The distinct and potentially conflicting effects of tDCS and tRNS on brain connectivity, cortical inhibition, and visuospatial memory.

Noninvasive brain stimulation (NIBS) techniques, including transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS), are emerging as promising tools for enhancing cognitive functions by modulating brain activity and enhancing cognitive functions. Despite their potential, the specific and combined effects of tDCS and tRNS on brain functions, especially regarding functional connectivity, cortical inhibition, and memory performance, are not well-understood. This study aims to explore the distinct and combined impacts of tDCS and tRNS on these neural and cognitive parameters. Using a within-subject design, ten participants underwent four stimulation conditions: sham, tDCS, tRNS, and combined tDCS + tRNS. We assessed the impact on resting-state functional connectivity, cortical inhibition via Cortical Silent Period (CSP), and visuospatial memory performance using the Corsi Block-tapping Test (CBT). Our results indicate that while tDCS appears to induce brain lateralization, tRNS has more generalized and dispersive effects. Interestingly, the combined application of tDCS and tRNS did not amplify these effects but rather suggested a non-synergistic interaction, possibly due to divergent mechanistic pathways, as observed across fMRI, CSP, and CBT measures. These findings illuminate the complex interplay between tDCS and tRNS, highlighting their non-additive effects when used concurrently and underscoring the necessity for further research to optimize their application for cognitive enhancement.

Enhancement of phonemic verbal fluency in multilingual young adults by transcranial random noise stimulation.

Several studies have analyzed the effects of transcranial direct current stimulation on verbal fluency tasks in non-clinical populations. Nevertheless, the reported effects on verbal fluency are inconsistent. In addition, the effect of other techniques such as transcranial random noise stimulation (tRNS) on verbal fluency enhancement has yet to be studied in healthy multilingual populations. This study aims to explore the effects of tRNS on verbal fluency in healthy multilingual individuals. Fifty healthy multilingual (Spanish, English and Basque) adults were randomly assigned to a tRNS or sham group. Electrodes were placed on the left dorsolateral prefrontal cortex and left inferior frontal gyrus. All participants performed phonemic and semantic verbal fluency tasks before, during (online assessment) and immediately after (offline assessment) stimulation in three different languages. The results showed significantly better performance by participants who received tRNS in the phonemic verbal fluency tasks in Spanish (in the online and offline assessment) and English (in the offline assessment). No differences between conditions were found in Basque nor semantic verbal fluency. These findings suggests that tRNS on the left prefrontal cortex could help improve phonemic, yet not semantic, fluency in healthy multilingual adults.

The effects of prefrontal tDCS and hf-tRNS on the processing of positive and negative emotions evoked by video clips in first- and third-person.

The causal role of the cerebral hemispheres in positive and negative emotion processing remains uncertain. The Right Hemisphere Hypothesis proposes right hemispheric superiority for all emotions, while the Valence Hypothesis suggests the left/right hemisphere's primary involvement in positive/negative emotions, respectively. To address this, emotional video clips were presented during dorsolateral prefrontal cortex (DLPFC) electrical stimulation, incorporating a comparison of tDCS and high frequency tRNS stimulation techniques and manipulating perspective-taking (first-person vs third-person Point of View, POV). Four stimulation conditions were applied while participants were asked to rate emotional video valence: anodal/cathodal tDCS to the left/right DLPFC, reverse configuration (anodal/cathodal on the right/left DLPFC), bilateral hf-tRNS, and sham (control condition). Results revealed significant interactions between stimulation setup, emotional valence, and POV, implicating the DLPFC in emotions and perspective-taking. The right hemisphere played a crucial role in both positive and negative valence, supporting the Right Hemisphere Hypothesis. However, the complex interactions between the brain hemispheres and valence also supported the Valence Hypothesis. Both stimulation techniques (tDCS and tRNS) significantly modulated results. These findings support both hypotheses regarding hemispheric involvement in emotions, underscore the utility of video stimuli, and emphasize the importance of perspective-taking in this field, which is often overlooked.

