Impact of Anodal and Cathodal Transcranial Direct Current Stimulation over the Left Dorsolateral Prefrontal Cortex during Attention Bias Modification: An Eye-Tracking Study

People with anxiety disorders show an attentional bias for threat (AB), and Attention Bias Modification (ABM) procedures have been found to reduce this bias. However, the underlying processes accounting for this effect remain poorly understood. One explanation suggests that ABM requires the modification of attention control, driven by the recruitment of the dorsolateral prefrontal cortex (DLPFC). In the present double-blind study, we examined whether modifying left DLPFC activation influences the effect of ABM on AB. We used transcranial direct current stimulation (tDCS) to directly modulate cortical excitability of the left DLPFC during an ABM procedure designed to reduce AB to threat. Anodal tDCS increases excitability, whereas cathodal tDCS decreases it. We randomly assigned highly trait-anxious individuals to one of three conditions: 1) ABM combined with cathodal tDCS, 2) ABM combined with anodal tDCS, or 3) ABM combined with sham tDCS. We assessed the effects of these manipulations on both reaction times and eye-movements on a task indexing AB. Results indicate that combining ABM and anodal tDCS over the left DLPFC reduces the total duration that participants’ gaze remains fixated on threat, as assessed using eye-tracking measurement. However, in contrast to previous studies, there were no changes in AB from baseline to post-training for participants that received ABM without tDCS. As the tendency to maintain attention to threat is known to play an important role in the maintenance of anxiety, the present findings suggest that anodal tDCS over the left DLPFC may be considered as a promising tool to reduce the maintenance of gaze to threat. Implications for future translational research combining ABM and tDCS are discussed.     

Modulation of prefrontal cortex with anodal tDCS prevents post-exercise facilitation interference during dual task

In this study we aimed to investigate whether transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) reduces interference effects of a dual task (DT) on post-exercise facilitation (PEF) of the motor evoked potentials. Anodal tDCS reversed the DT interference on PEF after a non-fatiguing isometric contraction. We conclude that anodal DLPFC tDCS improves the ability to allocate attentional resources and modulates plastic adaptations across brain systems.     

Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information

Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC). To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task), and on one cognitive task assessing the ability to adopt another person’s visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal) applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants’ tendency to adopt another’s point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males’ responses to threatening faces whereas it interferes with the ability to adopt another’s viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.     

Modulating Memory Performance in Healthy Subjects with Transcranial Direct Current Stimulation Over the Right Dorsolateral Prefrontal Cortex

Objective

The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task.

Method

36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS.

Results

Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance.

Conclusion

Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects.     

Transcranial Direct Current Stimulation of the Left Dorsolateral Prefrontal Cortex Shifts Preference of Moral Judgments

Attitude to morality, reflecting cultural norms and values, is considered unique to human social behavior. Resulting moral behavior in a social environment is controlled by a widespread neural network including the dorsolateral prefrontal cortex (DLPFC), which plays an important role in decision making. In the present study we investigate the influence of neurophysiological modulation of DLPFC reactivity by means of transcranial direct current stimulation (tDCS) on moral reasoning. For that purpose we administered anodal, cathodal, and sham stimulation of the left DLPFC while subjects judged the appropriateness of hard moral personal dilemmas. In contrast to sham and cathodal stimulation, anodal stimulation induced a shift in judgment of personal moral dilemmas towards more non-utilitarian actions. Our results demonstrate that alterations of left DLPFC activity can change moral judgments and, in consequence, provide a causal link between left DLPFC activity and moral reasoning. Most important, the observed shift towards non-utilitarian actions suggests that moral decision making is not a permanent individual trait but can be manipulated; consequently individuals with boundless, uncontrollable, and maladaptive moral behavior, such as found in psychopathy, might benefit from neuromodulation-based approaches.     

Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS)

Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients.     

