Improving working memory: Exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex

Objective

The aim of this study was to determine if working memory (WM) performance is significantly improved after the delivery of transcranial random noise stimulation (tRNS) to the left dorsolateral prefrontal cortex (DLPFC), compared to an active comparator or sham.

Methods

Ten participants undertook three experimental sessions in which they received 10 min of anodal tDCS (active comparator), tRNS or sham tDCS whilst performing the Sternberg WM task. Intra-stimulation engagement in a WM task was undertaken as this has been previously shown to enhance the effects of tDCS. Experimental sessions were separated by a minimum of 1 week. Immediately prior to and after each stimulation session the participants were measured on speed and accuracy of performance on an n-back task.

Results

There was significant improvement in speed of performance following anodal tDCS on the 2-back WM task; this was the only significant finding.

Conclusions

The results do not provide support for the hypothesis that tRNS improves WM. However, the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning. Methodological limitations that may have contributed to the lack of significant findings following tRNS are discussed.

Significance

Anodal tDCS may have significant implications for WM remediation in psychiatric conditions, particularly schizophrenia.     

Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex

The midbrain lies deep within the brain and has an important role in reward, motivation, movement and the pathophysiology of various neuropsychiatric disorders such as Parkinson''s disease, schizophrenia, depression and addiction. To date, the primary means of acting on this region has been with pharmacological interventions or implanted electrodes. Here we introduce a new noninvasive brain stimulation technique that exploits the highly interconnected nature of the midbrain and prefrontal cortex to stimulate deep brain regions. Using transcranial direct current stimulation (tDCS) of the prefrontal cortex, we were able to remotely activate the interconnected midbrain and cause increases in participants'' appraisals of facial attractiveness. Participants with more enhanced prefrontal/midbrain connectivity following stimulation exhibited greater increases in attractiveness ratings. These results illustrate that noninvasive direct stimulation of prefrontal cortex can induce neural activity in the distally connected midbrain, which directly effects behavior. Furthermore, these results suggest that this tDCS protocol could provide a promising approach to modulate midbrain functions that are disrupted in neuropsychiatric disorders.     

Effects of transcranial direct current stimulation over the right dorsolateral prefrontal cortex on fairness-related decision-making

Neuroimaging studies suggest that the right dorsolateral prefrontal cortex (rDLPFC) is an important brain area involved in fairness-related decision-making. In the present study, we used transcranial direct current stimulation (tDCS) over the rDLPFC to investigate the effects of changed cortical excitability on fairness norm enforcement in social decision-making. Participants received anodal, cathodal or sham stimulation before performing a modified ultimatum game task, in which participants were asked to accept or reject the proposer’s offer and self-rate the intensity of their anger at offers on a 7-point scale. The results showed that the rejection rate of unfair offers and anger level were higher in the anodal compared to the sham and cathodal groups and that the level of anger at unfair offers can predict the rejection rate. Furthermore, the fairness effect of RTs was more prominent in the anodal group than in the sham and cathodal groups. Our findings validate the causal role of the rDLPFC in fairness-related decision-making through tDCS, suggesting that strengthening the rDLPFC increases individuals’ reciprocal fairness in social decision-making, both in subjective rating and behaviors.     

Transcranial direct current brain stimulation decreases impulsivity in ADHD

Background

Impulsivity is a core deficit in attention deficit hyperactivity disorder (ADHD). Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to modulate cognitive control circuits and could enhance DLPFC activity, leading to improved impulse control in ADHD.

Modulation of cortical responses by transcranial direct current stimulation of dorsolateral prefrontal cortex: A resting-state EEG and TMS-EEG study

Background

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with potential for cost-effective therapeutic neuromodulation. Although positive therapeutic effects were found by stimulating the dorsolateral prefrontal cortex (DLPFC), few studies have investigated physiological effects of DLPFC-tDCS.