Exploring the Prospects of Transcranial Electrical Stimulation (tES) as a Therapeutic Intervention for Post-Stroke Motor Recovery: A Narrative Review.

INTRODUCTION: Stroke survivors often have motor impairments and related functional deficits. Transcranial Electrical Stimulation (tES) is a rapidly evolving field that offers a wide range of capabilities for modulating brain function, and it is safe and inexpensive. It has the potential for widespread use for post-stroke motor recovery. Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), and Transcranial Random Noise Stimulation (tRNS) are three recognized tES techniques that have gained substantial attention in recent years but have different mechanisms of action. tDCS has been widely used in stroke motor rehabilitation, while applications of tACS and tRNS are very limited. The tDCS protocols could vary significantly, and outcomes are heterogeneous. PURPOSE: the current review attempted to explore the mechanisms underlying commonly employed tES techniques and evaluate their prospective advantages and challenges for their applications in motor recovery after stroke. CONCLUSION: tDCS could depolarize and hyperpolarize the potentials of cortical motor neurons, while tACS and tRNS could target specific brain rhythms and entrain neural networks. Despite the extensive use of tDCS, the complexity of neural networks calls for more sophisticated modifications like tACS and tRNS.

tRNS boosts visual perceptual learning in participants with bilateral macular degeneration.

Perceptual learning (PL) has shown promise in enhancing residual visual functions in patients with age-related macular degeneration (MD), however it requires prolonged training and evidence of generalization to untrained visual functions is limited. Recent studies suggest that combining transcranial random noise stimulation (tRNS) with perceptual learning produces faster and larger visual improvements in participants with normal vision. Thus, this approach might hold the key to improve PL effects in MD. To test this, we trained two groups of MD participants on a contrast detection task with (n = 5) or without (n = 7) concomitant occipital tRNS. The training consisted of a lateral masking paradigm in which the participant had to detect a central low contrast Gabor target. Transfer tasks, including contrast sensitivity, near and far visual acuity, and visual crowding, were measured at pre-, mid and post-tests. Combining tRNS and perceptual learning led to greater improvements in the trained task, evidenced by a larger increment in contrast sensitivity and reduced inhibition at the shortest target to flankers' distance. The overall amount of transfer was similar between the two groups. These results suggest that coupling tRNS and perceptual learning has promising potential applications as a clinical rehabilitation strategy to improve vision in MD patients.

Transcranial random noise stimulation (tRNS) improves hot and cold executive functions in children with attention deficit-hyperactivity disorder (ADHD).

Children with attention deficit-hyperactivity disorder (ADHD) have impaired hot and cold executive functions, which is thought to be related to impaired ventromedial and dorsolateral prefrontal cortex (vmPFC and dlPFC) functions. The present study aimed to assess the impact concurrent stimulation of dlPFC and vmPFC through transcranial random noise stimulation (tRNS), a non-invasive brain stimulation tool which enhances cortical excitability via application of alternating sinusoidal currents with random frequencies and amplitudes over the respective target regions on hot and cold executive functions. Eighteen children with ADHD received real and sham tRNS over the left dlPFC and the right vmPFC in two sessions with one week interval. The participants performed Circle Tracing, Go/No-Go, Wisconsin Card Sorting, and Balloon Analogue Risk Tasks during stimulation in each session. The results showed improved ongoing inhibition, prepotent inhibition, working memory, and decision making, but not set-shifting performance, during real, as compared to sham stimulation. This indicates that simultaneous stimulation of the dlPFC and the vmPFC improves hot and cold executive functions in children with ADHD.

Single sessions of transcranial direct current stimulation and transcranial random noise stimulation exert no effect on sleepiness in patients with narcolepsy and idiopathic hypersomnia.

