Transcranial direct current stimulation versus intermittent theta-burst stimulation for the improvement of working memory performance

Non-invasive brain stimulation (NIBS) techniques have been increasingly used over the dorsolateral prefrontal cortex (DLPFC) to enhance working memory (WM) performance. Notwithstanding, NIBS protocols have shown either small or inconclusive cognitive effects on healthy and neuropsychiatric samples. Therefore, we assessed working memory performance and safety of transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and both therapies combined vs placebo over the neuronavigated left DLPFC of healthy participants. Twenty-four subjects were included to randomly undergo four sessions of NIBS, once a week: tDCS alone, iTBS alone, combined interventions and placebo. The 2-back task and an adverse effect scale were applied after each NIBS session. Results revealed a significantly faster response for iTBS (b= -21.49, p= 0.04), but not for tDCS and for the interaction tDCS vs. iTBS (b= 13.67, p= 0.26 and b= 40.5, p= 0.20, respectively). No changes were observed for accuracy and no serious adverse effects were found among protocols. Although tolerable, an absence of synergistic effects for the combined protocol was seen. Nonetheless, future trials accessing different outcomes for the combined protocols, as well as studies investigating iTBS over the left DLPFC for cognition and exploring sources of variability for tDCS are encouraged.     

Testing the involvement of the prefrontal cortex in lucid dreaming: A tDCS study

Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to increase dream lucidity. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants’ self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed.     

Stimulating Creativity: Modulation of Convergent and Divergent Thinking by Transcranial Direct Current Stimulation (tDCS)

Creativity has been conceptualized as involving 2 distinct components; divergent thinking, the search for multiple solutions to a single problem, and convergent thinking, the quest for a single solution either through an analytical process or the experience of insight. Studies have demonstrated that these abilities can be improved by cognitive stimulation, mood, and meditation. This investigation examined whether convergent and divergent thinking can be enhanced by noninvasive transcranial direct current stimulation (tDCS). In different sessions, participants received bilateral stimulation over the dorsolateral prefrontal cortex—DLPFC (Experiment1) and over the posterior parietal cortex–PPC (Experiment2), while performing the Compound Remote Associative task (CRA) assessing convergent thinking and the Alternative Uses Task (AUT) assessing divergent thinking. In Experiment1, anodal-left cathodal-right stimulation over the DLPFC significantly enhanced CRA performance. In Experiment2, stimulations over the PPC significantly increased insight solutions and decreased analytical solutions compared to the no stimulation condition. These findings provide direct evidence for the role of the left DLPFC in convergent and divergent thinking and a mediating role of the PPC in problem-solving behavior, presumably through attentional processes. From a methodological perspective, brain stimulation can be used as a tool to modulate and to explore components of creativity.     

Enhancing Creativity With Combined Transcranial Direct Current and Random Noise Stimulation of the Left Dorsolateral Prefrontal Cortex and Inferior Frontal Gyrus

Creativity is a fundamental human accomplishment from scientific advances to composing music. The left dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) are important metacontrol hubs in flexibility and persistence brain states, respectively. Those hubs are related to divergent thinking, insight problem-solving, and convergent thinking. In this double-blind, between-subjects study, 81 healthy participants were randomly assigned to one of three groups (n = 27) that received a combined transcranial direct current stimulation–transcranial random noise stimulation (tDCS-tRNS) protocol with the anode over the left DLPFC and cathode over the left IFG (+DLPFC−IFG), the opposite montage (−DLPFC+IFG), and a sham group (+DLPFC−IFG). Both active tDCS-tRNS groups received 20 min of 1 mA tDCS with 1 mA (100–500 Hz) tRNS. Creativity was assessed before (baseline) and during stimulation with the Unusual Uses, Picture Completion (PC), Remote Association test (RAT), Matchstick Arithmetic (MA), and Nine-dot (ND) problems. Only the +DLPFC−IFG group had significantly higher scores compared with sham in the RAT (p = .009), PC fluency (p = .018), PC originality (p = .007), ND (p = .007), and MA (p = .032). Overall, −DLPFC+IFG had greater scores in all creativity tests compared with sham. Implications from the metacontrol theory are discussed.     

Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis

Recent studies have used non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), to increase dorsolateral prefrontal cortex (DLPFC) activity and, consequently, working memory (WM) performance. However, such experiments have yielded mixed results, possibly due to small sample sizes and heterogeneity of outcomes. Therefore, our aim was to perform a systematic review and meta-analyses on NIBS studies assessing the n-back task, which is a reliable index for WM. From the first data available to February 2013, we looked for sham-controlled, randomized studies that used NIBS over the DLPFC using the n-back task in PubMed/MEDLINE and other databases. Twelve studies (describing 33 experiments) matched our eligibility criteria. Active vs. sham NIBS was significantly associated with faster response times (RTs), higher percentage of correct responses and lower percentage of error responses. However, meta-regressions showed that tDCS (vs. rTMS) presented only an improvement in RT, and not in accuracy. This could have occurred in part because almost all tDCS studies employed a crossover design, possibly due to the reliable tDCS blinding. Study design was also associated with no improvement in correct responses in the active vs. sham groups. To conclude, rTMS of the DLPFC significantly improved all measures of WM performance whereas tDCS significantly improved RT, but not the percentage of correct and error responses. Mechanistic insights on the role of DLPFC in WM are further discussed, as well as how NIBS techniques could be used in neuropsychiatric samples presenting WM deficits, such as major depression, dementia and schizophrenia.     

Noninvasive brain stimulation over M1 and DLPFC cortex enhances the learning of bimanual isometric force control

Motor learning plays an important role in upper-limb function and the recovery of lost functionality. This study aimed to investigate the relative impact of transcranial direct current stimulation (tDCS) on learning in relation to the left primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC) during bimanual isometric force-control tasks performed with both hands under different task constraints. In a single-blind cross-over design, 20 right-handed participants were randomly assigned to either the M1 group (n = 10; mean age, 22.90 ± 1.66 years, mean ± standard deviation) or the DLPFC group (n = 10; mean age, 23.20 ± 1.54 years). Each participant received 30 min of tDCS (anodal or sham, applied randomly in two experiments) while performing the bimanual force control tasks. Anodal tDCS of the M1 improved the accuracy of maintenance and rhythmic alteration of force tasks, while anodal tDCS of the DLPFC improved only the maintenance of the force control tasks compared with sham tDCS. Hence, tDCS over the left M1 and DLPFC has a beneficial effect on the learning of bimanual force control.     

Dorsolateral prefrontal cortex mediates working memory processes in motor skill learning

Neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) is recruited during motor skill learning, which suggests the involvement of the DLPFC in working memory (WM) processes, such as selection and integration of motor representations temporarily stored in WM. However, direct evidence linking activation of the DLPFC to WM storage and manipulation during motor skill learning in real-time is rare. In this study, we conducted two experiments to investigate the causal role of DLPFC activity in WM storage and manipulation during motor skill learning under low and high WM-demand conditions. Participants received continuous theta burst stimulation (cTBS) and sham stimulation (crossover design) over the left DLPFC (experiment 1) or right DLPFC (experiment 2). Before and after stimulation, participants in both experiments performed a sequential finger-tapping (SFT) task containing repeated sequence (low-WM demand) and non-repeated sequence (high-WM demand) conditions which are used to study WM processes. The number of correct sequences (NoCS) and reproduction error rate were analyzed. Learning gains in NoCS improved significantly with the practice for both sequence types in the presence of either stimulation type. Compared to sham stimulation, cTBS over the left DLPFC resulted in significantly reduced learning gains in NoCS for non-repeated sequences. These results suggest that the left DLPFC contributes to WM manipulation during motor skill learning.     

工作记忆刷新及其训练效应——经颅直流电刺激的作用

工作记忆刷新是执行功能的重要成分之一。以往研究结合n-back任务和经颅直流电刺激（transcranial direct current stimulation ,tDCS）技术探究刷新能力,发现tDCS技术能够一定程度上增强刷新训练效果并引起大脑神经元相关活动的变化,其增强效果能够维持一定的时间,且能够迁移到其他认知任务之中。但tDCS的干预效果在各项研究中存在一定的差异性。其作用效果会受到训练任务与训练方式、电流强度、电极布局和训练时间间隔等因素的影响。未来研究可以探索tDCS结合刷新训练的最佳刺激参数,以获得最优化的干预效果。     

Alteration of hypnotic experience following transcranial electrical stimulation of the left prefrontal cortex

