tDCS-enhanced cognitive training improves attention and alters connectivity in control and somatomotor networks: A triple blind study.

BACKGROUND: Executive dysfunction such as inattention or forgetfulness can lead to disruptions in a person's daily functioning and quality of life. OBJECTIVE/HYPOTHESIS: This triple-blinded randomized clinical trial assessed the efficacy of bifrontal (over the forehead) transcranial direct current stimulation (tDCS) concurrent with cognitive training to improve cognitive performance in a healthy sample. METHODS: Fifty-eight participants were randomly assigned to one of three stimulation conditions (2 mA left anode-right cathode, 2 mA right anode-left cathode, or sham), which was administered with cognitive training tasks 3x/week over 12 weeks with assessments at baseline, midpoint (6 weeks), and post-training (12 weeks). We assessed cognitive performance, functional connectivity, and the influence of individual differences in training advancement. RESULTS: Forty participants completed training. We found that at midpoint and post, all groups improved significantly on overall cognitive performance. The left anode group's attention & vigilance score improved significantly at post, but the other two groups did not. Greater attention training advancement predicted attention improvement by post, most notably in the left anode group. Finally, within-network connectivity decreased in the control network and increased in the somatomotor network across all groups. CONCLUSIONS: These results suggest that, given cognitive training, the left anode montage is more effective at improving attention than the right anode montage and sham. Future research may focus on the application of the left anode montage during cognitive training to assess its effectiveness in improving cognition in neuropsychiatric disorders.

Neural response during prefrontal theta burst stimulation: Interleaved TMS-fMRI of full iTBS protocols.

BACKGROUND: Left prefrontal intermittent theta-burst stimulation (iTBS) has emerged as a safe and effective transcranial magnetic stimulation (TMS) treatment protocol in depression. Though network effects after iTBS have been widely studied, the deeper mechanistic understanding of target engagement is still at its beginning. Here, we investigate the feasibility of a novel integrated TMS-fMRI setup and accelerated echo planar imaging protocol to directly observe the immediate effects of full iTBS treatment sessions. OBJECTIVE/HYPOTHESIS: In our effort to explore interleaved iTBS-fMRI feasibility, we hypothesize that TMS will induce acute BOLD signal changes in both the stimulated area and interconnected neural regions. METHODS: Concurrent TMS-fMRI with full sessions of neuronavigated iTBS (i.e. 600 pulses) of the left dorsolateral prefrontal cortex (DLPFC) was investigated in 18 healthy participants. In addition, we conducted four TMS-fMRI sessions in a single patient on long-term maintenance iTBS for bipolar depression to test the transfer to clinical cases. RESULTS: Concurrent TMS-fMRI was feasible for iTBS sequences with 600 pulses. During interleaved iTBS-fMRI, an increase of the BOLD signal was observed in a network including bilateral DLPFC regions. In the clinical case, a reduced BOLD response was found in the left DLPFC and the subgenual anterior cingulate cortex, with high variability across individual sessions. CONCLUSIONS: Full iTBS sessions as applied for the treatment of depressive disorders can be established in the interleaved iTBS-fMRI paradigm. In the future, this experimental approach could be valuable in clinical samples, for demonstrating target engagement by iTBS protocols and investigating their mechanisms of therapeutic action.

Single closed-loop acoustic stimulation targeting memory consolidation suppressed hippocampal ripple and thalamo-cortical spindle activity in mice.

