomized controlled trial. SETTING: Traumatic amputees reporting to the tertiary care center with PLP. METHODS: The study was approved by the Institute Ethics Committee (IECPG-299/27.04.2022) and registered in the Clinical Trials Registry of India (CTRI/2022/07/043938). Nineteen patients suffering from PLP were recruited and randomized into real or sham rTMS groups. In the real rTMS group, patients received 10 sessions of rTMS at the DLPFC contralateral to the amputation site. The rTMS, administered at 90% of the resting motor threshold (RMT), was delivered as 8 trains of 150 pulses per train at the rate of one Hz and an inter-train interval of 60 seconds. The total number of pulses per session was 1,200. The sham group received 10 sessions of sham rTMS through the perpendicular placement of an rTMS coil over the DLPFC. These sessions lasted for the same duration and included the same sounds as the real group but involved no active stimulation. The patients' pain status was evaluated using the Visual Analog Scale (VAS) at baseline, at the end of each session of real or sham rTMS and at the 15th, 30th, and 60th day after the the completion of real or sham therapy. RESULTS: A significant decrease in VAS scores was noted after 10 sessions of real rTMS that targeted the DLPFC, in contrast to the sham rTMS group. The real rTMS group's reduction in VAS scores also persisted during the follow-up. LIMITATIONS: A few patients had to drop out due to physical restrictions and financial constraints. Consequently, only a small number of individuals were able to complete the study protocol successfully. CONCLUSION: A regimen of 10 sessions of real rTMS of the DLPFC was associated with significant pain relief in patients with PLP, and the effects were sustained for 2 months. Therefore, the present study shows that rTMS of the DLPFC has potential as an effective therapeutic intervention for sustained pain relief in PLP patients.

The efficacy of transcranial random noise stimulation in treating tinnitus: a systematic review.

PURPOSE: This review aims to examine the effects of transcranial random noise stimulation (tRNS) on tinnitus and to determine the optimal treatment parameters, if possible. METHODS: A comprehensive search, including MEDLINE, PubMed, EMBASE, CINAHL, SCOPUS, and PEDro, was conducted to determine experiments studying the effects of tRNS on tinnitus from inception to March 1, 2024. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate the quality of the included studies. RESULTS: Seven studies met the eligibility criteria. A total of 616 patients with non-pulsatile tinnitus (mean age 50.93 years; 66% males) were included in this review. The included studies ranged from 3 to 8 out of 10 (median = 7) on the PEDro scale. The results showed that tRNS is an effective intervention in reducing tinnitus symptoms. CONCLUSIONS: The evidence for the effects of tRNS on people with chronic non-pulsatile tinnitus is promising. Administering tRNS with an intensity of 1-2 mA, high-frequency (101-650 Hz), using a 35 cm² electrode size over the auditory cortex and DLPFC, for 20 min with eight sessions may demonstrate the desired tRNS effects. The tRNS stimulation should be contralateral for unilateral tinnitus and bilaterally for bilateral tinnitus. Combining tRNS with other concurrent interventions may show superior effects in reducing tinnitus compared to tRNS alone. Further high-quality studies with larger sample sizes are strongly needed.

Does a single session of transcranial direct current stimulation enhance both physical and psychological performance in national- or international-level athletes? A systematic review.