BackgroundRecent studies of neurostimulation reported alteration of hypnotizability and hypnotic phenomena after inhibition of the dorsolateral prefrontal cortex (DLPFC), but the different assessments of hypnosis and the stimulation parameters still left open many questions about the role of this brain region in hypnotizability. We aimed to administer inhibitory transcranial direct current stimulation (tDCS) over the left DLPFC to observe effects of stimulation on the hypnotic experience and the feeling of agency.Methodsa procedure of hypnotic induction with suggestions was repeated twice: before and after the unilateral cathodal tDCS over the left DLPFC. The experience was assessed through a phenomenological assessment of hypnosis and sense of agency in thirty-three participants randomly assigned to the sham or the active group.Resultsactive (inhibitory) tDCS enhanced the hypnotizability by 15.4% and altered a few dimensions of consciousness such as self-awareness and absorption. No changes emerged on the feeling of agency and pass rates for suggestions.ConclusionstDCS reflects a promising tool to alter the hypnotic phenomena and the responsiveness to hypnotic procedures. Neurocognitive implications are discussed for the construct of hypnotizability as well as for the role of the left DLPFC in the dimensions of consciousness such as self-awareness.     

Poststimulation time interval-dependent effects of motor cortex anodal tDCS on reaction-time task performance

Anodal transcranial direct current stimulation (tDCS) induces long-term potentiation-like plasticity, which is associated with long-lasting effects on different cognitive, emotional, and motor performances. Specifically, tDCS applied over the motor cortex is considered to improve reaction time in simple and complex tasks. The timing of tDCS relative to task performance could determine the efficacy of tDCS to modulate performance. The aim of this study was to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min) applied over the left primary motor cortex (M1) versus sham stimulation on performance of a go/no-go simple reaction-time task carried out at three different time points after tDCS—namely, 0, 30, or 60 min after stimulation. Performance zero min after anodal tDCS was improved during the whole course of the task. Performance 30 min after anodal tDCS was improved only in the last block of the reaction-time task. Performance 60 min after anodal tDCS was not significantly different throughout the entire task. These findings suggest that the motor cortex excitability changes induced by tDCS can improve motor responses, and these effects critically depend on the time interval between stimulation and task performance.     

Short theta burst stimulation to left frontal cortex prior to encoding enhances subsequent recognition memory

Deep semantic encoding of verbal stimuli can aid in later successful retrieval of those stimuli from long-term episodic memory. Evidence from numerous neuropsychological and neuroimaging experiments demonstrate regions in left prefrontal cortex, including left dorsolateral prefrontal cortex (DLPFC), are important for processes related to encoding. Here, we investigated the relationship between left DLPFC activity during encoding and successful subsequent memory with transcranial magnetic stimulation (TMS). In a pair of experiments using a 2-session within-subjects design, we stimulated either left DLPFC or a control region (Vertex) with a single 2-s train of short theta burst stimulation (sTBS) during a semantic encoding task and then gave participants a recognition memory test. We found that subsequent memory was enhanced on the day left DLPFC was stimulated, relative to the day Vertex was stimulated, and that DLPFC stimulation also increased participants’ confidence in their decisions during the recognition task. We also explored the time course of how long the effects of sTBS persisted. Our data suggest 2 s of sTBS to left DLPFC is capable of enhancing subsequent memory for items encoded up to 15 s following stimulation. Collectively, these data demonstrate sTBS is capable of enhancing long-term memory and provide evidence that TBS protocols are a potentially powerful tool for modulating cognitive function.     

Neurocognitive mechanisms behind emotional attention: Inverse effects of anodal tDCS over the left and right DLPFC on gaze disengagement from emotional faces

Background

Attention to relevant emotional information in the environment is an important process related to vulnerability and resilience for mood and anxiety disorders. In the present study, the effects of left and right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional mechanisms of emotional processing were tested and contrasted.

Methods

A sample of 54 healthy participants received 20 min of active and sham anodal transcranial direct current stimulation (i.e., tDCS) either of the left (n = 27) or of the right DLPFC (n = 27) on two separate days. The anode electrode was placed over the left or the right DLPFC, the cathode over the corresponding contra lateral supraorbital area. After each neurostimulation session, participants completed an eye-tracking task assessing direct processes of attentional engagement towards and attentional disengagement away from emotional faces (happy, disgusted, and sad expressions).

Results

Compared to sham, active tDCS over the left DLPFC led to faster gaze disengagement, whereas active tDCS over the right DLPFC led to slower gaze disengagement from emotional faces. Between-group comparisons showed that such inverse change patterns were significantly different and generalized for all types of emotion.

