A Review of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Combined with Medication and Psychotherapy for Depression.

LEARNING OBJECTIVES: After participating in this CME activity, the psychiatrist should be better able to:• Compare and contrast therapies used in combination with transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) for treating MDD. BACKGROUND: Noninvasive neuromodulation, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has emerged as a major area for treating major depressive disorder (MDD). This review has two primary aims: (1) to review the current literature on combining TMS and tDCS with other therapies, such as psychotherapy and psychopharmacological interventions, and (2) to discuss the efficacy, feasibility, limitations, and future directions of these combined treatments for MDD. METHOD: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched three databases: PubMed, PsycInfo, and Cochrane Library. The last search date was December 5, 2023. RESULTS: The initial search revealed 2,519 records. After screening and full-text review, 58 studies (7 TMS plus psychotherapy, 32 TMS plus medication, 7 tDCS plus psychotherapy, 12 tDCS plus medication) were included. CONCLUSIONS: The current literature on tDCS and TMS paired with psychotherapy provides initial support for integrating mindfulness interventions with both TMS and tDCS. Adding TMS or tDCS to stable doses of ongoing medications can decrease MDD symptoms; however, benzodiazepines may interfere with TMS and tDCS response, and antipsychotics can interfere with TMS response. Pairing citalopram with TMS and sertraline with tDCS can lead to greater MDD symptom reduction compared to using these medications alone. Future studies need to enroll larger samples, include randomized controlled study designs, create more uniform protocols for combined treatment delivery, and explore mechanisms and predictors of change.

An update on noninvasive neuromodulation in the treatment of patients with prolonged disorders of consciousness.

BACKGROUND: With the improvement of emergency techniques, the survival rate of patients with severe brain injury has increased. However, this has also led to an annual increase in the number of patients with prolonged disorders of consciousness (pDoC). Hence, recovery of consciousness is an important part of treatment. With advancing techniques, noninvasive neuromodulation seems a promising intervention. The objective of this review was to summarize the latest techniques and provide the basis for protocols of noninvasive neuromodulations in pDoC. METHODS: This review summarized the advances in noninvasive neuromodulation in the treatment of pDoC in the last 5 years. RESULTS: Variable techniques of neuromodulation are used in pDoC. Transcranial ultrasonic stimulation (TUS) and transcutaneous auricular vagus nerve stimulation (taVNS) are very new techniques, while transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are still the hotspots in pDoC. Median nerve electrical stimulation (MNS) has received little attention in the last 5 years. CONCLUSIONS: Noninvasive neuromodulation is a valuable and promising technique to treat pDoC. Further studies are needed to determine a unified stimulus protocol to achieve optimal effects as well as safety.

Prefrontal tDCS modulates risk-taking in male violent offenders.

Detrimental decision-making is a major problem among violent offenders. Non-invasive brain stimulation offers a promising method to directly influence decision-making and has already been shown to modulate risk-taking in non-violent controls. We hypothesize that anodal transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex beneficially modulates the neural and behavioral correlates of risk-taking in a sample of violent offenders. We expect offenders to show more risky decision-making than non-violent controls and that prefrontal tDCS will induce stronger changes in the offender group. In the current study, 22 male violent offenders and 24 male non-violent controls took part in a randomized double-blind sham-controlled cross-over study applying tDCS over the right dorsolateral prefrontal cortex. Subsequently, participants performed the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging (fMRI). Violent offenders showed significantly less optimal decision-making compared to non-violent controls. Active tDCS increased prefrontal activity and improved decision-making only in violent offenders but not in the control group. Also, in offenders only, prefrontal tDCS influenced functional connectivity between the stimulated area and other brain regions such as the thalamus. These results suggest baseline dependent effects of tDCS and pave the way for treatment options of disadvantageous decision-making behavior in this population.

Clinical usability study of a home-based self-administration transcranial direct current stimulation for primary dysmenorrhea: A randomized controlled trial.

