Towards optimized methodological parameters for maximizing the behavioral effects of transcranial direct current stimulation.

Introduction: Transcranial direct current stimulation (tDCS) administers low-intensity direct current electrical stimulation to brain regions via electrodes arranged on the surface of the scalp. The core promise of tDCS is its ability to modulate brain activity and affect performance on diverse cognitive functions (affording causal inferences regarding regional brain activity and behavior), but the optimal methodological parameters for maximizing behavioral effects remain to be elucidated. Here we sought to examine the effects of 10 stimulation and experimental design factors across a series of five cognitive domains: motor performance, visual search, working memory, vigilance, and response inhibition. The objective was to identify a set of optimal parameter settings that consistently and reliably maximized the behavioral effects of tDCS within each cognitive domain. Methods: We surveyed tDCS effects on these various cognitive functions in healthy young adults, ultimately resulting in 721 effects across 106 published reports. Hierarchical Bayesian meta-regression models were fit to characterize how (and to what extent) these design parameters differentially predict the likelihood of positive/negative behavioral outcomes. Results: Consistent with many previous meta-analyses of tDCS effects, extensive variability was observed across tasks and measured outcomes. Consequently, most design parameters did not confer consistent advantages or disadvantages to behavioral effects-a domain-general model suggested an advantage to using within-subjects designs (versus between-subjects) and the tendency for cathodal stimulation (relative to anodal stimulation) to produce reduced behavioral effects, but these associations were scarcely-evident in domain-specific models. Discussion: These findings highlight the urgent need for tDCS studies to more systematically probe the effects of these parameters on behavior to fulfill the promise of identifying causal links between brain function and cognition.

Transcranial temporal interference stimulation (tTIS) influences event-related alpha activity during mental rotation.

Non-invasive brain stimulation techniques offer therapeutic potential for neurological and psychiatric disorders. However, current methods are often limited in their stimulation depth. The novel transcranial temporal interference stimulation (tTIS) aims to overcome this limitation by non-invasively targeting deeper brain regions. In this study, we aimed to evaluate the efficacy of tTIS in modulating alpha activity during a mental rotation task. The effects of tTIS were compared with transcranial alternating current stimulation (tACS) and a sham control. Participants were randomly assigned to a tTIS, tACS, or sham group. They performed alternating blocks of resting and mental rotation tasks before, during, and after stimulation. During the stimulation blocks, participants received 20 min of stimulation adjusted to their individual alpha frequency (IAF). We assessed shifts in resting state alpha power, event-related desynchronization (ERD) of alpha activity during mental rotation, as well as resulting improvements in behavioral performance. Our results indicate tTIS and tACS to be effective in modulating cortical alpha activity during mental rotation, leading to an increase in ERD from pre- to poststimulation as well as compared to sham stimulation. However, this increase in ERD was not correlated with enhanced mental rotation performance, and resting state alpha power remained unchanged. Our findings underscore the complex nature of tTIS and tACS efficacy, indicating that stimulation effects are more observable during active cognitive tasks, while their impacts are less pronounced on resting neuronal systems.

Acute Effect of Transcranial Direct Current Stimulation in Pelvic Floor Muscle Function in Young Healthy Women: Initial Findings of a Randomized Controlled Trial.

INTRODUCTION AND HYPOTHESIS: Transcranial direct current stimulation (tDCS) can enhance muscle function in healthy individuals. However, it is unknown if tDCS associated with pelvic floor muscle training (PFMT) can improve pelvic floor muscle function (PFMF) in healthy women. The aim of this study was to investigate the acute effect of a single session of tDCS in PFMF compared with sham-tDCS in healthy women. METHODS: A double-blind, cross-over, randomized clinical trial was conducted with healthy, nulliparous and sexually active women. PFMF was assessed by bidigital palpation (PERFECT scale) and intravaginal pressure by a manometer (Peritron™). Participants randomly underwent two tDCS sessions (active and sham) 7 days apart. The electrode was positioned equal for both protocols, the anode electrode in the supplementary motor area (M1) and the cathode electrode in the right supraorbital frontal cortex (Fp2). The current was applied for 20 min at 2 mA in active stimulation and for 30 s in sham-tDCS. The tDCS applications were associated with verbal instructions to PFMT in a seated position. After each tDCS session PFMF was reevaluated. RESULTS: Twenty young healthy women (aged 23.4 ± 1.7 years; body mass index 21.7 ± 2.2 kg/m2) were included. No difference was observed in power, endurance, and intravaginal pressure of PFMF (p > 0.05). The number of sustained contractions improved from 3.0 (2.0-3.5) to 4.0 (3.0-5.0) after active-tDCS (p = 0.0004) and was superior to sham-tDCS (p = 0.01). CONCLUSION: The number of sustained contractions of PFM improved immediately after a single active-tDCS session, with a difference compared with the post-intervention result of sham-tDCS in healthy young women.