Brain rhythms of sleep reflect neuronal activity underlying sleep-associated memory consolidation. The modulation of brain rhythms, such as the sleep slow oscillation (SO), is used both to investigate neurophysiological mechanisms as well as to measure the impact of sleep on presumed functional correlates. Previously, closed-loop acoustic stimulation in humans targeted to the SO Up-state successfully enhanced the slow oscillation rhythm and phase-dependent spindle activity, although effects on memory retention have varied. Here, we aim to disclose relations between stimulation-induced hippocampo-thalamo-cortical activity and retention performance on a hippocampus-dependent object-place recognition task in mice by applying acoustic stimulation at four estimated SO phases compared to sham condition. Across the 3-h retention interval at the beginning of the light phase closed-loop stimulation failed to improve retention significantly over sham. However, retention during SO Up-state stimulation was significantly higher than for another SO phase. At all SO phases, acoustic stimulation was accompanied by a sharp increase in ripple activity followed by about a second-long suppression of hippocampal sharp wave ripple and longer maintained suppression of thalamo-cortical spindle activity. Importantly, dynamics of SO-coupled hippocampal ripple activity distinguished SOUp-state stimulation. Non-rapid eye movement (NREM) sleep was not impacted by stimulation, yet preREM sleep duration was effected. Results reveal the complex effect of stimulation on the brain dynamics and support the use of closed-loop acoustic stimulation in mice to investigate the inter-regional mechanisms underlying memory consolidation.

Effects of rTMS to primary motor cortex and cerebellum on balance control in healthy adults.

Both the primary motor cortex (M1) and the cerebellum are crucial for postural stability and deemed as potential targets for non-invasive brain stimulation (NIBS) to enhance balance performance. However, the optimal target remains unknown. The purpose of this study was to compare the role of M1 and the cerebellum in modulating balance performance in young healthy adults using facilitatory 5 Hz repetitive transcranial magnetic stimulation (rTMS). Twenty-one healthy young adults (mean age = 27.95 ± 1.15 years) received a single session of 5 Hz rTMS on M1 and the cerebellum in a cross-over order with a 7-day washout period between the two sessions. Three balance assessments were performed on the Biodex Balance system SD: Limits of Stability (LOS), modified Clinical Test of Sensory Interaction on Balance (mCTSIB), and Balance Error Scoring System (BESS). No significant effect of rTMS was found on the LOS. The effect of rTMS on the mCTSIB was mediated by stimulation target, proprioception, and vision (p = .003, ηp 2 = 0.37). Cerebellar rTMS improved the mCTSIB sway index under eyes closed-foam surface condition (p = .02), whereas M1 rTMS did not result in improvement on the mCTSIB. The effect of rTMS on the BESS was mediated by stimulation target, posture, and proprioception (p = .049, ηp 2 = 0.14). Cerebellar rTMS enhanced reactive balance performance during most sensory deprived conditions.

Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review.

Despite the numerous pharmacological interventions targeting dementia, no disease-modifying therapy is available, and the prognosis remains unfavorable. A promising perspective involves tackling high-frequency gamma-band (> 30 Hz) oscillations involved in hippocampal-mediated memory processes, which are impaired from the early stages of typical Alzheimer's Disease (AD). Particularly, the positive effects of gamma-band entrainment on mouse models of AD have prompted researchers to translate such findings into humans using transcranial alternating current stimulation (tACS), a methodology that allows the entrainment of endogenous cortical oscillations in a frequency-specific manner. This systematic review examines the state-of-the-art on the use of gamma-tACS in Mild Cognitive Impairment (MCI) and dementia patients to shed light on its feasibility, therapeutic impact, and clinical effectiveness. A systematic search from two databases yielded 499 records resulting in 10 included studies and a total of 273 patients. The results were arranged in single-session and multi-session protocols. Most of the studies demonstrated cognitive improvement following gamma-tACS, and some studies showed promising effects of gamma-tACS on neuropathological markers, suggesting the feasibility of gamma-tACS in these patients anyhow far from the strong evidence available for mouse models. Nonetheless, the small number of studies and their wide variability in terms of aims, parameters, and measures, make it difficult to draw firm conclusions. We discuss results and methodological limitations of the studies, proposing possible solutions and future avenues to improve research on the effects of gamma-tACS on dementia.

Disentangling Cerebellar and Parietal Contributions to Gait and Body Schema: A Repetitive Transcranial Magnetic Stimulation Study.