This study tested the usability of a home-based self-administration transcranial direct current stimulation (tDCS) device designed specifically for women's health needs. This is a single center triple blinded clinical usability study for a new wireless, Bluetooth-controlled wearable tDCS device for women's health. The study aims to evaluate the usability and effective blinding of a home-based tDCS system. A total of forty-nine women of reproductive age were randomly allocated (1:1) to receive one session of active tDCS (n = 24) or sham tDCS (n = 25) over the motor and dorsolateral prefrontal cortex. Each participant self-administered one 20-minute session without supervision following guidance on a software application alone. The System Usability Scale (SUS) and the Patient Global Impression of Change (PGIC) were used to evaluate the usability of the system. Regardless of sham or active conditions, all users found the system easy to use without the support of researchers. Usability scores were considered to be "excellent" in both groups and no significant difference was found between sham and active groups showing effective blinding of the device (Active group: 93.7 (83.1-97.5); Sham group 90 (86.2-95) p = 0.79) and PGIC (Active group: 2 (1-2.75); Sham group 2 (1-2) p = 0.99) using an unpaired t-test or non-parametric statistical tests accordingly. The new Bluetooth-controlled wearable tDCS device is easy, safe to use and completely controlled by a smartphone app. This device is focused on women's health and will be tested as an alternative treatment for chronic pelvic pain and mood disturbance associated with menstrual cycles in further research.

Anodal transcranial direct current stimulation enhances response inhibition and attention allocation in fencers.

Background: The aim of this study is to investigate the acute effects of anodal transcranial direct current stimulation (tDCS) on reaction time, response inhibition and attention in fencers. Methods: Sixteen professional female fencers were recruited, and subjected to anodal tDCS and sham stimulation in the primary motor area (M1) one week apart in a randomized, crossover, single-blind design. A two-factor analysis of variance with repeated measures was used to analyze the effects of stimulation conditions (anodal stimulation, sham stimulation) and time (pre-stimulation, post-stimulation) on reaction time, response inhibition, and attention in fencers. Results: The study found a significant improvement in response inhibition and attention allocation from pre-stimulation to post-stimulation following anodal tDCS but not after sham stimulation. There was no statistically significant improvement in reaction time and selective attention. Conclusions: A single session of anodal tDCS could improve response inhibition, attention allocation in female fencers. This shows that tDCS has potential to improve aspects of an athlete's cognitive performance, although we do not know if such improvements would transfer to improved performance in competition. However, more studies involving all genders, large samples, and different sports groups are needed in the future to further validate the effect of tDCS in improving the cognitive performance of athletes.

A Fully Remote Randomized Trial of Transcranial Alternating Current Stimulation for the Acute Treatment of Major Depressive Disorder.

Objective: Major depressive disorder (MDD) is common, but current treatment options have significant limitations in terms of access and efficacy. This study examined the effectiveness of transcranial alternating current stimulation (tACS) for the acute treatment of MDD.Methods: We performed a triple-blind, fully remote, randomized controlled trial comparing tACS with sham treatment. Adults aged 21-65 years meeting DSM 5 criteria for MDD and having a score on the Beck Depression Inventory, Second Edition (BDI-II), between 20 and 63 were eligible to participate. Participants utilized tACS or sham treatment for two 20-minute treatment sessions daily for 4 weeks. The primary outcome was change in BDI-II score from baseline to the week 2 time point in an intent-to treat analysis, followed by analyses of treatment-adherent participants. Secondary analyses examined change at the week 1 and 4 time points, responder rates, subgroup analyses, other self-report mood measures, and safety. The study was conducted from April to October 2022.Results: A total of 255 participants were randomized to active or sham treatment. Improvement in intent-to-treat analysis was not statistically significant at week 2 (P= .056), but there were significant effects in participants with high adherence (P= .005). Significantly greater improvement at week 1 (P= .020) and greater response at week 4 (P= .028) occurred following tACS. Improvements were significantly larger for female participants. There were no significant effects on secondary mood measures. Side effects were minimal and mild.Conclusions: Rapid, clinically significant improvement in depression in adults with MDD was associated with tACS, particularly for women. Compared to other depression therapies, tACS has 3 key advantages: rapid, clinically significant treatment effect, the ability of patients to use the treatment on their own at home, and the rarity and low impact of adverse events.Trial Registration: ClinicalTrials.gov identifier: NCT05384041.

Noninvasive brain stimulation in autism: review and outlook for personalized interventions in adult patients.

Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.

Transcranial direct current stimulation promotes angiogenesis and improves neurological function via the OXA-TF-AKT/ERK signaling pathway in traumatic brain injury.