Task-specific effects of tDCS-induced cortical excitability changes on cognitive and motor sequence set shifting performance

In this study, we tested the effects of transcranial Direct Current Stimulation (tDCS) on two set shifting tasks. Set shifting ability is defined as the capacity to switch between mental sets or actions and requires the activation of a distributed neural network. Thirty healthy subjects (fifteen per site) received anodal, cathodal and sham stimulation of the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1). We measured set shifting in both cognitive and motor tasks. The results show that both anodal and cathodal single session tDCS can modulate cognitive and motor tasks. However, an interaction was found between task and type of stimulation as anodal tDCS of DLPFC and M1 was found to increase performance in the cognitive task, while cathodal tDCS of DLPFC and M1 had the opposite effect on the motor task. Additionally, tDCS effects seem to be most evident on the speed of changing sets, rather than on reducing the number of errors or increasing the efficacy of irrelevant set filtering.     

Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex Modulates Repetition Suppression to Unfamiliar Faces: An ERP Study

Repeated visual processing of an unfamiliar face suppresses neural activity in face-specific areas of the occipito-temporal cortex. This "repetition suppression" (RS) is a primitive mechanism involved in learning of unfamiliar faces, which can be detected through amplitude reduction of the N170 event-related potential (ERP). The dorsolateral prefrontal cortex (DLPFC) exerts top-down influence on early visual processing. However, its contribution to N170 RS and learning of unfamiliar faces remains unclear. Transcranial direct current stimulation (tDCS) transiently increases or decreases cortical excitability, as a function of polarity. We hypothesized that DLPFC excitability modulation by tDCS would cause polarity-dependent modulations of N170 RS during encoding of unfamiliar faces. tDCS-induced N170 RS enhancement would improve long-term recognition reaction time (RT) and/or accuracy rates, whereas N170 RS impairment would compromise recognition ability. Participants underwent three tDCS conditions in random order at ∼72 hour intervals: right anodal/left cathodal, right cathodal/left anodal and sham. Immediately following tDCS conditions, an EEG was recorded during encoding of unfamiliar faces for assessment of P100 and N170 visual ERPs. The P3a component was analyzed to detect prefrontal function modulation. Recognition tasks were administered ∼72 hours following encoding. Results indicate the right anodal/left cathodal condition facilitated N170 RS and induced larger P3a amplitudes, leading to faster recognition RT. Conversely, the right cathodal/left anodal condition caused N170 amplitude and RTs to increase, and a delay in P3a latency. These data demonstrate that DLPFC excitability modulation can influence early visual encoding of unfamiliar faces, highlighting the importance of DLPFC in basic learning mechanisms.     

Speech facilitation by left inferior frontal cortex stimulation

Electrophysiological studies in humans and animals suggest that noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting [1], polarity-dependent [2] changes in neocortical excitability. Application of tDCS can have significant and selective behavioral consequences that are associated with the cortical location of the stimulation electrodes and the task engaged during stimulation [3-8]. However, the mechanism by which tDCS affects human behavior is unclear. Recently, functional magnetic resonance imaging (fMRI) has been used to determine the spatial topography of tDCS effects [9-13], but no behavioral data were collected during stimulation. The present study is unique in this regard, in that both neural and behavioral responses were recorded using a novel combination of left frontal anodal tDCS during an overt picture-naming fMRI study. We found that tDCS had significant behavioral and regionally specific neural facilitation effects. Furthermore, faster naming responses correlated with decreased blood oxygen level-dependent (BOLD) signal in Broca's area. Our data support the importance of Broca's area within the normal naming network and as such indicate that Broca's area may be a suitable candidate site for tDCS in neurorehabilitation of anomic patients, whose brain damage spares this region.     

Distinct Contributions of the Dorsolateral Prefrontal and Orbitofrontal Cortex during Emotion Regulation

The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC) and the lateral orbitofrontal cortex (OFC) contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.     