Anodal transcranial direct current stimulation over the right dorsolateral prefrontal cortex enhances reflective judgment and decision-making

Background

Accounts of cognitive processes in judgment and decision-making are frequently based on a dual-process framework, which reflects two qualitatively different types of processing: intuitive (Type 1) and analytical (Type 2) processes.

A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique, which can be used to selectively disrupt patterns of neural activity that are associated with symptoms of mental illness. tDCS has been implemented in numerous therapeutic trials across a range of patient populations, with a rapidly increasing number of studies being published each year. This systematic review aimed to evaluate the efficacy of tDCS in the treatment of psychiatric disorders. Four electronic databases were searched from inception until December 2015 by two independent reviewers, and 66 eligible studies were identified. Depression was the most extensively researched condition, followed by schizophrenia and substance use disorders. Data on obsessive compulsive disorder, generalised anxiety disorder, and anorexia nervosa were also obtained. The quality of included studies was appraised using a standardised assessment framework, which yielded a median score corresponding to “weak” on the three-point scale. This improved to “moderate” when case reports/series were excluded from the analysis. Overall, data suggested that tDCS interventions comprising multiple sessions can ameliorate symptoms of several major psychiatric disorders, both acutely and in the long-term. Nevertheless, the tDCS field is still in its infancy, and several methodological and ethical issues must be addressed before clinical efficacy can truly be determined. Studies probing the mechanisms of action of tDCS and those facilitating the definition of optimised stimulation protocols are warranted. Furthermore, evidence from large-scale, multi-centre randomised controlled trials is required if the transition of this therapy from the laboratory to the clinic is to be considered.     

Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: A tDCS‐fMRI study

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task‐related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task‐related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole‐brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole‐brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. Hum Brain Mapp 35:3673–3686, 2014. © 2014 Wiley Periodicals, Inc .     

Regional specificity of cathodal transcranial direct current stimulation (tDCS) effects on spatial-numerical associations: Comparison of four stimulation sites

Based on a theory of impulsive and reflective human behavior, we test the effects of transcranial direct current stimulation (tDCS) targeting either prefrontal or parietal cortex in either hemisphere. In a confirmatory registered report, cathodal tDCS is administered to conceptually reproduce tDCS modulations of implicit spatial-numerical associations, numerical distance effects, and response inhibition. Those cognitive operations are hypothesized to draw on left prefrontal, parietal, and right prefrontal activations, respectively, thereby susceptible to inhibitory, cathodal tDCS across those regions. Vice versa, the mutual regional and behavioral specificity of tDCS effects on these behavioral indices is examined and expected to produce double dissociations. In a mixed within-subjects (baseline, during tDCS, post-tDCS) and between-subjects (target electrode: left/right prefrontal cortex/posterior parietal cortex, or sham tDCS) design, we collect (a) confirmatory data on the robustness of cathodal tDCS effects on three behavioral effects and (b) differential data on the specificity of regional targets in male and female human participants. Results will provide crucial tests of theories of cortical organization implied by implicit associations and explicit regulation, which can direct future brain stimulation studies.     

Cerebellar transcranial direct current stimulation modulates the fMRI signal in the cerebellar nuclei in a simple motor task

BackgroundIn a seminal paper, Galea et al. (Modulation of cerebellar excitability by polarity-specific noninvasive direct current stimulation. 2009. J Neurosci 29, 9115–9122) showed that cerebellar transcranial direct current stimulation (ctDCS) alters cerebellar-M1 connectivity. This effect has been explained by ctDCS-related changes of excitability of the cerebellar cortex with consecutive modulation of its main output, the dentate-thalamo-cortical pathway.ObjectivesThe aim of this functional magnetic resonance imaging (fMRI) study was to provide evidence that cathodal ctDCS decreases the activity of the cerebellar cortex, resulting in increased activity of the cerebellar nuclei, whereas anodal ctDCS has the opposite effect.MethodsA total of 48 participants (female/male: 23/25, age: 23.8 ± 4.1yrs., mean ± standard deviation) performed a finger tapping task with the right hand in a 3T MRI scanner. Functional MR images were acquired prior, during and after tDCS of the right cerebellum. Participants were assigned randomly to anodal, cathodal or sham ctDCS.ResultsNo significant difference of cerebellar cortical activation was found after comparing the three modes of stimulation. On the level of the dentate nuclei, however, a significant increase of activation was detected during and after cathodal stimulation. Furthermore, dentate nuclei activation was suppressed on a trend level following anodal stimulation.ConclusionsThe present findings support the hypothesis that cathodal ctDCS leads to a disinhibition of the dentate nucleus, whereas anodal ctDCS may have the opposite effect.     