The overlap between motor and cognitive signs resulting from posterior parietal cortex (PPC) and cerebellar lesions can mask their relative contribution in the sensorimotor integration process. This study aimed to identify distinguishing motor and cognitive features to disentangle PPC and cerebellar involvement in two sensorimotor-related functions: gait and body schema representation. Thirty healthy volunteers were enrolled and randomly assigned to PPC or cerebellar stimulation. Sham stimulation and 1 Hz-repetitive-Transcranial-Magnetic-Stimulation were delivered over P3 or cerebellum before a balance and a walking distance estimation task. Each trial was repeated with eyes open (EO) and closed (EC). Eight inertial measurement units recorded spatiotemporal and kinematic variables of gait. Instability increased in both groups after real stimulation: PPC inhibition resulted in increased instability in EC conditions, as evidenced by increased ellipse area and range of movement in medio-lateral and anterior-posterior (ROMap) directions. Cerebellar inhibition affected both EC (increased ROMap) and EO stability (greater displacement of the center of mass). Inhibitory stimulation (EC vs. EO) affected also gait spatiotemporal variability, with a high variability of ankle and knee angles plus different patterns in the two groups (cerebellar vs parietal). Lastly, PPC group overestimates distances after real stimulation (EC condition) compared to the cerebellar group. Stability, gait variability, and distance estimation parameters may be useful clinical parameters to disentangle cerebellar and PPC sensorimotor integration deficits. Clinical differential diagnosis efficiency can benefit from this methodological approach.

Investigating Cerebello-Frontal Circuits Associated with Emotional Prosody: A Double-Blind tDCS and fNIRS study.

The emotional and cognitive cerebellum has been explored by several studies in the past years. Recent evidence suggested the possible contribution of the cerebellum in processing emotional prosody, namely the ability to comprehend the emotional content of a given vocal utterance, likely mediated by anatomical and functional cerebello-prefrontal connections. In the present study, the involvement of a functional cerebello-prefrontal network in recognising emotional prosody was assessed by combining non-invasive anodal transcranial direct current stimulation (tDCS) over the right or the left cerebellum and functional Near Infrared Spectroscopy of the prefrontal cortex, in a double-blind within-subject experimental design on healthy participants. The results showed that right and, to a less extent, left cerebellar tDCS (as compared to sham stimulation) reduced neural activation in the prefrontal cortex while accuracy and reaction times at the vocal recognition task remained unchanged. These findings highlight functional properties of the cerebello-frontal connections and the psychophysiological effects of cerebellar brain stimulation, with possible clinical applications in psychiatric and neurological conditions.

Driving innovation in addiction treatment: role of transcranial magnetic stimulation.

Addictions comprises heterogenous psychiatric conditions caused by the complex interaction of genetic, neurobiological, psychological, and environmental factors with a chronic relapsing-remitting pattern. Despite the long-standing efforts of preclinical and clinical research studies, addiction field has seen relatively slow progress when it comes to the development of new therapeutic interventions, most of which failed to demonstrate a significant efficacy. This is likely due to the very complex interplay of many factors that contribute to both the development and expression of addictions. The imbalance between the salience and the reward brain network circuitry has been proposed as the neurobiological mechanisms explaining the pathognomonic symptoms of addictions.Non-invasive neuromodulation techniques have been proposed as a promising therapeutic intervention to restore these brain circuits dysfunctions. Here, we propose a multi-level strategy to innovate the diagnosis and the treatment of addictive disorders.

Neuromodulation of Executive Dysfunction in Patients with Acute Stroke Using Transcranial Direct Current Stimulation: Study Protocol for a Triple-Blind, Randomized Sham-Controlled Trial.