Traumatic brain injury (TBI) and its resulting complications pose a major challenge to global public health, resulting in increased rates of disability and mortality. Cerebrovascular dysfunction is nearly universal in TBI cases and is closely associated with secondary injury after TBI. Transcranial direct current stimulation (tDCS) shows great potential in the treatment of TBI; however, the exact mechanism remains elusive. In this study, we performed in vivo and in vitro experiments to explore the effects and mechanisms of tDCS in a controlled cortical impact (CCI) rat model simulating TBI. In vivo experiments show that tDCS can effectively reduce brain tissue damage, cerebral edema and neurological deficits. The potential mechanism may be that tDCS improves the neurological function of rats by increasing orexin A (OXA) secretion, upregulating the TF-AKT/ERK signaling pathway, and promoting angiogenesis at the injury site. Cellular experiments showed that OXA promoted HUVEC migration and angiogenesis, and these effects were counteracted by the ERK1/2 inhibitor LY3214996. The results of Matrigel experiment in vivo showed that TNF-a significantly reduced the ability of HUVEC to form blood vessels, but OXA could rescue the effect of TNF-a on the ability of HUVEC to form blood vessels. However, LY3214996 could inhibit the therapeutic effect of OXA. In summary, our preliminary study demonstrates that tDCS can induce angiogenesis through the OXA-TF-AKT/ERK signaling pathway, thereby improving neurological function in rats with TBI.

A Phosphenotron Device for Sensoric Spatial Resolution of Phosphenes within the Visual Field Using Non-Invasive Transcranial Alternating Current Stimulation.

This study presents phosphenotron, a device for enhancing the sensory spatial resolution of phosphenes in the visual field (VF). The phosphenotron employs a non-invasive transcranial alternating current stimulation (NITACS) to modulate brain activity by applying weak electrical currents to the scalp or face. NITACS's unique application induces phosphenes, a phenomenon where light is perceived without external stimuli. Unlike previous invasive methods, NITACS offers a non-invasive approach to create these effects. The study focused on assessing the spatial resolution of NITACS-induced phosphenes, crucial for advancements in visual aid technology and neuroscience. Eight participants were subjected to NITACS using a novel electrode arrangement around the eye orbits. Results showed that NITACS could generate spatially defined phosphene patterns in the VF, varying among individuals but consistently appearing within their VF and remaining stable through multiple stimulations. The study established optimal parameters for vibrant phosphene induction without discomfort and identified electrode positions that altered phosphene locations within different VF regions. Receiver Operating characteristics analysis indicated a specificity of 70.7%, sensitivity of 73.9%, and a control trial accuracy of 98.4%. These findings suggest that NITACS is a promising, reliable method for non-invasive visual perception modulation through phosphene generation.

Computer-aided cognitive training combined with tDCS can improve post-stroke cognitive impairment and cerebral vasomotor function: a randomized controlled trial.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is the focus and difficulty of poststroke rehabilitation intervention with an incidence of up to 61%, which may be related to the deterioration of cerebrovascular function. Computer-aided cognitive training (CACT) can improve cognitive function through scientific training targeting activated brain regions, becoming a popular training method in recent years. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, can regulate the cerebral vascular nerve function, and has an effect on the rehabilitation of cognitive dysfunction after stroke. This study examined the effectiveness of both CACT and tDCS on cognitive and cerebrovascular function after stroke, and explored whether CACT combined with tDCS was more effective. METHODS: A total of 72 patients with PSCI were randomly divided into the conventional cognitive training (CCT) group (n = 18), tDCS group (n = 18), CACT group (n = 18), and CACT combined with tDCS group (n = 18). Patients in each group received corresponding 20-minute treatment 15 times a week for 3 consecutive weeks. Montreal Cognitive Assessment (MoCA) and the Instrumental Activities of Daily Living Scale (IADL) were used to assess patients' cognitive function and the activities of daily living ability. Transcranial Doppler ultrasound (TCD) was used to assess cerebrovascular function, including cerebral blood flow velocity (CBFV), pulse index (PI), and breath holding index (BHI). These outcome measures were measured before and after treatment. RESULTS: Compared with those at baseline, both the MoCA and IADL scores significantly increased after treatment (P < 0.01) in each group. There was no significantly difference in efficacy among CCT, CACT and tDCS groups. The CACT combined with tDCS group showed greater improvement in MoCA scores compared with the other three groups (P < 0.05), especially in the terms of visuospatial and executive. BHI significantly improved only in CACT combined with tDCS group after treatment (p ≤ 0.05) but not in the other groups. Besides, no significant difference in CBFV or PI was found before and after the treatments in all groups. CONCLUSION: Both CACT and tDCS could be used as an alternative to CCT therapy to improve cognitive function and activities of daily living ability after stroke. CACT combined with tDCS may be more effective improving cognitive function and activities of daily living ability in PSCI patients, especially visuospatial and executive abilities, which may be related to improved cerebral vasomotor function reflected by the BHI. TRIAL REGISTRATION NUMBER: The study was registered in the Chinese Registry of Clinical Trials (ChiCTR2100054063). Registration date: 12/08/2021.