Background: Hypersomnia poses major challenges to treatment providers given the limitations of available treatment options. In this context, the application of non-invasive brain stimulation techniques such as transcranial electrical stimulation (tES) may open up new avenues to effective treatment. Preliminary evidence suggests both acute and longer-lasting positive effects of transcranial direct current stimulation (tDCS) on vigilance and sleepiness in hypersomniac patients. Based on these findings, the present study sought to investigate short-term effects of single sessions of tDCS and transcranial random noise stimulation (tRNS) on sleepiness in persons suffering from hypersomnia. Methods: A sample of 29 patients suffering from narcolepsy or idiopathic hypersomnia (IH) was recruited from the Regensburg Sleep Disorder Center and underwent single sessions of tES (anodal tDCS, tRNS, sham) over the left and right dorsolateral prefrontal cortex on three consecutive days in a double-blind, sham-controlled, pseudorandomized crossover trial. The primary study endpoint was the mean reaction time measured by the Psychomotor Vigilance Task (PVT) before and directly after the daily tES sessions. Secondary endpoints were additional PVT outcome metrics as well as subjective outcome parameters (e.g., Karolinska Sleepiness Scale; KSS). Results: There were no significant treatment effects neither on objective (i.e., PVT) nor on subjective indicators of sleepiness. Conclusion: We could not demonstrate any clinically relevant effects of single sessions of tDCS or tRNS on objective or subjective measures of sleepiness in patients with hypersomnia. However, we cannot exclude that repeated sessions of tES may affect vigilance or sleepiness in hypersomniac patients.

Effects of transcranial direct current stimulation and transcranial random noise stimulation on working memory and task-related EEG in major depressive disorder.

OBJECTIVE: To compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD). METHODS: Using a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance. RESULTS: tDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation. CONCLUSIONS: Although tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD. SIGNIFICANCE: This reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals.

Corrigendum: Efficacy of non-invasive brain stimulation for disorders of consciousness: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fnins.2023.1219043.].

Phylogeography and ecological niche modeling implicate multiple microrefugia of Swertia tetraptera during quaternary glaciations.

BACKGROUND: Climate fluctuations during the Pleistocene and mountain uplift are vital driving forces affecting geographic distribution. Here, we ask how an annual plant responded to the Pleistocene glacial cycles. METHODS: In this study, we analyzed the population demographic history of the annual herb Swertia tetraptera Maxim (Gentianaceae) endemic to Qinghai-Tibetan Plateau (QTP). A total of 301 individuals from 35 populations of S. tetraptera were analyzed based on two maternally inherited chloroplast fragments (trnL-trnF and trnS-trnG). Phylogeographic analysis was combined with species distribution modeling to detect the genetic variations in S. tetraptera. RESULTS: The genetic diversity of S. tetraptera was high, likely due to its wide natural range, high proportion of endemic haplotypes and evolutionary history. Fifty-four haplotypes were identified in S. tetraptera. Only a few haplotypes were widespread (Hap_4, Hap_1, Hap_3), which were dispersed throughout the present geographical range of S. tetraptera, while many haplotypes were confined to single populations. The cpDNA dataset showed that phylogeographic structuring was lacking across the distribution range of S. tetraptera. Analyses of molecular variance showed that most genetic variation was found within populations (70.51%). In addition, the relationships of the haplotypes were almost completely unresolved by phylogenetic reconstruction. Both mismatch distribution analysis and neutrality tests showed a recent expansion across the distribution range of S. tetraptera. The MaxEnt analysis showed that S. tetraptera had a narrow distribution range during the Last Glacial Maximum (LGM) and a wide distribution range during the current time, with predictions into the future showing the distribution range of S. tetraptera expanding. CONCLUSION: Our study implies that the current geographic and genetic distribution of S. tetraptera is likely to have been shaped by Quaternary periods. Multiple microrefugia of S. tetraptera existed during Quaternary glaciations. Rapid intraspecific diversification and hybridization and/or introgression may have played a vital role in shaping the current distribution patterns of S. tetraptera. The distribution range of S. tetraptera appeared to have experienced contraction during the LGM; in the future, when the global climate becomes warmer with rising carbon dioxide levels, the distribution of S. tetraptera will expand.