Keep Calm and Carry On: Improved Frustration Tolerance and Processing Speed by Transcranial Direct Current Stimulation (tDCS)

Cognitive control (CC) of attention is a major prerequisite for effective information processing. Emotional distractors can bias and impair goal-directed deployment of attentional resources. Frustration-induced negative affect and cognition can act as internal distractors with negative impact on task performance. Consolidation of CC may thus support task-oriented behavior under challenging conditions. Recently, transcranial direct current stimulation (tDCS) has been put forward as an effective tool to modulate CC. Particularly, anodal, activity enhancing tDCS to the left dorsolateral prefrontal cortex (dlPFC) can increase insufficient CC in depression as indicated by a reduction of attentional biases induced by emotionally salient stimuli. With this study, we provide first evidence that, compared to sham stimulation, tDCS to the left dlPFC enhances processing speed measured by an adaptive version of the Paced Auditory Serial Addition Task (PASAT) that is typically thwarted by frustration. Notably, despite an even larger amount of error-related negative feedback, the task-induced upset was suppressed in the group receiving anodal tDCS. Moreover, inhibition of task-related negative affect was correlated with performance gains, suggesting a close link between enhanced processing speed and consolidation of CC by tDCS. Together, these data provide first evidence that activity enhancing anodal tDCS to the left dlPFC can support focused cognitive processing particularly when challenged by frustration-induced negative affect.     

Empathy Moderates the Effect of Repetitive Transcranial Magnetic Stimulation of the Right Dorsolateral Prefrontal Cortex on Costly Punishment

Humans incur considerable costs to punish unfairness directed towards themselves or others. Recent studies using repetitive transcranial magnetic stimulation (rTMS) suggest that the right dorsolateral prefrontal cortex (DLPFC) is causally involved in such strategic decisions. Presently, two partly divergent hypotheses are discussed, suggesting either that the right DLPFC is necessary to control selfish motives by implementing culturally transmitted social norms, or is involved in suppressing emotion-driven prepotent responses to perceived unfairness. Accordingly, we studied the role of the DLPFC in costly (i.e. third party) punishment by applying rTMS to the left and right DLPFC before playing a Dictator Game with the option to punish observed unfair behavior (DG-P). In addition, sham stimulation took place. Individual differences in empathy were assessed with the German version of the Interpersonal Reactivity Index. Costly punishment increased (non-significantly) upon disruption of the right – but not the left – DLPFC as compared to sham stimulation. However, empathy emerged as a highly significant moderator variable of the effect of rTMS over the right, but not left, DLPFC, suggesting that the right DLPFC is involved in controlling prepotent emotional responses to observed unfairness, depending on individual differences in empathy.     

Emotional Meaning in Context in Relation to Hypomanic Personality Traits: An ERP Study

The ability to integrate contextual information is important for the comprehension of emotional and social situations. While some studies have shown that emotional processes and social cognition are impaired in people with hypomanic personality trait, no results have been reported concerning the neurophysiological processes mediating the processing of emotional information during the integration of contextual social information in this population. We therefore chose to conduct an ERP study dealing with the integration of emotional information in a population with hypomanic personality trait. Healthy participants were evaluated using the Hypomanic Personality Scale (HPS), and ERPs were recorded during a linguistic task in which participants silently read sentence pairs describing short social situations. The first sentence implicitly conveyed the positive or negative emotional state of a character. The second sentence was emotionally congruent or incongruent with the first sentence. We analyzed the difference in the modulation of two components (N400 and LPC) in response to the emotional word present at the end of the “target” sentences as a function of the HPS score and the emotional valence of the context. Our results showed a possible modulation of the N400 component in response to both positive and negative context among the participants who scored high on the Mood Volatility subscale of the Hypomanic Personality Scale. These results seem to indicate that the participants with hypomanic personality traits exhibited specificities in the integration of emotions at the level of the early-mobilized neurocognitive processes (N400). Participants with hypomanic personality traits found it difficult to integrate negative emotional contexts, while simultaneously exhibiting an enhanced integration of positive emotional contexts.     