Some studies showed that a single session of transcranial direct current stimulation (tDCS) has the potential of modulating motor performance in healthy and athletes. To our knowledge, previously published systematic reviews have neither comprehensively investigated the effects of tDCS on athletic performance in both physical and psychological parameters nor investigated the effects of tDCS on high-level athletes. We examined all available research testing a single session of tDCS on strength, endurance, sport-specific performance, emotional states and cognitive performance for better application in competition and pre-competition trainings of national- or international-level athletes. A systematic search was conducted in PubMed, Web of Science, EBSCO, Embase, and Scopus up until to June 2023. Studies were eligible when participants had sports experience at a minimum of state and national level competitions, underwent a single session of tDCS without additional interventions, and received either sham tDCS or no interventions in the control groups. A total of 20 experimental studies (224 participants) were included from 18 articles. The results showed that a single tDCS session improved both physical and psychological parameters in 12 out of the 18 studies. Of these, six refer to the application of tDCS on the motor system (motor cortex, premotor cortex, cerebellum), five on dorsolateral prefrontal cortex and two on temporal cortex. The most sensitive to tDCS are strength, endurance, and emotional states, improved in 67%, 75%, and 75% of studies, respectively. Less than half of the studies showed improvement in sport-specific tasks (40%) and cognitive performance (33%). We suggest that tDCS is an effective tool that can be applied to competition and pre-competition training to improve athletic performance in national- or international-level athletes. Further research would explore various parameters (type of sports, brain regions, stimulation protocol, athlete level, and test tasks) and neural mechanistic studies in improving efficacy of tDCS interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326989, identifier CRD42022326989.

Goal-directed action preparation in humans entails a mixture of corticospinal neural computations.

The seemingly effortless ability of humans to transition from thinking about actions to initiating them relies on sculpting corticospinal output from primary motor cortex. This study tested whether canonical additive and multiplicative neural computations, well-described in sensory systems, generalize to the corticospinal pathway during human action preparation. We used non-invasive brain stimulation to measure corticospinal input-output across varying action preparation contexts during instructed-delay finger response tasks. Goal-directed action preparation was marked by increased multiplicative gain of corticospinal projections to task-relevant muscles and additive suppression of corticospinal projections to non-selected and task-irrelevant muscles. Individuals who modulated corticospinal gain to a greater extent were faster to initiate prepared responses. Our findings provide physiological evidence of combined additive suppression and gain modulation in the human motor system. We propose these computations support action preparation by enhancing the contrast between selected motor representations and surrounding background activity to facilitate response selection and execution.

The cerebellum and the Mirror Neuron System: A matter of inhibition? From neurophysiological evidence to neuromodulatory implications. A narrative review.

Mirror neurons show activity during both the execution (AE) and observation of actions (AO). The Mirror Neuron System (MNS) could be involved during motor imagery (MI) as well. Extensive research suggests that the cerebellum is interconnected with the MNS and may be critically involved in its activities. We gathered evidence on the cerebellum's role in MNS functions, both theoretically and experimentally. Evidence shows that the cerebellum plays a major role during AO and MI and that its lesions impair MNS functions likely because, by modulating the activity of cortical inhibitory interneurons with mirror properties, the cerebellum may contribute to visuomotor matching, which is fundamental for shaping mirror properties. Indeed, the cerebellum may strengthen sensory-motor patterns that minimise the discrepancy between predicted and actual outcome, both during AE and AO. Furthermore, through its connections with the hippocampus, the cerebellum might be involved in internal simulations of motor programs during MI. Finally, as cerebellar neuromodulation might improve its impact on MNS activity, we explored its potential neurophysiological and neurorehabilitation implications.

A dual-brain therapeutic approach using noninvasive brain stimulation based on two-person neuroscience: A perspective review.

Our actions and decisions in everyday life are heavily influenced by social interactions, which are dynamic feedback loops involving actions, reactions, and internal cognitive processes between individual agents. Social interactions induce interpersonal synchrony, which occurs at different biobehavioral levels and comprises behavioral, physiological, and neurological activities. Hyperscanning-a neuroimaging technique that simultaneously measures the activity of multiple brain regions-has provided a powerful second-person neuroscience tool for investigating the phase alignment of neural processes during interactive social behavior. Neural synchronization, revealed by hyperscanning, is a phenomenon called inter-brain synchrony- a process that purportedly facilitates social interactions by prompting appropriate anticipation of and responses to each other's social behaviors during ongoing shared interactions. In this review, I explored the therapeutic dual-brain approach using noninvasive brain stimulation to target inter-brain synchrony based on second-person neuroscience to modulate social interaction. Artificially inducing synchrony between the brains is a potential adjunct technique to physiotherapy, psychotherapy, and pain treatment- which are strongly influenced by the social interaction between the therapist and patient. Dual-brain approaches to personalize stimulation parameters must consider temporal, spatial, and oscillatory factors. Multiple data fusion analysis, the assessment of inter-brain plasticity, a closed-loop system, and a brain-to-brain interface can support personalized stimulation.