Conclusions

Our findings support a lateralized role of left and right DLPFC activity in enhancing/worsening the top-down regulation of emotional attention processing. These results support the rationale of new therapies for affective disorders aimed to increase the activation of the left over the right DLPFC in combination with attentional control training, and identify specific target attention mechanisms to be trained.

     

Effects of tDCS over the right DLPFC on attentional disengagement from positive and negative faces: An eye-tracking study

The aim of this study was to increase insight in the neural substrates of attention processes involved in emotion regulation. The effects of right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional processing of emotional information were evaluated. A novel attention task allowing a straightforward measurement of attentional engagement toward, and attentional disengagement away from emotional faces was used. A sample of healthy participants received 20 minutes of active and sham anodal transcranial direct current stimulation (i.e., tDCS) applied over the right DLPFC on 2 separate days and completed the attention task after receiving real or sham stimulation. Compared to sham stimulation, tDCS over the right DLPFC led to impairments in attentional disengagement from both positive and negative faces. Findings demonstrate a causal role of right DLPFC activity in the generation of attentional impairments that are implicated in emotional disturbances such as depression and anxiety.     

Transcranial Direct Current Stimulation of the Left Temporal Lobe Modulates Insight

Creativity is the ability to come up with new and original solutions to problems. It is characterized along a dipole spectrum, with the opposing ends defined as convergent and divergent thinking. Previous studies have provided evidence that various cognitive functions and insight into non-verbal problems can be enhanced using non-invasive brain stimulation. The aim of this pilot study was to investigate whether convergent and divergent thinking, as well as insight, can be modulated by transcranial direct current stimulation (tDCS) over the anterior temporal lobe (ATL). Bilateral tDCS (1.5 mA, 20 minutes) was used to modulate activity of the right (AR tDCS) and the left (AL tDCS) ATL. Twenty-one participants performed a divergent thinking test (DTT) during tDCS, while a Remote Associates Task (RAT) was administered before and after tDCS to assess convergent thinking. A control experiment, using a Simple Reaction Time (SRT) Task, was conducted in 10 subjects before and after ATL tDCS in order to investigate whether its effects reflect attention or motor effects on the dominant hand. Results from this preliminary study showed that AL tDCS reduced RAT reaction times (RTs) by 20%. Both AL and AR tDCS did not change RAT accuracy, or the DTT total or sub-item scores. No differences were found in the SRT task after either AL or AR tDCS. These findings suggest that left but not right ATL is involved in convergent thinking. Conversely, both left and right temporal cortex tDCS-induced excitability changes failed to modulate divergent thinking. Limitations are discussed.     

Can transcranial direct current stimulation (tDCS) of the cerebellum improve implicit social and cognitive sequence learning?

Accumulating evidence shows that the posterior cerebellum is involved in mentalizing inferences of social events by detecting sequence information in these events, and building and updating internal models of these sequences. By applying anodal and sham cerebellar transcranial direct current stimulation (tDCS) on the posteromedial cerebellum of healthy participants, and using a serial reaction time (SRT) task paradigm, the current study examined the causal involvement of the cerebellum in implicitly learning sequences of social beliefs of others (Belief SRT) and non-social colored shapes (Cognitive SRT). Apart from the social or cognitive domain differences, both tasks were structurally identical. Results of anodal stimulation (i.e., 2 mA for 20 min) during the social Belief SRT task, did not show significant improvement in reaction times, however it did reveal generally faster responses for the Cognitive SRT task. This improved performance could also be observed after the cessation of stimulation after 30 min, and up to one week later. Our findings suggest a general positive effect of anodal cerebellar tDCS on implicit non-social Cognitive sequence learning, supporting a causal role of the cerebellum in this learning process. We speculate that the lack of tDCS modulation of the social Belief SRT task is due to the familiar and overlearned nature of attributing social beliefs, suggesting that easy and automatized tasks leave little room for improvement through tDCS.     