Effects of high-definition transcranial direct current stimulation combined with inspiratory muscle training for treating respiratory sequelae of long COVID: A case series.

INTRODUCTION: Long COVID occurs when numerous symptoms begin 3 weeks after acute infection and last for 12 months or more. High-definition transcranial direct current stimulation (HD-tDCS) has been tested in patients with COVID-19; however, previous studies did not investigate the HD-tDCS use combined with inspiratory muscle training (IMT) for respiratory sequelae of long COVID. CASE PRESENTATION: Six individuals (four women and two men) aged between 29 and 71 years and presenting with respiratory sequelae of long COVID were included. They were submitted to an intervention that comprised HD-tDCS combined with IMT twice a week for 5 weeks. Lung function and respiratory muscle assessments were performed at baseline and after 5 weeks of intervention. IMPLICATIONS ON PHYSIOTHERAPY PRACTICE: HD-tDCS may enhance the IMT effects by increasing respiratory muscle strength, efficiency, and lung function of individuals with long COVID.

Current state of clinical ultrasound neuromodulation.

Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation.

Neuromodulation with Ultrasound: Hypotheses on the Directionality of Effects and a Community Resource.

Low-intensity Transcranial Ultrasound Stimulation (TUS) is a promising non-invasive technique for deep-brain stimulation and focal neuromodulation. Research with animal models and computational modelling has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first conduct a systematic review of human TUS studies for perturbing neural function and alleviating brain disorders. We then collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on the human TUS study reported outcomes to date (n = 32 studies, 37 experiments). We find that parameters such as the duty cycle show some predictability regarding whether the targeted area's function is likely to be enhanced or suppressed. Given that human TUS sample sizes are exponentially increasing, we recognize that results can stabilize or change as further studies are reported. Therefore, we conclude by establishing an Iowa-Newcastle (inTUS) resource for the systematic reporting of TUS parameters and outcomes to support further hypothesis testing for greater precision in brain stimulation and neuromodulation with TUS.

Optimal dose and type of non-pharmacological treatments to improve cognitive function in people with Alzheimer's disease: a systematic review and network meta-analysis.

OBJECTIVES: To evaluate and rank the effectiveness of specific non-pharmacological treatments (NPTs) in improving the global cognitive function in individuals with Alzheimer's disease (AD) and to examine the dose-response relationship. METHOD: We conducted a systematic search in PubMed, MEDLINE, Embase, PsycINFO, CENTRAL, WOS, and CNKI from their inception to 15 February 2023. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. RESULTS: We included 68 studies involving 5053 participants in this meta-analysis. The treatments with the highest cumulative probabilities for improving global cognitive function were transcranial direct current stimulation (tDCS), followed by physical exercise (PE), and repetitive transcranial magnetic stimulation (rTMS). Additionally, cognitive stimulation (CS), cognitive training CT), multidisciplinary program (MD), and reminiscence treatment (RT) also significantly improve the global cognitive function of people with AD. A non-linear dose-response association was observed for tDCS, PE, rTMS, CS, and CT with global cognitive improvement. Notably, no minimal threshold was identified for the beneficial effects of PE on cognition. The estimated minimal doses for clinically relevant changes in cognition were 33 min per week for tDCS, 330 MET-min per week for PE, and 8000 pulses per week for rTMS. CONCLUSION: tDCS, PE, and rTMS are the better effective NPTs for enhancing global cognitive function in individuals with AD. Properly dosing these treatments can yield significant clinical benefits. Our findings support the clinical utility of low-dose exercise in improving cognition in people with AD.

Simulating tDCS electrode placement to stimulate both M1 and SMA enhances motor performance and modulates cortical excitability depending on current flow direction.