Assessment of noninvasive brain stimulation interventions in Parkinson's disease: a systematic review and network meta-analysis.

A network meta-analysis of randomized controlled trials was conducted to compare and rank the effectiveness of various noninvasive brain stimulation (NIBS) for Parkinson's disease (PD). We searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) databases from the date of database inception to April 30th, 2024. Two researchers independently screened studies of NIBS treatment in patients with PD based on inclusion and exclusion criteria. Two researchers independently performed data extraction of the included studies using an Excel spreadsheet and assessed the quality of the literature according to the Cochrane Risk of Bias Assessment Tool (RoB2). Network meta-analysis was performed in StataMP 17.0. A total of 28 studies involving 1628 PD patients were included. The results showed that HF-rTMS over the SMA (SMD = - 2.01; 95% CI [- 2.87, - 1.15]), HF-rTMS over the M1 and DLPFC (SMD = - 1.80; 95% CI [- 2.90, - 0.70]), HF-rTMS over the M1 (SMD = - 1.10; 95% CI [- 1.55, - 0.65]), a-tDCS over the DLPFC (SMD = - 1.08; 95% CI [- 1.90, - 0.27]), HF-rTMS over the M1 and PFC (SMD = - 0.92; 95% CI [- 1.71, - 0.14]), LF-rTMS over the M1 (SMD = - 0.72; 95% CI [- 1.17, - 0.28]), and HF-rTMS over the DLPFC (SMD = - 0.70; 95% CI [- 1.21, - 0.19]) were significantly improved motor function compared with sham stimulation. The SUCRA three highest ranked were HF-rTMS over the SMA (95.1%), HF-rTMS over the M1 and DLPFC (89.6%), and HF-rTMS over the M1 (73.0%). In terms of enhanced cognitive function, HF-rTMS over the DLPFC (SMD = 0.80; 95% CI [0.03,1.56]) was significantly better than sham stimulation. The SUCRA three most highly ranked were a-tDCS over the M1 (69.8%), c-tDCS over the DLPFC (66.9%), and iTBS over the DLPFC (65.3%). HF-rTMS over the M1 (SMD = - 1.43; 95% CI [- 2.26, - 0.61]) and HF-rTMS over the DLPFC (SMD = - 0.79; 95% CI [- 1.45, - 0.12)]) significantly improved depression. The SUCRA three highest ranked were HF-rTMS over the M1 (94.1%), LF-rTMS over the M1 (71.8%), and HF-rTMS over the DLPFC (69.0%). HF-rTMS over the SMA may be the best option for improving motor symptoms in PD patients. a-tDCS and HF-rTMS over the M1 may be the NIBS with the most significant effects on cognition and depression, separately.Trial registration: International Prospective Register of Systematic Review, PROSPERO (CRD42023456088).

Does SLT combined with NIBS enhance naming recovery in post-stroke aphasia? A meta-analysis and systematic review.

BACKGROUND: Non-invasive brain stimulation has been widely used as an adjunctive treatment for aphasia following stroke. OBJECTIVE: The aim of this study was to investigate the effect of non-invasive brain stimulation as an adjunctive treatment on naming function in aphasia following stroke. METHODS: This review included randomized controlled trials (RCTs) involving 5 databases (Web of Science, Embase, Cochrane Library, OVID and PubMed) that investigated the effects of electrical stimulation on stroke patients. The search included literature published up to November 2023. RESULTS: We identified 18 studies, and the standardized mean differences (SMDs) showed that the effect sizes of TMS and tDCS were small to medium. Moreover, the treatment effects persisted over time, indicating long-term efficacy. CONCLUSION: This study suggested that NIBS combined with speech and language therapy can effectively promote the recovery of naming function in patients with post-stroke aphasia (PSA) and that the effects are long lasting.