Anodal tDCS over the Motor Cortex on Prepared and Unprepared Responses in Young Adults

Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been proposed as a possible therapeutic rehabilitation technique for motor impairment. However, despite extensive investigation into the effects of anodal tDCS on motor output, there is little information on how anodal tDCS affects response processes. In this study, we used a cued go/nogo task with both directional and non-directional cues to assess the effects of anodal tDCS over the dominant (left) primary motor cortex on prepared and unprepared motor responses. Three experiments explored whether the effectiveness of tDCS varied with timing between stimulation and test. Healthy, right-handed young adults participated in a double-blind randomised controlled design with crossover of anodal tDCS and sham stimulation. In Experiment 1, twenty-four healthy young adults received anodal tDCS over dominant M1 at least 40 mins before task performance. In Experiment 2, eight participants received anodal tDCS directly before task performance. In Experiment 3, twenty participants received anodal tDCS during task performance. In all three experiments, participants responded faster to directional compared to non-directional cues and with their right hand. However, anodal tDCS had no effect on go/nogo task performance at any stimulation – test interval. Bayesian analysis confirmed that anodal stimulation had no effect on response speed. We conclude that anodal tDCS over M1 does not improve response speed of prepared or unprepared responses of young adults in a go/nogo task.     

The role of the DLPFC in inductive reasoning of MCI patients and normal agings: An fMRI study

Previous studies of young people have revealed that the left dorsolateral prefrontal cortex (DLPFC) plays an important role in inductive reasoning. An fMRI experiment was performed in this study to examine whether the left DLPFC was involved in inductive reasoning of MCI patients and normal agings, and whether the activation pattern of this region was different between MCI patients and normal agings. The fMRI results indicated that MCI patients had no difference from normal agings in behavior per-formance (reaction time and accuracy) and the activation pattern of DLPFC. However, the BOLD re-sponse of the DLPFC region for MCI patients was weaker than that for normal agings, and the func-tional connectivity between the bilateral DLPFC regions for MCI patients was significantly higher than for normal agings. Taken together, these results indicated that DLPFC plays an important role in inductive reasoning of agings, and the functional abnormity of DLPFC may be an earlier marker of MCI before structural alterations.     

Improved Working Memory Performance through Self-Regulation of Dorsal Lateral Prefrontal Cortex Activation Using Real-Time fMRI

Working memory is important for a wide range of high-level cognitive activities. Previous studies have shown that the dorsal lateral prefrontal cortex (DLPFC) plays a critical role in working memory and that behavioral training of working memory can alter the activity of DLPFC. However, it is unclear whether the activation in the DLPFC can be self-regulated and whether any self-regulation can affect working memory behavior. The recently emerged real-time functional magnetic resonance imaging (rtfMRI) technique enables the individuals to acquire self-control of localized brain activation, potentially inducing desirable behavioral changes. In the present study, we employed the rtfMRI technique to train subjects to up-regulate the activation in the left DLPFC, which is linked to verbal working memory. After two rtfMRI training sessions, activation in the left DLPFC was significantly increased, whereas the control group that received sham feedback did not show any increase in DLPFC activation. Pre- and post-training behavioral tests indicated that performance of the digit span and letter memory task was significantly improved in the experimental group. Between-group comparison of behavioral changes showed that the increase of digit span in the experimental group was significantly greater than that in the control group. These findings provide preliminary evidence that working memory performance can be improved through learned regulation of activation in associated brain regions using rtfMRI.     

Continuous Theta Burst Stimulation over the Left Dorsolateral Prefrontal Cortex Decreases Medium Load Working Memory Performance in Healthy Humans

The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory. Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC can interfere with working memory performance. Here we investigated for how long continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory performance and whether the effect of cTBS on performance depends on working memory load. Forty healthy young subjects received either cTBS over the left DLPFC or sham stimulation before performing a 2-, and 3-back working memory letter task. An additional 0-back condition served as a non-memory-related control, measuring general attention. cTBS over the left DLPFC significantly impaired 2-back working memory performance for about 15 min, whereas 3-back and 0-back performances were not significantly affected. Our results indicate that the effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min and depends on working memory load.     