经颅直流电刺激技术在增强健康个体认知功能中的应用及其影响因素

经颅直流电刺激作为一种无创脑刺激技术,已在临床治疗及康复领域有广泛应用。随着研究的深入和人类对于自身认知需求的提高,近年来也有研究者开始尝试使用该技术增强健康个体的认知功能。本文从感知觉、注意、记忆、学习和复杂任务五个方面对目前经颅直流电刺激技术在健康个体认知增强领域的研究现状进行梳理和总结,讨论了机制和影响因素,以及未来面临的问题和挑战。     

Transcranial direct-current stimulation enhances implicit motor sequence learning in persons with Parkinson's disease with mild cognitive impairment

Implicit motor sequence learning (IMSL) is affected in Parkinson's disease (PD). Research in healthy young participants shows the potential for transcranial direct-current stimulation (tDCS) over the primary motor cortex (M1) to enhance IMSL. In PD, only null effects have been reported to date. We determined concurrent, short-term, and long-term effects of anodal tDCS over M1 on IMSL, as measured by the serial reaction time (SRT) task, in persons with PD with mild cognitive impairment (MCI). Concurrent (anodal/sham tDCS intervention during the SRT task), short-term (5 min post-intervention), and long-term (1 week post-intervention) effects on IMSL were evaluated in persons with idiopathic PD (Hoehn and Yahr stage II-III) with MCI. Results of 11 persons with PD (8 men and 3 women; mean age = 77.1 years; mean disease duration = 7.7 years) showed significant IMSL in the anodal (p = .016), but not in the sham tDCS condition (p = .937). Post-hoc analyses showed that IMSL reached statistical significance at 1 week post-intervention (p < .001). Anodal tDCS over M1 exerted beneficial effects on IMSL in persons with PD with MCI, in particular one week post-intervention. Our study is the first to report a positive effect of tDCS on IMSL in PD. Further research should include a larger, more cognitively diverse sample and additional follow-up periods.     

The reaction-time task-rule congruency effect is not affected by working memory load: further support for the activated long-term memory hypothesis

Previous studies claimed that task representation is carried out by the activated long-term memory portion of working memory (WM; Meiran and Kessler in J Exp Psychol Human Percept Perform 34:137–157, 2008). The present study provides a more direct support for this hypothesis. We used the reaction-time task-rule congruency effect (RT-TRCE) in a task-switching setup, and tested the effects of loading WM with irrelevant task rules on RT-TRCE. Experiment 1 manipulated WM load in a between-subject design. WM participants performed a color/shape task switching, while having 0, 1 or 3 numerical task rules as WM load. Experiment 2 used a similar load manipulation (1 or 3 rules to load WM) in a within-subject design. Experiment 3 extended these results by loading WM with perceptual tasks that were more similar to the shape/color tasks. The results show that RT-TRCE was not affected by WM load supporting the activated long-term memory hypothesis.     

The effect of bicephalic stimulation of the dorsolateral prefrontal cortex on the attentional bias for threat: A transcranial direct current stimulation study

Previous stimulation studies demonstrated that the dorsolateral prefrontal cortex (DLPFC) is involved in threat processing. According to a model of emotional processing, an unbalance between the two DLPFCs, with a hyperactivation of right frontal areas, is involved in the processing of negative emotions and genesis of anxiety. In the present study, we investigated the role of the right and left DLPFC in threat processing in healthy women who also completed the State-Trait Anxiety Inventory (STAI). We simultaneously modulated the activity of the right and left dorsolateral prefrontal cortex by applying bicephalic transcranial direct current stimulation (tDCS) before participants completed a modified version of the classic Posner task using threatening and nonthreatening stimuli as spatial cues. Anodal stimulation on the right DLPFC with a simultaneous cathodal stimulation over the left side induced a disengagement bias in individuals with low STAI scores and a facilitation bias in individuals with high STAI scores. Anodal stimulation on the left DLPFC with the simultaneous cathodal stimulation over the right side did not affect threat processing. The findings of the present study provided specific support to the hypothesis that unbalanced activation between left and right hemispheres with enhanced activation of the right DLPFC is critical in early top-down threat processing in healthy individuals.     

经颅直流电刺激在注意缺陷多动障碍治疗中的应用

经颅直流电刺激(tDCS)治疗注意缺陷多动障碍(ADHD)主要是选取患者的背外侧前额叶(DLPFC)作为刺激区域, 通过调节其皮层兴奋性, 从而缓解其ADHD的症状和改善其受损的认知功能。针对tDCS在ADHD治疗研究中的问题, 未来可从有效性、确定最佳刺激参数、个体差异、不同亚型及与其他疗法联合使用等五个方面来进一步研究。