Effects of combined theta burst stimulation and transcranial direct current stimulation of the dorsolateral prefrontal cortex on stress

ObjectiveResearch suggests that the combination of different non-invasive brain stimulation techniques, such as intermittent theta-burst stimulation (iTBS) and transcranial direct current stimulation (tDCS), could enhance the effects of stimulation. Studies investigating the combination of tDCS and iTBS over the dorsolateral prefrontal cortex (DLPFC) are lacking. In this within-subjects study, we evaluated the additive effects of iTBS with tDCS on psychophysiological measures of stress.MethodSixty-eight healthy individuals were submitted to a _bifrontaltDCS + iTBS and _shamtDCS + iTBS protocol targeting the DLPFC with a one-week interval. The Maastricht Acute Stress Test was used to activate the stress system after stimulation. Stress reactivity and recovery were assessed using physiological and self-report measures.ResultsThe stressor evoked significant psychophysiological changes in both stimulation conditions. However, no evidence was found for differences between them in stress reactivity and recovery. Participants reported more pain and feelings of discomfort to the _bifrontaltDCS + iTBS protocol.ConclusionIn this study set-up, iTBS plus tDCS was not superior to iTBS in downregulating stress in healthy subjects.SignificanceThere is no evidence for an effect of combined tDCS-iTBS of the DLPFC on stress according to the parameters employed in our study. Future studies should explore other stimulation parameters, additive approaches and/or neurobiological markers.     

Modulation of decision‐making in a gambling task in older adults with transcranial direct current stimulation

Cognitive performance usually declines in older adults as a result of neurodegenerative processes. One of the cognitive domains usually affected is decision‐making. Based on our recent findings suggesting that non‐invasive brain stimulation can improve decision‐making in young participants, we studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex of older adult subjects can change balance of risky and safe responses as it can in younger individuals. Twenty‐eight subjects (age range from 50 to 85 years) performed a gambling risk task while receiving either anodal tDCS over the right and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS over the left with cathodal tDCS over the right DLPFC, or sham stimulation. Our main finding was a significant group effect showing that participants receiving left anodal/right cathodal stimulation chose more often high‐risk prospects as compared with participants receiving sham or those receiving right anodal/left cathodal stimulation. This result is contrary to previous findings in young subjects, suggesting that modulation of cortical activity in young and elderly results in opposite behavioral effects; thus supporting fundamental changes in cognitive processing in the elderly.     

Individual differences in moral judgment competence are related to activity of the prefrontal cortex when attributing blame to evil intention

The weighing of intentions and consequences is inconsistent in adult’s moral judgments, and this is particularly prominent when assigning blame to the immoral intentions in the absence of negative outcomes. The current study extends previous research by examining how individual differences in moral judgment competence are reflected in the cortical network when making judgments about immoral intentions. Twenty-four participants were scanned, using functional magnetic resonance imaging, while making judgments about three kinds of moral scenarios: a neutral condition, an immoral intention condition, and an immoral condition. The result showed that comparing with making judgments about the other two conditions, making judgments about the immoral intentions takes longer time and was associated with significantly elevated activity in the dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex. Additionally, moral judgment competence scores were inversely correlated with activity in the right dorsolateral prefrontal cortex when assigning blame to the immoral intentions. Greater activity in the right dorsolateral prefrontal cortex in participants with lower moral judgment competence possibly reflected increased recruitment of cognitive resource applied to control impulsive response and integrate competitive information in making judgments about the immoral intention.     