The effect of emotion intensity on time perception: a study with transcranial random noise stimulation.

Emotional facial expressions provide cues for social interactions and emotional events can distort our sense of time. The present study investigates the effect of facial emotional stimuli of anger and sadness on time perception. Moreover, to investigate the causal role of the orbitofrontal cortex (OFC) in emotional recognition, we employed transcranial random noise stimulation (tRNS) over OFC and tested the effect on participants' emotional recognition as well as on time processing. Participants performed a timing task in which they were asked to categorize as "short" or "long" temporal intervals marked by images of people expressing anger, sad or neutral emotional facial expressions. In addition, they were asked to judge if the image presented was of a person expressing anger or sadness. The visual stimuli were facial emotional stimuli indicating anger or sadness with different degrees of intensity at high (80%), medium (60%) and low (40%) intensity, along with neutral emotional face stimuli. In the emotional recognition task, results showed that participants were faster and more accurate when emotional intensity was higher. Moreover, tRNS over OFC interfered with emotion recognition, which is in line with its proposed role in emotion recognition. In the timing task, participants overestimated the duration of angry facial expressions, although neither emotional intensity not OFC stimulation significantly modulated this effect. Conversely, as the emotional intensity increased, participants exhibited a greater tendency to overestimate the duration of sad faces in the sham condition. However, this tendency disappeared with tRNS. Taken together, our results are partially consistent with previous findings showing an overestimation effect of emotionally arousing stimuli, revealing the involvement of OFC in emotional distortions of time, which needs further investigation.

Efficacy of non-invasive brain stimulation for disorders of consciousness: a systematic review and meta-analysis.

Objective: The aim of this study is to evaluate the efficacy of non-invasive brain stimulation (NIBS) in patients with disorders of consciousness (DoC) and compare differences in efficacy between different stimulation modalities. Methods: We searched the PubMed, Cochrane Library, Web of Science, and EMBASE databases for all studies published in English from inception to April 2023. Literature screening and quality assessment were performed independently by two investigators. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to evaluate the therapeutic effects of NIBS. The Cochrane Q test and I2 statistic were used to evaluate heterogeneity between studies. Subgroup analysis was performed to identify the source of heterogeneity, and differences in efficacy between different stimulation modalities were compared by Bayesian analysis. Results: A total of 17 studies with 377 DoC patients were included. NIBS significantly improved the state of consciousness in DoC patients when compared to sham stimulation (WMD: 0.81; 95% CI: 0.46, 1.17; I2 = 78.2%, p = 0.000). When divided into subgroups according to stimulation modalities, the heterogeneity of each subgroup was significantly lower than before (I2: 0.00-30.4%, p >0.05); different stimulation modalities may be the main source of such heterogeneity. Bayesian analysis, based on different stimulation modalities, indicated that a patient's state of consciousness improved most significantly after repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Diagnosis-based subgroup analysis showed that NIBS significantly improved the state of consciousness in patients with a minimal consciousness state (WMD: 1.11; 95% CI: 0.37, 1.86) but not in patients with unresponsive wakefulness syndrome or a vegetative state (WMD: 0.31; 95% CI: -0.09, 0.71). Subgroup analysis based on observation time showed that single treatment did not improve the state of consciousness in DoC patients (WMD: 0.28; 95% CI: -0.27, 0.82) while multiple treatments could (WMD: 1.05; 95% CI: 0.49, 1.61). Furthermore, NIBS had long-term effects on DoC patients (WMD: 0.79; 95% CI: 0.08-1.49). Conclusion: Available evidence suggests that the use of NIBS on patients with DoC is more effective than sham stimulation, and that rTMS of the left DLPFC may be the most prominent stimulation modality.

The role of the parietal lobe in task-irrelevant suppression during learning.