Stimulation of the left dorsolateral prefrontal cortex with slow rTMS enhances verbal memory formation

Encoding of episodic memories relies on stimulus-specific information processing and involves the left prefrontal cortex. We here present an incidental finding from a simultaneous EEG-TMS experiment as well as a replication of this unexpected effect. Our results reveal that stimulating the left dorsolateral prefrontal cortex (DLPFC) with slow repetitive transcranial magnetic stimulation (rTMS) leads to enhanced word memory performance. A total of 40 healthy human participants engaged in a list learning paradigm. Half of the participants (N = 20) received 1 Hz rTMS to the left DLPFC, while the other half (N = 20) received 1 Hz rTMS to the vertex and served as a control group. Participants receiving left DLPFC stimulation demonstrated enhanced memory performance compared to the control group. This effect was replicated in a within-subjects experiment where 24 participants received 1 Hz rTMS to the left DLPFC and vertex. In this second experiment, DLPFC stimulation also induced better memory performance compared to vertex stimulation. In addition to these behavioural effects, we found that 1 Hz rTMS to DLPFC induced stronger beta power modulation in posterior areas, a state that is known to be beneficial for memory encoding. Further analysis indicated that beta modulations did not have an oscillatory origin. Instead, the observed beta modulations were a result of a spectral tilt, suggesting inhibition of these parietal regions. These results show that applying 1 Hz rTMS to DLPFC, an area involved in episodic memory formation, improves memory performance via modulating neural activity in parietal regions.

Encoding of episodic memories relies on stimulus-specific information processing and involves the left prefrontal cortex. An incidental finding from a simultaneous EEG-TMS experiment reveals that applying 1-Hz repetitive transcranial magnetic stimulation to this area of the brain improves memory performance by modulating neural activity in parietal regions.     

Electrical Stimulation over Bilateral Occipito-Temporal Regions Reduces N170 in the Right Hemisphere and the Composite Face Effect

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical excitability. Although the clinical value of tDCS has been advocated, the potential of tDCS in cognitive rehabilitation of face processing deficits is less understood. Face processing has been associated with the occipito-temporal cortex (OT). The present study investigated whether face processing in healthy adults can be modulated by applying tDCS over the OT. Experiment 1 investigated whether tDCS can affect N170, a face-sensitive ERP component, with a face orientation judgment task. The N170 in the right hemisphere was reduced in active stimulation conditions compared with the sham stimulation condition for both upright faces and inverted faces. Experiment 2 further demonstrated that tDCS can modulate the composite face effect, a type of holistic processing that reflects the obligatory attention to all parts of a face. The composite face effect was reduced in active stimulation conditions compared with the sham stimulation condition. Additionally, the current polarity did not modulate the effect of tDCS in the two experiments. The present study demonstrates that N170 can be causally manipulated by stimulating the OT with weak currents. Furthermore, our study provides evidence that obligatory attention to all parts of a face can be affected by the commonly used tDCS parameter setting.     

fMRI Study of Social Anxiety during Social Ostracism with and without Emotional Support

Social anxiety is characterized by an excessive fear of being embarrassed in social interactions or social performance situations. Emotional support can help to decrease or diminish social distress. Such support may play an important role at different points of social interaction. However, it is unclear how the beneficial effects of social support are represented in the brains of socially anxious individuals. To explore this, we used the same paradigm previously used to examine the effects of emotional support on social pain caused by exclusion. Undergraduates (n = 46) showing a wide range of social anxiety scores underwent functional magnetic resonance imaging (fMRI) while participating in a Cyberball game. Participants were initially included and later excluded from the game. In the latter half of the session in which participants were excluded, they were provided with supportive messages. In line with our previous work, we found that social exclusion led to increased anterior cingulate cortex (ACC) activity, whereas emotional support led to increased left dorsolateral prefrontal cortex (DLPFC) activity. Despite validation of the paradigm, social anxiety was not associated with increased ACC activity during social exclusion, or during perceived emotional support. Instead, fear of negative evaluation as assessed by the Brief Fear of Negative Evaluation (BFNE) scale showed positive associations with left DLPFC activation while receiving emotional support, compared to while being socially excluded. The more socially anxious an individual was, the greater was the left DLPFC activity increased during receipt of messages. This suggests that highly socially anxious people still have the ability to perceive social support, but that they are nevertheless susceptible to negative evaluation by others.