Introduction: The conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1and T2-weighted MRI-based anatomical models, on motor performance and cortical excitability in healthy individuals. Methods: A total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total). Results: Compared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased short-interval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training. Discussion: These results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow.

Temporal gamma tACS and auditory stimulation affect verbal memory in healthy adults.

Research suggests a potential of gamma oscillation entrainment for enhancing memory in Alzheimer's disease and healthy subjects. Gamma entrainment can be accomplished with oscillatory electrical, but also sensory stimulation. However, comparative studies between sensory stimulation and transcranial alternating current stimulation (tACS) effects on memory processes are lacking. This study examined the effects of rhythmic gamma auditory stimulation (rAS) and temporal gamma-tACS on verbal long-term memory (LTM) and working memory (WM) in 74 healthy individuals. Participants were assigned to two groups according to the stimulation techniques (rAS or tACS). Memory was assessed in three experimental blocks, in which each participant was administered with control, 40, and 60 Hz stimulation in counterbalanced order. All interventions were well-tolerated, and participants reported mostly comparable side effects between real stimulation (40 and 60 Hz) and the control condition. LTM immediate and delayed recall remained unaffected by stimulations, while immediate recall intrusions decreased during 60 Hz stimulation. Notably, 40 Hz interventions improved WM compared to control stimulations. These results highlight the potential of 60 and 40 Hz temporal cortex stimulation for reducing immediate LTM recall intrusions and improving WM performance, respectively, probably due to the entrainment of specific gamma oscillations in the auditory cortex. The results also shed light on the comparative effects of these neuromodulation tools on memory functions, and their potential applications for cognitive enhancement and in clinical trials.

Homeostatic metaplasticity induced by the combination of two inhibitory brain stimulation techniques: Continuous theta burst and transcranial static magnetic stimulation.

Aftereffects of non-invasive brain stimulation techniques may be brain state-dependent. Either continuous theta-burst stimulation (cTBS) as transcranial static magnetic field stimulation (tSMS) reduce cortical excitability. Our objective was to explore the aftereffects of tSMS on a M1 previously stimulated with cTBS. The interaction effect of two inhibitory protocols on cortical excitability was tested on healthy volunteers (n = 20), in two different sessions. A first application cTBS was followed by real-tSMS in one session, or sham-tSMS in the other session. When intracortical inhibition was tested with paired-pulse transcranial magnetic stimulation, LICI (ie., long intracortical inhibition) increased, although the unconditioned motor-evoked potential (MEP) remained stable. These effects were observed in the whole sample of participants regardless of the type of static magnetic field stimulation (real or sham) applied after cTBS. Subsequently, we defined a group of good-responders to cTBS (n = 9) on whom the unconditioned MEP amplitude reduced after cTBS and found that application of real-tSMS (subsequent to cTBS) increased the unconditioned MEP. This MEP increase was not found when sham-tSMS followed cTBS. The interaction of tSMS with cTBS seems not to take place at inhibitory cortical interneurons tested by LICI, since LICI was not differently affected after real and sham tSMS. Our results indicate the existence of a process of homeostatic plasticity when tSMS is applied after cTBS. This work suggests that tSMS aftereffects arise at the synaptic level and supports further investigation into tSMS as a useful tool to restore pathological conditions with altered cortical excitability.

Can non-motor outcomes be improved in chronic stroke? A systematic review on the potential role of non-invasive brain stimulation.

BACKGROUND: Non-invasive brain stimulation induces changes in spontaneous neural activity in the cerebral cortex through facilitatory or inhibitory mechanisms, relying on neuromodulation of neural excitability to impact brain plasticity. This systematic review assesses the state-of-the art and existing evidence regarding the effectiveness of NIBS in cognitive recovery among patients with chronic stroke. MATERIALS AND METHODS: We conducted a systematic search, following PRISMA guidelines, for articles published from January 2010 through September 2023. We searched the following databases: PubMed, Embase, Cochrane Database of Systematic Reviews, PEDro, Rehab Data, and Web of Science. RESULTS: Our electronic searches identified 109 papers. We assessed and included 61 studies based on their pertinence and relevance to the topic. After reading the full text of the selected publications and applying predefined inclusion criteria, we excluded 32 articles, leaving 28 articles for our qualitative analysis. We categorized our results into two sections as follows: (1) Cognitive and emotional domains (11 studies), (2) language and speech functions (16 studies). CONCLUSION: Our findings highlight the potential of NIBS, such as tDCS and rTMS, in the cognitive, linguistic, and emotional recovery of post-stroke patients. Although it seems that NIBS may work as a complementary tool to enhance cognitive and communication abilities in patients with stroke -also in the chronic phase- evidence on behavioural outcomes is still poor. Future studies should focus on this important issue to confirm the effectiveness of neuromodulation in chronic neurological diseases. PROSPERO Registration: CRD42023458370.

Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer's Disease.

The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer's Disease (AD) and to testing new drugs, with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments, such as non-invasive stimulation techniques on AD neuropathology and symptoms. Among the different non-invasive brain stimulation approaches, transcranial alternating current stimulation (tACS) is gaining particular attention due to its ability to externally control gamma oscillations. Here, we outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD, applied specifically at 40 Hz frequency, and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials.

The Effects of Transcranial Direct Current Stimulation (tDCS) in HIV Patients-A Review.

Introduction: HIV is a severe and incurable disease that has a devastating impact worldwide. It affects the immune system and negatively affects the nervous system, leading to various cognitive and behavioral problems. Scientists are actively exploring different therapeutic approaches to combat these issues. One promising method is transcranial direct current stimulation (tDCS), a non-invasive technique that stimulates the brain. Methods: This review aims to examine how tDCS can help HIV patients. Searches were conducted in the Pubmed/Medline, Research Gate, and Cochrane databases. Results: The literature search resulted in six articles focusing on the effects of tDCS on cognitive and behavioral measures in people with HIV. In some cases, tDCS showed positive improvements in the measures assessed, improving executive functions, depression, attention, reaction time, psychomotor speed, speed of processing, verbal learning and memory, and cognitive functioning. Furthermore, the stimulation was safe with no severe side effects. However, the included studies were of low quality, had small sample sizes, and did not use any relevant biomarkers that would help to understand the mechanisms of action of tDCS in HIV. Conclusions: tDCS may help patients with HIV; however, due to the limited number of studies and the diversity of protocols used, caution should be exercised when recommending this treatment option in clinical settings. More high-quality research, preferably involving neurophysiological and neuroimaging measurements, is necessary to better understand how tDCS works in individuals with HIV.

Transcranial focused ultrasound to the posterior cingulate cortex modulates default mode network and subjective experience: an fMRI pilot study.

Background: Transcranial focused ultrasound (TFUS) is an emerging neuromodulation tool for temporarily altering brain activity and probing network functioning. The effects of TFUS on the default mode network (DMN) are unknown. Objective: The study examined the effects of transcranial focused ultrasound (TFUS) on the functional connectivity of the default mode network (DMN), specifically by targeting the posterior cingulate cortex (PCC). Additionally, we investigated the subjective effects of TFUS on mood, mindfulness, and self-related processing. Methods: The study employed a randomized, single-blind design involving 30 healthy subjects. Participants were randomly assigned to either the active TFUS group or the sham TFUS group. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted before and after the TFUS application. To measure subjective effects, the Toronto Mindfulness Scale, the Visual Analog Mood Scale, and the Amsterdam Resting State Questionnaire were administered at baseline and 30 min after sonication. The Self Scale and an unstructured interview were also administered 30 min after sonication. Results: The active TFUS group exhibited significant reductions in functional connectivity along the midline of the DMN, while the sham TFUS group showed no changes. The active TFUS group demonstrated increased state mindfulness, reduced Global Vigor, and temporary alterations in the sense of ego, sense of time, and recollection of memories. The sham TFUS group showed an increase in state mindfulness, too, with no other subjective effects. Conclusions: TFUS targeted at the PCC can alter DMN connectivity and cause changes in subjective experience. These findings support the potential of TFUS to serve both as a research tool and as a potential therapeutic intervention.

Transcranial direct current stimulation over medial prefrontal cortex reduced alpha power and functional connectivity during somatic but not semantic self-referential processing.