BACKGROUND: Attention optimizes the selection of visual information, while suppressing irrelevant visual input through cortical mechanisms that are still unclear. We set to investigate these processes using an attention task with an embedded to-be-ignored interfering visual input. OBJECTIVE: We delivered electrical stimulation to attention-related brain areas to modulate these facilitatory/inhibitory attentional mechanisms. We asked whether overtly training on a task while being covertly exposed to visual features from a visually identical but different task tested at baseline might influence post-training performance on the baseline task. METHODS: In Experiment one, at baseline subjects performed an orientation discrimination (OD) task using a pair of gratings presented at individual's psychophysical threshold. We then trained participants over three-day separate sessions on a temporal order judgment task (TOJ), using the exact same gratings but presented with different time offsets. On the last post-training session we re-tested OD. We coupled training with transcranial random noise stimulation (tRNS) over the parietal cortex, the human middle temporal area or sham, in three separate groups. In Experiment two, subjects performed the same OD task at baseline and post-training, while tRNS was delivered at rest during the same sessions and stimulation conditions as in Experiment one. RESULTS: Results showed that tRNS over parietal cortex facilitated learning of the trained TOJ task. Moreover, we found a detrimental effect on the untrained OD task when subjects received parietal tRNS coupled with training (Experiment one), but a benefit on OD when subjects received stimulation while at rest (Experiment two). CONCLUSIONS: These results clearly indicate that task-irrelevant information is actively suppressed during learning, and that this prioritization mechanism of selection likely resides in the parietal cortex.

Erratum: Convergent morphological evolution in Silene Sect. Italicae (Caryophyllaceae) in the Mediterranean Basin.

[This corrects the article DOI: 10.3389/fpls.2022.695958.].

State of the art: non-invasive electrical stimulation for the treatment of chronic tinnitus.

Subjective tinnitus is the perception of sound in the absence of external stimulation. Neuromodulation is a novel method with promising properties for application in tinnitus management. This study sought to review the types of non-invasive electrical stimulation in tinnitus to provide the foothold for further research. PubMed, EMBASE, and Cochrane databases were searched for studies on the modulation of tinnitus by non-invasive electrical stimulation. Among the four forms of non-invasive electrical modulation, transcranial direct current stimulation, transcranial random noise stimulation, and transauricular vagus nerve stimulation yielded promising results, whereas the effect of transcranial alternating current stimulation in the treatment of tinnitus has not been confirmed. Non-invasive electrical stimulation can effectively suppress tinnitus perception in some patients. However, the heterogeneity in parameter settings leads to scattered and poorly replicated findings. Further high-quality studies are needed to identify optimal parameters to develop more acceptable protocols for tinnitus modulation.

Noise in the brain: Transcranial random noise stimulation and perceptual noise act on a stochastic resonance-like mechanism.

Stochastic resonance (SR) is a phenomenon in which a certain amount of random noise added to a weak subthreshold stimulus can enhance signal detectability. It is unknown how external noise interacts with neural noise in producing an SR-like phenomenon and whether this interaction results in a modulation of either network efficiency or the efficiency of single neurons. Using random dot motion stimuli and noninvasive brain stimulation, we attempted to unveil the specific mechanism of action of the SR-like phenomenon in motion perception, if present. We aimed to determine whether signal integration efficiency changes with external noise (random dot numerosity) and how electrical transcranial random noise stimulation (tRNS) can affect the peak performance. The participants performed a coherent motion detection task in which the random dot numerosity varied, whereas the signal-to-noise ratio (SNR) remained constant. We applied placebo or tRNS with an amplitude of either 1 or 2 mA during task execution. We found peaks in participants' performance both in the case of placebo stimulation and in the case of 1-mA tRNS. In the latter case (i.e., with an additional noise source), the peak emerged at lower random dot numerosity levels than when no additional noise was added (placebo). No clear peak was observed with 2-mA tRNS. An equivalent noise (EN) analysis confirmed that SR arises from a modulation of the network efficiency underlying motion signal integration. These results indicate a joint contribution of external and neural noise (modulated by tRNS) in eliciting an SR-like phenomenon.