Evidence and sources of placebo effects in transcranial direct current stimulation during a single session of visuospatial working memory practice.

Transcranial direct current stimulation (tDCS) can be used to non-invasively augment cognitive training. However, the benefits of tDCS may be due in part to placebo effects, which have not been well-characterized. The purpose of this study was to determine whether tDCS can have a measurable placebo effect on cognitive training and to identify potential sources of this effect. Eighty-three right-handed adults were randomly assigned to one of three groups: control (no exposure to tDCS), sham tDCS, or active tDCS. The sham and active tDCS groups were double-blinded. Each group performed 20 min of an adapted Corsi Block Tapping Task (CBTT), a visuospatial working memory task. Anodal or sham tDCS was applied during CBTT training in a right parietal-left supraorbital montage. After training, active and sham tDCS groups were surveyed on expectations about tDCS efficacy. Linear mixed effects models showed that the tDCS groups (active and sham combined) improved more on the CBTT with training than the control group, suggesting a placebo effect of tDCS. Participants' tDCS expectations were significantly related to the placebo effect, as was the belief of receiving active stimulation. This placebo effect shows that the benefits of tDCS on cognitive training can occur even in absence of active stimulation. Future tDCS studies should consider how treatment expectations may be a source of the placebo effect in tDCS research, and identify ways to potentially leverage them to maximize treatment benefit.

The Application of tDCS to Treat Pain and Psychocognitive Symptoms in Cancer Patients: A Scoping Review.

Background: The use of transcranial direct current stimulation (tDCS) to modulate pain, psychological aspects, and cognitive functions has increased in recent years. The present scoping review aims to investigate the use of tDCS in cancer patients and its significant impact on psychocognitive and pain related symptoms. Methods: From the earliest available date to June 2023, a comprehensive search was conducted in three electronic scientific databases-PubMed, Scopus, and Embase-and other supplementary sources. Ten relevant studies were identified and included, comprising single case studies, randomized controlled trials, pilot studies, and one retrospective study. PRISMA guidelines for scoping reviews were followed. Results: These studies investigated the use of tDCS to improve pain and psychocognitive aspects in patients with various types of cancer, including breast, oral, bladder, lung, pancreatic, head and neck cancer, hepatocellular carcinoma, and meningioma. Overall, the results suggest that tDCS has shown efficacy in relieving pain, reducing anxiety and depression, and improving cognitive function in cancer patients. Conclusion: Due to the limited number and high heterogeneity of the existing literature in this field, more investigation and the establishment of standardized protocols would be required to obtain more conclusive evidence.

Out-of-phase transcranial alternating current stimulation modulates the neurodynamics of inhibitory control.

Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique that enhances cognitive function in a non-invasive manner. Using functional magnetic resonance imaging, we investigated whether tACS with different phase lags (0° and 180°) between the dorsal anterior cingulate and left dorsolateral prefrontal cortices modulated inhibitory control performance during the Stroop task. We found out-of-phase tACS mediated improvements in task performance, which was neurodynamically reflected as putamen, dorsolateral prefrontal, and primary motor cortical activation as well as prefrontal-based top-down functional connectivity. Our observations uncover the neurophysiological bases of tACS-phase-dependent neuromodulation and provide a feasible non-invasive approach to effectively modulate inhibitory control.

Improving SSVEP-BCI Performance Through Repetitive Anodal tDCS-Based Neuromodulation: Insights From Fractal EEG and Brain Functional Connectivity.