Use of transcranial magnetic stimulation (TMS) for studying cognitive control in depressed patients: A systematic review.

Major depressive disorder (MDD) is a debilitating mental disorder and the leading cause of disease burden. Major depressive disorder is associated with emotional impairment and cognitive deficit. Cognitive control, which is the ability to use perceptions, knowledge, and information about goals and motivations to shape the selection of goal-directed actions or thoughts, is a primary function of the prefrontal cortex (PFC). Psychotropic medications are one of the main treatments for MDD, but they are not effective for all patients. An alternative treatment is transcranial magnetic stimulation (TMS). Previous studies have provided mixed results on the cognitive-enhancing effects of TMS treatment in patients with MDD. Some studies have found significant improvement, while others have not. There is a lack of understanding of the specific effects of different TMS protocols and stimulation parameters on cognitive control in MDD. Thus, this review aims to synthesize the effectiveness of the TMS methods and a qualitative assessment of their potential benefits in improving cognitive functioning in patients with MDD. We reviewed 21 studies in which participants underwent a treatment of any transcranial magnetic stimulation protocol, such as repetitive TMS or theta-burst stimulation. One of the primary outcome measures was any change in the cognitive control process. Overall, the findings indicate that transcranial magnetic stimulation (TMS) may enhance cognitive function in patients with MDD. Most of the reviewed studies supported the notion of cognitive improvement following TMS treatment. Notably, improvements were predominantly observed in inhibition, attention, set shifting/flexibility, and memory domains. However, fewer significant improvements were detected in evaluations of visuospatial function and recognition, executive function, phonemic fluency, and speed of information processing. This review found evidence supporting the use of TMS as a treatment for cognitive deficits in patients with MDD. The results are promising, but further research is needed to clarify the specific TMS protocol and stimulation locations that are most effective.

Effects of Combining Transcranial Direct Current Stimulation With Balance Training on Anticipatory Postural Adjustments in Persons With Chronic Ankle Instability.

BACKGROUND: The combination of transcranial direct current stimulation (tDCS) with balance training could integrate central and peripheral neural mechanisms. This study aimed to investigate the effects of concurrent balance training and tDCS over the supplementary motor area (SMA) on anticipatory postural adjustments during gait initiation (GI) in persons with chronic ankle instability (CAI). HYPOTHESIS: Balance training will increase the center of pressure (COP) velocity and displacement during GI phases in all participants, and those receiving real tDCS will show greater increases. STUDY DESIGN: Randomized controlled trial. LEVEL OF EVIDENCE: Level 2. METHODS: A total of 32 subjects were allocated to 2 groups: (1) intervention (balance training plus real tDCS) and (2) control (balance training plus sham tDCS). Outcome measures were COP-related parameters (displacement and velocity) during phases of GI (anticipatory, weight transition, and locomotor). RESULTS: The results showed that, in the anticipatory phase, the anteroposterior displacement of the COP was increased significantly at posttest relative to pretest across both groups, F(1,30) = 5.733, P = 0.02. In addition, both groups revealed an increase in the mediolateral COP velocity at posttest, F(1,30) = 10.523, P < 0.01. In the weight transition phase, both groups had higher mediolateral COP velocity at posttest, F(1,30) = 30.636, P < 0.01. In the locomotor phase, in both groups, the anteroposterior COP velocity was increased significantly at posttest compared with pretest, F(1,30) = 5.883, P = 0.02. CONCLUSION: Both groups demonstrated improvements in the anticipatory and execution phases of GI. Since no between-group difference was found, it can be interpreted that the anodal tDCS applied over the SMA has no added value over sham stimulation. CLINICAL RELEVANCE: Balance training is beneficial for persons with CAI and can improve the anticipation and execution phases of GI without the aid of brain stimulation.