New Taxonomic Arrangement of Dicranella s.l. and Aongstroemia s.l. (Dicranidae, Bryophyta).

The recent molecular phylogenetic study of the families Aongstroemiaceae and Dicranellaceae, which resolved the genera Aongstroemia and Dicranella as polyphyletic, indicated the need for changes in their circumscription and provided new morphological evidence to support the formal description of newly recognized lineages. Following up on these results, the present study adds another molecular marker, the highly informative trnK-psbA region, to a subset of previously analyzed taxa and presents molecular data from newly analyzed austral representatives of Dicranella and collections of Dicranella-like plants from North Asia. The molecular data are linked with morphological traits, particularly the leaf shape, tuber morphology, and capsule and peristome characters. Based on this multi-proxy evidence, we propose three new families (Dicranellopsidaceae, Rhizogemmaceae, and Ruficaulaceae) and six new genera (Bryopalisotia, Calcidicranella, Dicranellopsis, Protoaongstroemia, Rhizogemma, and Ruficaulis) to accommodate the described species according to the revealed phylogenetic affinities. Additionally, we amend the circumscriptions of the families Aongstroemiaceae and Dicranellaceae, as well as the genera Aongstroemia and Dicranella. In addition to the monotypic Protoaongstroemia that contains the newly described dicranelloid plant with a 2-3-layered distal leaf portion from Pacific Russia, P. sachalinensis, Dicranella thermalis is described for a D. heteromalla-like plant from the same region. Fourteen new combinations, including one new status change, are proposed.

Transcranial random noise stimulation over the left dorsolateral prefrontal cortex attenuates pain expectation and perception.

OBJECTIVE: The dorsolateral prefrontal cortex (DLPFC) has been increasingly used as a neuromodulatory target in pain management. Transcranial random noise stimulation (tRNS) was shown to effectively elevate cortical excitability. Hence, this study aimed to characterize how tRNS over the left DLPFC affects pain expectation and perception, as well as the efficacy of conditioned-pain modulation (CPM) that reflects the function of the endogenous pain-inhibitory pathway. METHODS: Using a randomized, double-blinded, and sham-controlled design, healthy participants were randomly recruited to receive tRNS with a direct current offset or sham stimulation. Their expectations and perceptions of painful electrocutaneous stimuli, as well as CPM efficacy were assessed before, immediately after, and 30 min after tRNS. RESULTS: Compared with sham stimulation, perceived-pain ratings to the painful stimuli, and expected-pain ratings before painful stimuli, attenuated immediately after tRNS, whereas this analgesic effect was ineffective 30 min after tRNS. Importantly, the immediate analgesia induced by tRNS could be accounted for by tRNS effect on attenuating expected-pain ratings before certain painful stimuli. However, CPM efficacy was not significantly affected by tRNS. CONCLUSIONS: These results demonstrate analgesia immediately after applying tRNS over the left DLPFC. SIGNIFICANCE: This study provides evidence for analgesia of DLPFC-tRNS on an experimental pain model.

Dynamic sensitivity analysis: Defining personalised strategies to drive brain state transitions via whole brain modelling.

Traditionally, in neuroimaging, model-free analyses are used to find significant differences between brain states via signal detection theory. Depending on the a priori assumptions about the underlying data, different spatio-temporal features can be analysed. Alternatively, model-based techniques infer features from the data and compare significance from model parameters. However, to assess transitions from one brain state to another remains a challenge in current paradigms. Here, we introduce a "Dynamic Sensitivity Analysis" framework that quantifies transitions between brain states in terms of stimulation ability to rebalance spatio-temporal brain activity towards a target state such as healthy brain dynamics. In practice, it means building a whole-brain model fitted to the spatio-temporal description of brain dynamics, and applying systematic stimulations in-silico to assess the optimal strategy to drive brain dynamics towards a target state. Further, we show how Dynamic Sensitivity Analysis extends to various brain stimulation paradigms, ultimately contributing to improving the efficacy of personalised clinical interventions.