This study embarks on a comprehensive investigation of the effectiveness of repetitive transcranial direct current stimulation (tDCS)-based neuromodulation in augmenting steady-state visual evoked potential (SSVEP) brain-computer interfaces (BCIs), alongside exploring pertinent electroencephalography (EEG) biomarkers for assessing brain states and evaluating tDCS efficacy. EEG data were garnered across three distinct task modes (eyes open, eyes closed, and SSVEP stimulation) and two neuromodulation patterns (sham-tDCS and anodal-tDCS). Brain arousal and brain functional connectivity were measured by extracting features of fractal EEG and information flow gain, respectively. Anodal-tDCS led to diminished offsets and enhanced information flow gains, indicating improvements in both brain arousal and brain information transmission capacity. Additionally, anodal-tDCS markedly enhanced SSVEP-BCIs performance as evidenced by increased amplitudes and accuracies, whereas sham-tDCS exhibited lesser efficacy. This study proffers invaluable insights into the application of neuromodulation methods for bolstering BCI performance, and concurrently authenticates two potent electrophysiological markers for multifaceted characterization of brain states.

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.

Effect of transcranial direct current stimulation combined with transcutaneous auricular vagus nerve stimulation on poststroke cognitive impairment: a study protocol for a randomised controlled trial.

INTRODUCTION: Poststroke cognitive impairment is a common complication in stroke survivors, seriously affecting their quality of life. Therefore, it is crucial to improve cognitive function of patients who had a stroke. Transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS) are non-invasive, safe treatments with great potential to improve cognitive function in poststroke patients. However, further improvements are needed in the effectiveness of a single non-invasive brain stimulation technique for cognitive rehabilitation. This study protocol aims to investigate the effect and neural mechanism of the combination of tDCS and taVNS on cognitive function in patients who had a stroke. METHODS AND ANALYSIS: In this single-centre, prospective, parallel, randomised controlled trial, a total of 66 patients with poststroke cognitive impairment will be recruited and randomly assigned (1:1:1) to the tDCS group, the taVNS group and the combination of tDCS and taVNS group. Each group will receive 30 min of treatment daily, five times weekly for 3 weeks. Primary clinical outcome is the Montreal Cognitive Assessment. Secondary clinical outcomes include the Mini-Mental State Examination, Stroop Colour Word Test, Trail Marking Test, Symbol Digit Modalities Test and Modified Barthel Index. All clinical outcomes, functional MRI and diffusion tensor imaging will be measured at preintervention and postintervention. ETHICS AND DISSEMINATION: The trial has been approved by the Ethics Committee of the First Affiliated Hospital of Yangtze University (approval no: KY202390). The results will be submitted for publication in peer-reviewed journals or at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300076632.

Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery: A Randomized Clinical Trial.

Importance: Perioperative anxiety is prevalent among patients undergoing surgical treatment of cancer and often influences their prognosis. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various anxiety-related disorders, but data on the impact of tDCS on perioperative anxiety are limited. Objective: To evaluate the effect of tDCS in reducing perioperative anxiety among patients undergoing laparoscopic colorectal cancer (CRC) resection. Design, Setting, And Participants: This randomized clinical trial was conducted from March to August 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients aged 18 years or older undergoing elective laparoscopic radical resection for CRC were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in September 2023. Interventions: Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex on the afternoon of the day before the operation and in the morning of the day of operation. Main Outcomes and Measures: The main outcome was the incidence of perioperative anxiety from the day of the operation up to 3 days after the procedure, as measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale (range: 0-21, with higher scores indicating more anxiety). Secondary outcomes included postoperative delirium (assessed by the Confusion Assessment Method or Confusion Assessment Method intensive care unit scale); pain (assessed by the 10-point Numeric Rating Scale [NRS], with scores ranging from 0 [no pain] to 10 [worst pain]); frailty (assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of Weight [FRAIL] Index, with scores ranging from 0 [most robust] to 5 [most frail]; and sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], with scores ranging from 0 to 21 and higher scores indicating worse sleep quality) after the 2 sessions of the tDCS intervention. Results: A total of 196 patients (mean [SD] age, 63.5 [11.0] years; 124 [63.3%] men) were recruited and randomly assigned to the active tDCS group (98 patients) or the sham tDCS group (98 patients). After the second tDCS intervention on the day of the operation, the incidence of perioperative anxiety was 38.8% in the active tDCS group and 70.4% in the sham tDCS group (relative risk, 0.55 [95% CI, 0.42-0.73]; P < .001). Patients in the active tDCS group vs the sham tDCS group were less likely to have postoperative delirium (8.2% vs 25.5%) and, at 3 days after the operation, had lower median (IQR) pain scores (NRS, 1.0 [1.0-1.0] vs 2.0 [2.0-2.0]), better median (IQR) sleep quality scores (PSQI, 10.5 [10.0-11.0] vs 12.0 [11.0-13.0]), and lower median (IQR) FRAIL Index (2.0 [1.0-2.0] vs 2.0 [2.0-3.0]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that administration of 2 preoperative sessions of tDCS was associated with a decreased incidence of perioperative anxiety in patients undergoing elective CRC resection. Active tDCS was also associated with better anxiety scores, pain levels, and sleep quality as well as reduced postoperative delirium and frailty. The findings suggest that tDCS may be a novel strategy for improving perioperative anxiety in patients undergoing CRC resection. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2300068859.