Probing Our Built-in Calculator: A Systematic Narrative Review of Noninvasive Brain Stimulation Studies on Arithmetic Operation-Related Brain Areas.

This systematic review presented a comprehensive survey of studies that applied transcranial magnetic stimulation and transcranial electrical stimulation to parietal and nonparietal areas to examine the neural basis of symbolic arithmetic processing. All findings were compiled with regard to the three assumptions of the triple-code model (TCM) of number processing. Thirty-seven eligible manuscripts were identified for review (33 with healthy participants and 4 with patients). Their results are broadly consistent with the first assumption of the TCM that intraparietal sulcus both hold a magnitude code and engage in operations requiring numerical manipulations such as subtraction. However, largely heterogeneous results conflicted with the second assumption of the TCM that the left angular gyrus subserves arithmetic fact retrieval, such as the retrieval of rote-learned multiplication results. Support is also limited for the third assumption of the TCM, namely, that the posterior superior parietal lobule engages in spatial operations on the mental number line. Furthermore, results from the stimulation of brain areas outside of those postulated by the TCM show that the bilateral supramarginal gyrus is involved in online calculation and retrieval, the left temporal cortex in retrieval, and the bilateral dorsolateral prefrontal cortex and cerebellum in online calculation of cognitively demanding arithmetic problems. The overall results indicate that multiple cortical areas subserve arithmetic skills.

Pharmacotherapy and noninvasive neurostimulation for neuropathic pain.

Neuropathic pain poses a significant challenge due to its complex mechanisms, necessitating specific treatments. In recent decades, significant progress has been made in the clinical research of neuropathic pain, marking a shift from empirical strategies to evidence-based medicine in its management. This review outlines both pharmacological and non-pharmacological interventions. Antidepressants (tricyclic and serotonin-noradrenaline reuptake inhibitors), antiepileptics (gabapentin, pregabalin), and topical agents constitute the main pharmacological treatments. These approaches target peripheral or central mechanisms associated with neuropathic pain. Noninvasive neurostimulation, including transcutaneous electrical nerve stimulation (TENS) and repetitive transcranial magnetic stimulation (rTMS), provides non-pharmacological alternatives. However, challenges persist in effectively targeting existing medications and developing drugs that act on novel targets, necessitating innovative therapeutic strategies.

Predicting interindividual response to theta burst stimulation in the lower limb motor cortex using machine learning.

Using theta burst stimulation (TBS) to induce neural plasticity has played an important role in improving the treatment of neurological disorders. However, the variability of TBS-induced synaptic plasticity in the primary motor cortex prevents its clinical application. Thus, factors associated with this variability should be explored to enable the creation of a predictive model. Statistical approaches, such as regression analysis, have been used to predict the effects of TBS. Machine learning may potentially uncover previously unexplored predictive factors due to its increased capacity for capturing nonlinear changes. In this study, we used our prior dataset (Katagiri et al., 2020) to determine the factors that predict variability in TBS-induced synaptic plasticity in the lower limb motor cortex for both intermittent (iTBS) and continuous (cTBS) TBS using machine learning. Validation of the created model showed an area under the curve (AUC) of 0.85 and 0.69 and positive predictive values of 77.7 and 70.0% for iTBS and cTBS, respectively; the negative predictive value was 75.5% for both patterns. Additionally, the accuracy was 0.76 and 0.72, precision was 0.82 and 0.67, recall was 0.82 and 0.67, and F1 scores were 0.82 and 0.67 for iTBS and cTBS, respectively. The most important predictor of iTBS was the motor evoked potential amplitude, whereas it was the intracortical facilitation for cTBS. Our results provide additional insights into the prediction of the effects of TBS variability according to baseline neurophysiological factors.