Past self-report and cognitive-behavioural studies of the effects of transcranial direct current stimulation (tDCS) targeting the medial prefrontal cortex (mPFC) on semantic self-referential processing (SRP) have yielded mixed results. Meanwhile, electroencephalography (EEG) studies show that alpha oscillation (8-12 Hz) may be involved during both semantic and somatic SRP, although the effect of tDCS on alpha-EEG during SRP remains unknown. The current study assessed the EEG and subjective effects of 2 mA tDCS over the mPFC while participants were SRP either on semantic (life roles, e.g., "friend") or somatic (outer body, e.g., "arms") self-referential stimuli compared to resting state and an external attention memory task in 52 young adults. Results showed that whereas mPFC-tDCS did not yield significant changes in participants' mood or experienced attention or pleasantness levels during the SRP task, EEG source analysis indicated, compared to sham stimulation, that tDCS reduced alpha power during somatic but not semantic SRP in the posterior cingulate cortex (PCC), and the frontal, parietal, temporal, and somatosensory cortex, and reduced the functional connectivity between the left inferior parietal lobule and the ventral PCC, but only when mPFC-tDCS was applied at the second while not the first experimental session. Our results suggest that while mPFC-tDCS may be insufficient to alter immediate subjective experience during SRP, mPFC-tDCS may modulate the power and functional connectivity of the brain's alpha oscillations during somatic SRP. Future research directions are discussed.

The cognitive effect of non-invasive brain stimulation combined with cognitive training in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analysis involving NIBS combined with CT have shown controversial results. The aim of this systematic review and meta-analysis was to evaluate short-term and long-term effects of NIBS combined with CT on improving global cognition and other specific cognitive domains in patients with AD and MCI. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases including PubMed, Web of Science, EBSCO, Cochrane Library and Embase were searched up from inception to 20 November 2023. The PEDro scale and the Cochrane's risk of bias assessment were used to evaluate risk of bias and methodological quality of included studies. All statistical analyses were conducted with Review Manager 5.3. RESULTS: We included 15 studies with 685 patients. The PEDro scale was used to assess methodological quality with a mean score of 7.9. The results of meta-analysis showed that NIBS combined with CT was effective on improving global cognition in AD and MCI (SMD = 0.52, 95% CI (0.18, 0.87), p = 0.003), especially for patients accepting repetitive transcranial magnetic stimulation (rTMS) combined with CT (SMD = 0.46, 95% CI (0.14, 0.78), p = 0.005). AD could achieve global cognition improvement from NIBS combined with CT group (SMD = 0.77, 95% CI (0.19, 1.35), p = 0.01). Transcranial direct current stimulation (tDCS) combined with CT could improve language function in AD and MCI (SMD = 0.29, 95% CI (0.03, 0.55), p = 0.03). At evaluation follow-up, rTMS combined with CT exhibited larger therapeutic responses to AD and MCI in global cognition (SMD = 0.55, 95% CI (0.09, 1.02), p = 0.02). AD could achieve global cognition (SMD = 0.40, 95% CI (0.03, 0.77), p = 0.03) and attention/working memory (SMD = 0.72, 95% CI (0.23, 1.20), p = 0.004) improvement after evaluation follow-up from NIBS combined with CT group. CONCLUSIONS: Overall, NIBS combined with CT, particularly rTMS combined with CT, has both short-term and follow-up effects on improving global cognition, mainly in patients with AD. tDCS combined with CT has advantages on improving language function in AD and MCI. Future more studies need evaluate cognitive effects of NIBS combined with CT on other specific cognitive domain in patients with cognitive deterioration.

Non-invasive brain stimulation improves pain in patients with central post-stroke pain: a systematic review and meta-analysis.