Neural correlates of metacognition: Disentangling the brain circuits underlying prospective and retrospective second-order judgments through noninvasive brain stimulation.

Metacognition encompasses the capability to monitor and control one's cognitive processes, with metamemory and metadecision configuring among the most studied higher order functions. Although imaging experiments evaluated the role of disparate brain regions, neural substrates of metacognitive judgments remain undetermined. The aim of this systematic review is to summarize and discuss the available evidence concerning the neural bases of metacognition which has been collected by assessing the effects of noninvasive brain stimulation (NIBS) on human subjects' metacognitive capacities. Based on such literature analysis, our goal is, at first, to verify whether prospective and retrospective second-order judgments are localized within separate brain circuits and, subsequently, to provide compelling clues useful for identifying new targets for future NIBS studies. The search was conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines among PubMed, PsycINFO, PsycARTICLES, PSYNDEX, MEDLINE, and ERIC databases. Overall, 25 studies met the eligibility criteria, yielding a total of 36 experiments employing transcranial magnetic stimulation and 16 ones making use of transcranial electrical stimulation techniques, including transcranial direct current stimulation and transcranial alternating current stimulation. Importantly, we found that both perspective and retrospective judgments about both memory and perceptual decision-making performances depend on the activation of the anterior and lateral portions of the prefrontal cortex, as well as on the activity of more caudal regions such as the premotor cortex and the precuneus. Combining this evidence with results from previous imaging and lesion studies, we advance ventromedial prefrontal cortex as a promising target for future NIBS studies.

Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

Tailoring transcranial alternating current stimulation based on endogenous event-related P3 to modulate premature responses: a feasibility study.

Background: Transcranial alternating current stimulation (tACS) is a brain stimulation method for modulating ongoing endogenous oscillatory activity at specified frequency during sensory and cognitive processes. Given the overlap between event-related potentials (ERPs) and event-related oscillations (EROs), ERPs can be studied as putative biomarkers of the effects of tACS in the brain during cognitive/sensory task performance. Objective: This preliminary study aimed to test the feasibility of individually tailored tACS based on individual P3 (latency and frequency) elicited during a cued premature response task. Thus, tACS frequency was individually tailored to match target-P3 ERO for each participant. Likewise, the target onset in the task was adjusted to match the tACS phase and target-P3 latency. Methods: Twelve healthy volunteers underwent tACS in two separate sessions while performing a premature response task. Target-P3 latency and ERO were calculated in a baseline block during the first session to allow a posterior synchronization between the tACS and the endogenous oscillatory activity. The cue and target-P3 amplitudes, delta/theta ERO, and power spectral density (PSD) were evaluated pre and post-tACS blocks. Results: Target-P3 amplitude significantly increased after activetACS, when compared to sham. Evoked-delta during cue-P3 was decreased after tACS. No effects were found for delta ERO during target-P3 nor for the PSD and behavioral outcomes. Conclusion: The present findings highlight the possible effect of phase synchronization between individualized tACS parameters and endogenous oscillatory activity, which may result in an enhancement of the underlying process (i.e., an increase of target-P3). However, an unsuccessful synchronization between tACS and EEG activity might also result in a decrease in the evoked-delta activity during cue-P3. Further studies are needed to optimize the parameters of endogenous activity and tACS synchronization. The implications of the current results for future studies, including clinical studies, are further discussed since transcranial alternating current stimulation can be individually tailored based on endogenous event-related P3 to modulate responses.