Repetitive transcranial magnetic stimulation for Alzheimer's disease: an overview of systematic reviews and meta-analysis.

Objective: Alzheimer's disease (AD) is a prevalent neurodegenerative condition that significantly impacts both individuals and society. This study aims to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a treatment for AD by summarizing the evidence from systematic reviews (SRs) and meta-analyses (MAs). Methods: SRs/MAs of rTMS for AD were collected by searching Embase, Web of Science, Cochrane Library, PubMed, CNKI, VIP, Sino-Med, and Wanfang databases. The search was conducted from database creation to January 23, 2024. Methodological quality, reporting quality and risk of bias were assessed using the Assessing Methodological Quality of Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Systematic Reviews (ROBIS) tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In addition, the quality of evidence for outcome measures was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Eight SRs/MAs included in this study met the inclusion criteria. Based on the AMSTAR-2, 4 of the SRs/MA were classified as low quality, while the remaining 4 were deemed to be of very low quality. The PRISMA analysis revealed that out of the 27 items reporting, 16 achieved full reporting (100%). However, there were still some deficiencies in reporting, particularly related to protocol and registration, search strategy, risk of bias, and additional analysis. The ROBIS tool indicated that only 3 SRs/MAs had a low risk of bias. The GRADE assessment indicated that 6 outcomes were of moderate quality (18.75%), 16 were of low quality (50%), and 10 were classified as very low quality (31.25%). Conclusion: Based on the evidence collected, rTMS appears to be effective in improving cognitive function in AD patients, although the methodological quality of the SRs/MAs reduces the reliability of the conclusions and the overall quality is low. However, based on the available results, we still support the value of rTMS as an intervention to improve cognitive function in AD. In future studies, it is necessary to confirm the efficacy of rTMS in AD patients and provide more reliable and scientific data to contribute to evidence-based medicine.

Action video games and posterior parietal cortex neuromodulation enhance both attention and reading in adults with developmental dyslexia.

The impact of action video games on reading performance has been already demonstrated in individuals with and without neurodevelopmental disorders. The combination of action video games and posterior parietal cortex neuromodulation by a transcranial random noise stimulation could enhance brain plasticity, improving attentional control and reading skills also in adults with developmental dyslexia. In a double blind randomized controlled trial, 20 young adult nonaction video game players with developmental dyslexia were trained for 15 h with action video games. Half of the participants were stimulated with bilateral transcranial random noise stimulation on the posterior parietal cortex during the action video game training, whereas the others were in the placebo (i.e. sham) condition. Word text reading, pseudowords decoding, and temporal attention (attentional blink), as well as electroencephalographic activity during the attentional blink, were measured before and after the training. The action video game + transcranial random noise stimulation group showed temporal attention, word text reading, and pseudoword decoding enhancements and P300 amplitude brain potential changes. The enhancement in temporal attention performance was related with the efficiency in pseudoword decoding improvement. Our results demonstrate that the combination of action video game training with parietal neuromodulation increases the efficiency of visual attention deployment, probably reshaping goal-directed and stimulus-driven fronto-parietal attentional networks interplay in young adults with neurodevelopmental conditions.

Use of noninvasive brain stimulation and neurorehabilitation devices to enhance poststroke recovery: review of the current evidence and pitfalls.

Neurorehabilitation devices and technologies are crucial for enhancing stroke recovery. These include noninvasive brain stimulation devices that provide repetitive transcranial magnetic stimulation or transcranial direct current stimulation, which can remodulate an injured brain. Technologies such as robotics, virtual reality, and telerehabilitation are suitable add-ons or complements to physical therapy. However, the appropriate application of these devices and technologies, which target specific deficits and stages, for stroke therapy must be clarified. Accordingly, a literature review was conducted to evaluate the theoretical and practical evidence on the use of neurorehabilitation devices and technologies for stroke therapy. This narrative review provides a practical guide for the use of neurorehabilitation devices and describes the implications of use and potential integration of these devices into healthcare.