BACKGROUND: Central post-stroke pain (CPSP) significantly interferes with the quality of life and psychological well-being of stroke patients. Non-invasive brain stimulation (NIBS) has attracted significant attention as an emerging method for treating patients with CPSP. OBJECTIVE: To compare the clinical efficacy of noninvasive brain stimulation on pain, and psychological status of patients with central post-stroke pain using meta-analysis. METHODS: A computerized search of multiple databases was performed for identification of randomized controlled trials involving NIBS-led treatment of CPSP patients. Two researchers worked independently on literature screening, data extraction, and quality assessment. Research was conducted from inception of the database until October 2023. RevMan 5.0 and Stata 15.0 software were used to conduct statistical analysis. RESULTS: Sixteen papers with 807 patients were finally included. The results showed that NIBS reduced patients' pain intensity [SMD = -0.39, 95% CI (-0.54, -0.24), p < 0.01] and was more effective in short-term CPSP patients. However, the included studies did not show a significant impact on psychological status, particularly depression. Subgroup analysis suggested that the M1 stimulation point was more effective than other stimulation points [SMD = -0.45, 95% CI (-0.65, -0.25), p < 0.001]. Other stimulation modalities also demonstrated favorable outcomes when compared to rTMS [SMD = -0.67, 95% CI (-1.09, -0.25), p < 0.01]. CONCLUSION: NIBS has a positive impact on pain relief in patients with CPSP, but does not enhance patients' psychological well-being in terms of anxiety or depression. Furthermore, large-sample, high-quality, and multi-center RCTs are needed to explore the benefits of different stimulation durations and parameters in patients with CPSP. The current study has been registered with Prospero under the registration number CRD42023468419.

Intervention modalities for brain fog caused by long-COVID: systematic review of the literature.

Individuals suffering from long-COVID can present with "brain fog", which is characterized by a range of cognitive impairments, such as confusion, short-term memory loss, and difficulty concentrating. To date, several potential interventions for brain fog have been considered. Notably, no systematic review has comprehensively discussed the impact of each intervention type on brain fog symptoms. We included studies on adult (aged > 18 years) individuals with proven long- COVID brain-fog symptoms from PubMed, MEDLINE, Central, Scopus, and Embase. A search limit was set for articles published between 01/2020 and 31/12/2023. We excluded studies lacking an objective assessment of brain fog symptoms and patients with preexisting neurological diseases that affected cognition before COVID-19 infection. This review provided relevant information from 17 studies. The rehabilitation studies utilized diverse approaches, leading to a range of outcomes in terms of the effectiveness of the interventions. Six studies described noninvasive brain stimulation, and all showed improvement in cognitive ability. Three studies described hyperbaric oxygen therapy, all of which showed improvements in cognitive assessment tests and brain perfusion. Two studies showed that the use of Palmitoylethanolamide and Luteolin (PEA-LUT) improved cognitive impairment. Noninvasive brain stimulation and hyperbaric oxygen therapy showed promising results in the treatment of brain fog symptoms caused by long-COVID, with improved perfusion and cortical excitability. Furthermore, both rehabilitation strategies and PEA-LUT administration have been associated with improvements in symptoms of brain fog. Future studies should explore combinations of interventions and include longer follow-up periods to assess the long-term effects of these treatments.

Virtual Reality Action Observation and Motor Imagery to Enhance Neuroplastic Capacity in the Human Motor Cortex: A Pilot Double-blind, Randomized Cross-over Trial.

Neuroplasticity is important for learning, development and recovery from injury. Therapies that can upregulate neuroplasticity are therefore of interest across a range of fields. We developed a novel virtual reality action observation and motor imagery (VR-AOMI) intervention and evaluated whether it could enhance the efficacy of mechanisms of neuroplasticity in the human motor cortex of healthy adults. A secondary question was to explore predictors of the change in neuroplasticity following VR-AOMI. A pre-registered, pilot randomized controlled cross-over trial was performed. Twenty right-handed adults (13 females; mean age: 23.0 ± 4.53 years) completed two experimental conditions in separate sessions; VR-AOMI and control. We used intermittent theta burst stimulation (iTBS) to induce long term potentiation-like plasticity in the motor cortex and recorded motor evoked potentials at multiple timepoints as a measure of corticospinal excitability. The VR-AOMI task did not significantly increase the change in MEP amplitude following iTBS when compared to the control task (Group × Timepoint interaction p = 0.17). However, regression analysis identified the change in iTBS response following VR-AOMI was significantly predicted by the baseline iTBS response in the control task. Specifically, participants that did not exhibit the expected increase in MEP amplitude following iTBS in the control condition appear to have greater excitability following iTBS in the VR-AOMI condition (r = -0.72, p < 0.001). Engaging in VR-AOMI might enhance capacity for neuroplasticity in some people who typically do not respond to iTBS. VR-AOMI may prime the brain for enhanced neuroplasticity in this sub-group.