Lateral prefrontal/orbitofrontal cortex has different roles in norm compliance in gain and loss domains: a transcranial direct current stimulation study

Sanction is used by almost all known human societies to enforce fairness norm in resource distribution. Previous studies have consistently shown that the lateral prefrontal cortex (lPFC) and the adjacent orbitofrontal cortex (lOFC) play a causal role in mediating the effect of sanction threat on norm compliance. However, most of these studies were conducted in gain domain in which resources are distributed. Little is known about the mechanisms underlying norm compliance in loss domain in which individual sacrifices are needed. Here we employed a modified version of dictator game (DG) and high‐definition transcranial direct current stimulation (HD‐tDCS) to investigate to what extent lPFC/lOFC is involved in norm compliance (with and without sanction threat) in both gain‐ and loss‐sharing contexts. Participants allocated a fixed total amount of monetary gain or loss between themselves and an anonymous partner in multiple rounds of the game. A computer program randomly decided whether a given round involved sanction threat for the participants. Results showed that disruption of the right lPFC/lOFC by tDCS increased the voluntary norm compliance in the gain domain, but not in the loss domain; tDCS on lPFC/lOFC had no effect on compliance under sanction threat in either the gain or loss domain. Our findings reveal a context‐dependent nature of norm compliance and differential roles of lPFC/lOFC in norm compliance in gain and loss domains.     

Shifting set about task switching: behavioral and neural evidence for distinct forms of cognitive flexibility

Task switching is an important aspect of cognitive control and understanding its underlying mechanisms is the focus of considerable research. In this paper, we contrast two different kinds of task switching paradigms and provide evidence that different cognitive mechanisms underlie switching behavior depending on whether the switch is between sets of rules (rule switch) or sets of features presented simultaneously (perceptual switch). In two experiments, we demonstrate that behavioral effects (Experiment 1) and neural recruitment (Experiment 2) vary with the type of switch performed. While perceptual switch costs occurred when the alternative feature set was physically present, rule switch costs were observed even in their absence. Rule switching was also characterized by larger target repetition effects and by greater engagement of the dorsolateral prefrontal cortex. In contrast, perceptual switching was associated with greater recruitment of the parietal cortex. These results provide strong evidence for multiple forms of switching and suggest the limitations of generalizing results across shift types.     

Impact of network-targeted multichannel transcranial direct current stimulation on intrinsic and network-to-network functional connectivity

Dynamics within and between functional resting-state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel, network-targeted transcranial direct current stimulation (net-tDCS), optimized to increase excitability of the sensorimotor network (SMN) while inducing cathodal inhibitory modulation over prefrontal and parietal brain regions negatively correlated with the SMN. Using an MRI-compatible multichannel transcranial electrical stimulation (tES) device, 20 healthy participants underwent real and sham tDCS while at rest in the MRI scanner. Changes in functional connectivity (FC) during and after stimulation were evaluated, looking at the intrinsic FC of the SMN and the strength of the negative connectivity between SMN and the rest of the brain. Standard, bifocal tDCS targeting left motor cortex (electrode ~C3) and right frontopolar (~Fp2) regions was tested as a control condition in a separate sample of healthy subjects to investigate network specificity of multichannel stimulation effects. Net-tDCS induced greater FC increase over the SMN compared to bifocal tDCS, during and after stimulation. Moreover, exploratory analysis of the impact of net-tDCS on negatively correlated networks showed an increase in the negative connectivity between SMN and prefrontal/parietal areas targeted by cathodal stimulation both during and after real net-tDCS. Results suggest preliminary evidence of the possibility of manipulating distributed network connectivity patterns through net-tDCS, with potential relevance for the development of cognitive enhancement and therapeutic tES solutions.