Effects of Transcranial Direct Current Stimulation on Cognitive Function in Older Adults with and without Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Noninvasive brain stimulation (NIBS) has shown benefits for cognitive function in older adults. However, the effects of transcranial direct current stimulation (tDCS) on cognitive function in older adults are inconsistent across studies, and the evidence for tDCS has limitations. We aim to explore whether tDCS can improve cognitive function and different cognitive domains (i.e., learning and memory and executive function) in adults aged 65 years and older with and without mild cognitive impairment and to further analyze the influencing factors of tDCS. METHODS: Five English databases (PubMed, Cochrane Library, EMBASE, Web of Science, the cumulative Index to Nursing and Allied Health Literature [CINAHL]) and four Chinese databases were searched from inception to October 14, 2023. Literature screening, data extraction, and quality assessment were completed independently by two reviewers. All statistical analyses were conducted using RevMan software (version 5.3). Standardized mean difference (SMD) along with a 95% confidence interval (CI) was used to express the effect size of the outcomes, and a random-effect model was also used. RESULTS: A total of 10 RCTs and 1,761 participants were included in the meta-analysis, and the risk of bias in those studies was relatively low. A significant effect favoring tDCS on immediate postintervention cognitive function (SMD = 0.16, Z = 2.36, p = 0.02) was found. However, the effects on immediate postintervention learning and memory (SMD = 0.20, Z = 2.00, p = 0.05) and executive function (SMD = 0.10, Z = 1.22, p = 0.22), and 1-month postintervention cognitive function (SMD = 0.12, Z = 1.50, p = 0.13), learning and memory (SMD = 0.17, Z = 1.39, p = 0.16), and executive function (SMD = 0.08, Z = 0.67, p = 0.51) were not statistically significant. CONCLUSION: tDCS can significantly improve the immediate postintervention cognitive function of healthy older adults and MCI elderly individuals. Additional longitudinal extensive sample studies are required to clarify the specific effects of tDCS on different cognitive domains, and the optimal tDCS parameters need to be explored to guide clinical practice.

Comparative efficacy of different noninvasive brain stimulation protocols on upper-extremity motor function and activities of daily living after stroke: a systematic review and network meta-analysis.