Research on the benefits of non-invasive brain stimulation in stroke patients to improve executive functions is scarce. The objective of this study was to investigate the effectiveness of transcranial direct current stimulation (tDCS) in combination with cognitive training for the rehabilitation of executive functions in acute and subacute stroke patients as well as to explore the underlying physiological mechanisms. A triple-blinded, randomized-controlled clinical trial will be conducted involving 60 stroke patients with frontal or basal ganglia lesions and a Montreal Cognitive Assessment (MoCA) score less than 26. Participants will be randomly assigned to receive active tDCS (anode over the left dorsolateral prefrontal cortex, cathode at the right supraorbital region, 20 min at 2 mA) or sham tDCS in a 1:1 ratio for 10 sessions, followed by targeted executive function training. The primary efficacy outcome will be the MoCA score, while secondary outcomes will include the five-digit test (inhibitory control), the Digit Span Task (working memory), the abbreviated version of the Wisconsin Card Sorting test (cognitive flexibility), modified Rankin scale (functional state), Beck-II depression inventory, apathy evaluation scale, and the WHOQOL-BREF (quality of life), assessed immediately after the intervention and at 1, 3, 6, and 12 months post-intervention. Additionally, resting-state functional connectivity and blood biomarkers, such as neurotrophins, growth factors, and inflammatory molecules, will be evaluated before and after the intervention. This study will contribute to the investigation of the efficacy of tDCS in rehabilitating executive functions in acute and subacute stroke patients. The multidimensional approach utilized in this study, which includes analysis of resting-state connectivity and neuroplasticity-related blood biomarkers, is expected to provide insights into the underlying brain mechanisms involved in the rehabilitation of dysexecutive syndrome.

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.

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.

Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

Aligning Event-Related Potentials with Transcranial Alternating Current Stimulation for Modulation-a Review.

This review aims to demonstrate the connections between event-related potentials (ERPs), event-related oscillations (EROs), and non-invasive brain stimulation (NIBS), with a specific focus on transcranial alternating current stimulation (tACS). We begin with a short examination and discussion of the relation between ERPs and EROs. Then, we investigate the diverse fields of NIBS, highlighting tACS as a potent tool for modulating neural oscillations and influencing cognitive performance. Emphasizing the impact of tACS on individual ERP components, this article offers insights into the potential of conventional tACS for targeted stimulation of single ERP components. Furthermore, we review recent articles that explore a novel approach of tACS: ERP-aligned tACS. This innovative technique exploits the temporal precision of ERP components, aligning tACS with specific neural events to optimize stimulation effects and target the desired neural response. In conclusion, this review combines current knowledge to explore how ERPs, EROs, and NIBS interact, particularly highlighting the modulatory possibilities offered by tACS. The incorporation of ERP-aligned tACS introduces new opportunities for future research, advancing our understanding of the complex connection between neural oscillations and cognitive processes.

Neurocognitive function as outcome and predictor for prefrontal transcranial direct current stimulation in major depressive disorder: an analysis from the DepressionDC trial.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex might beneficially influence neurocognitive dysfunctions associated with major depressive disorder (MDD). However, previous studies of neurocognitive effects of tDCS have been inconclusive. In the current study, we analyzed longitudinal, neurocognitive data from 101 participants of a randomized controlled multicenter trial (DepressionDC), investigating the efficacy of bifrontal tDCS (2 mA, 30 min/d, for 6 weeks) in patients with MDD and insufficient response to selective serotonin reuptake inhibitors (SSRI). We assessed whether active tDCS compared to sham tDCS elicited beneficial effects across the domains of memory span, working memory, selective attention, sustained attention, executive process, and processing speed, assessed with a validated, digital test battery. Additionally, we explored whether baseline cognitive performance, as a proxy of fronto-parietal-network functioning, predicts the antidepressant effects of active tDCS versus sham tDCS. We found no statistically significant group differences in the change of neurocognitive performance between active and sham tDCS. Furthermore, baseline cognitive performance did not predict the clinical response to tDCS. Our findings indicate no advantage in neurocognition due to active tDCS in MDD. Additional research is required to systematically investigate the effects of tDCS protocols on neurocognitive performance in patients with MDD.

The neurophysiological aftereffects of brain stimulation in human primary motor cortex: a Sham-controlled comparison of three protocols.