The objectives of the study were to systematically evaluate the rehabilitation effect of noninvasive brain stimulation (NIBS) on upper extremity motor function and activities of daily living in stroke patients and to prioritize various stimulation protocols for reliable evidence-based medical recommendations in patients with upper extremity motor dysfunction after stroke. Web of Science, PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and CBM were searched to collect all randomized controlled trials (RCTs) of NIBS to improve upper extremity motor function in stroke patients. The retrieval time was from the establishment of all databases to May 2023. According to the Cochrane system evaluation manual, the quality of the included studies was evaluated, and the data were extracted. Statistical analysis was carried out by using RevMan 5.3, R 4.3.0, and Stata 17.0 software. Finally, 94 RCTs were included, with a total of 5546 patients. Meta-analysis showed that NIBS improved the Fugl-Meyer assessment (FMA) score (mean difference (MD) = 6.51, 95% CI 6.20 ~ 6.82, P < 0.05), MBI score (MD = 7.69, 95% CI 6.57 ~ 8.81, P < 0.05), ARAT score (MD = 5.06, 95% CI 3.85 ~ 6.27, P < 0.05), and motor evoked potential (MEP) amplitude. The modified Ashworth scale score (MD = - 0.37, 95% CI - 0.60 to - 0.14, P < 0.05), National Institutes of Health Stroke Scale score (MD = - 2.17, 95% CI - 3.32 to - 1.11, P < 0.05), incubation period of MEP (MD = - 0.72, 95% CI - 1.06 to - 0.38, P < 0.05), and central motor conduction time (MD = - 0.90, 95% CI - 1.29 to - 0.50, P < 0.05) were decreased in stroke patients. Network meta-analysis showed that the order of interventions in improving FMA scores from high to low was anodal-transcranial direct current stimulation (tDCS) (surface under the cumulative ranking curve (SUCRA) = 83.7%) > cathodal-tDCS (SUCRA = 80.2%) > high-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (SUCRA = 68.5%) > low-frequency (LF)-rTMS (SUCRA = 66.5%) > continuous theta burst stimulation (cTBS) (SUCRA = 54.2%) > bilateral-tDCS (SUCRA = 45.2%) > intermittent theta burst stimulation (iTBS) (SUCRA = 34.1%) > sham-NIBS (SUCRA = 16.0%) > CR (SUCRA = 1.6%). In terms of improving MBI scores, the order from high to low was anodal-tDCS (SUCRA = 88.7%) > cathodal-tDCS (SUCRA = 85.4%) > HF-rTMS (SUCRA = 63.4%) > bilateral-tDCS (SUCRA = 56.0%) > LF-rTMS (SUCRA = 54.2%) > iTBS (SUCRA = 32.4%) > sham-NIBS (SUCRA = 13.8%) > CR (SUCRA = 6.1%). NIBS can effectively improve upper extremity motor function and activities of daily living after stroke. Among the various NIBS protocols, anodal-tDCS demonstrated the most significant intervention effect, followed by cathodal-tDCS and HF-rTMS.

Differences in scalp-to-cortex tissues across age groups, sexes and brain regions: Implications for neuroimaging and brain stimulation techniques.

Aging affects the scalp-to-cortex distance (SCD) and the comprising tissues. This is crucial for noninvasive neuroimaging and brain stimulation modalities as they rely on traversing from the scalp to the cortex or vice versa. The specific relationship between aging and these tissues has not been comprehensively investigated. We conducted a study on 250 younger and older adults to examine age-related differences in SCD and its constituent tissues. We identified region-specific differences in tissue thicknesses related to age and sex. Older adults exhibit larger SCD in the frontocentral regions compared to younger adults. Men exhibit greater SCD in the inferior scalp regions, while women show similar-to-greater SCD values in regions closer to the vertex compared to men. Younger adults and men have thicker soft tissue layers, whereas women and older adults exhibit thicker compact bone layers. CSF is considerably thicker in older adults, particularly in men. These findings emphasize the need to consider age, sex, and regional differences when interpreting SCD and its implications for noninvasive neuroimaging and brain stimulation.

Noninvasive intervention by transcranial ultrasound stimulation: Modulation of neural circuits and its clinical perspectives.

Low-intensity focused transcranial ultrasound stimulation (TUS) is an emerging noninvasive technique capable of stimulating both the cerebral cortex and deep brain structures with high spatial precision. This method is recognized for its potential to comprehensively perturb various brain regions, enabling the modulation of neural circuits, in a manner not achievable through conventional magnetic or electrical brain stimulation techniques. The underlying mechanisms of neuromodulation are based on a phenomenon where mechanical waves of ultrasound kinetically interact with neurons, specifically affecting neuronal membranes and mechanosensitive channels. This interaction induces alterations in the excitability of neurons within the stimulated region. In this review, we briefly present the fundamental principles of ultrasound physics and the physiological mechanisms of TUS neuromodulation. We explain the experimental apparatus and procedures for TUS in humans. Due to the focality, the integration of various methods, including magnetic resonance imaging and magnetic resonance-guided neuronavigation systems, is important to perform TUS experiments for precise targeting. We then review the current state of the literature on TUS neuromodulation, with a particular focus on human subjects, targeting both the cerebral cortex and deep subcortical structures. Finally, we outline future perspectives of TUS in clinical applications in psychiatric and neurological fields.