Paired associative stimulation (PAS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are non-invasive brain stimulation methods that are used to modulate cortical excitability. Whether one technique is superior to the others in achieving this outcome and whether individuals that respond to one intervention are more likely to respond to another remains largely unknown. In the present study, the neurophysiological aftereffects of three excitatory neurostimulation protocols were measured with transcranial magnetic stimulation (TMS). Twenty minutes of PAS at an ISI of 25 ms, anodal tDCS, 20-Hz tACS, and Sham stimulation were administered to 31 healthy adults in a repeated measures design. Compared with Sham, none of the stimulation protocols significantly modulated corticospinal excitability (input/ouput curve and slope, TMS stimulator intensity required to elicit MEPs of 1-mV amplitude) or intracortical excitability (short- and long-interval intracortical inhibition, intracortical facilitation, cortical silent period). Sham-corrected responder analysis estimates showed that an average of 41 (PAS), 39 (tDCS), and 39% (tACS) of participants responded to the interventions with an increase in corticospinal excitability. The present data show that three stimulation protocols believed to increase cortical excitability are associated with highly heterogenous and variable aftereffects that may explain a lack of significant group effects.

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.

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.

TMS and tDCS as potential tools for the treatment of cognitive deficits in Parkinson's disease: a meta-analysis.

BACKGROUND: Cognitive deficits are common nonmotor symptoms in Parkinson's disease (PD). Non-Invasive Brain Stimulation (NIBS) could be a potential aid to prevent or delay dementia progression in this clinical population. However, previous studies reported controversial results concerning their efficacy on cognitive symptoms of PD. Hence, the present meta-analysis aims to systematically examine the effects of NIBS as possible treatments for PD cognitive impairments. Understanding NIBS' impact on these symptoms may be of outstanding importance to implement new therapeutic strategies and improve the patients' quality of life. METHODS: EMBASE, Scopus, and PubMed databases were systematically searched for consecutive studies published from 2000 to March 2023 describing Randomized Controlled Trials studies evaluating the effect of NIBS on PD cognitive symptoms. From the included studies, data concerning neuropsychological tests were extracted and grouped into six cognitive domains, separately analyzed. Hedge's method was computed as the effect size measure of the extracted data; heterogeneity among studies and publication bias were also assessed. The Cochrane's RoB2 tool was used to evaluate the risk of bias for each of the included studies. RESULTS: After database searching and screening of texts, sixteen studies met the inclusion criteria. No significant results emerged from any investigated cognitive domain when comparing NIBS and sham treatments. CONCLUSION: Several factors may have contributed to the lack of effects; among these, methodological choices, the small sample of studies, the high heterogeneity of data and stimulation protocols pose the need for more controlled studies to highlight the potentiality of NIBS as a future treatment for PD cognitive impairments.

Comparative efficacy of non-invasive brain stimulation for post-stroke cognitive impairment: a network meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a burgeoning approach with the potential to significantly enhance cognition and functional abilities in individuals who have undergone a stroke. However, the current evidence lacks robust comparisons and rankings of various NIBS methods concerning the specific stimulation sites and parameters used. To address this knowledge gap, this systematic review and meta-analysis seek to offer conclusive evidence on the efficacy and safety of NIBS in treating post-stroke cognitive impairment. METHODS: A systematic review of randomized control trials (RCT) was performed using Bayesian network meta-analysis. We searched RCT in the following databases until June 2022: Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and EMBASE. We compared any active NIBS to control in terms of improving cognition function and activities of daily living (ADL) capacity following stroke. RESULTS: After reviewing 1577 retrieved citations, a total of 26 RCTs were included. High-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (mean difference 2.25 [95% credible interval 0.77, 3.66]) was identified as a recommended approach for alleviating the global severity of cognition. Dual-rTMS (27.61 [25.66, 29.57]) emerged as a favorable technique for enhancing ADL function. In terms of stimulation targets, the dorsolateral prefrontal cortex exhibited a higher ranking in relation to the global severity of cognition. CONCLUSIONS: Among various NIBS techniques, HF-rTMS stands out as the most promising intervention for enhancing cognitive function. Meanwhile, Dual-rTMS is highly recommended for improving ADL capacity.

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.