Frontoparietal Brain Network Plays a Crucial Role in Working Memory Capacity during Complex Cognitive Task.

Recent neurophysiological studies provide inconsistent results of frontoparietal network (FPN) stimulation for altering working memory (WM) capacity. This study aimed to boost WM capacity by manipulating the activity of the FPN via dual-site high-definition transcranial direct current stimulation. Forty-eight participants were randomly assigned to three stimulation groups, receiving either simultaneous anodal stimulation of the frontal and parietal areas (double stimulation), or stimulation of the frontal area only (single stimulation), or the placebo stimulation (sham) to frontal and parietal areas. After the stimulation, we used an operation span task to test memory accuracy, mathematical accuracy, time of calculation and memorizing, and recall response time across the three groups. The results revealed an enhancement of memory accuracy and a reduction of time of calculation in the double stimulation group compared with that in others. In addition, recall response time was significantly decreased in the double and single stimulation groups compared with that in sham. No differences in mathematical accuracy were observed. Our results confirm the pivotal role of the FPN in WM and suggest its functional dissociation, with the frontal component more implicated in the retrieval stage and the parietal component in the processing and retention stages.

Posterior parietal cortex is causally involved in reward valuation but not in probability weighting during risky choice.

This study provides evidence that the posterior parietal cortex is causally involved in risky decision making via the processing of reward values but not reward probabilities. In the within-group experimental design, participants performed a binary lottery choice task following transcranial magnetic stimulation of the right posterior parietal cortex, left posterior parietal cortex, and a right posterior parietal cortex sham (placebo) stimulation. The continuous theta-burst stimulation protocol supposedly downregulating the cortical excitability was used. Both, mean-variance and the prospect theory approach to risky choice showed that the posterior parietal cortex stimulation shifted participants toward greater risk aversion compared with sham. On the behavioral level, after the posterior parietal cortex stimulation, the likelihood of choosing a safer option became more sensitive to the difference in standard deviations between lotteries, compared with sham, indicating greater risk avoidance within the mean-variance framework. We also estimated the shift in prospect theory parameters of risk preferences after posterior parietal cortex stimulation. The hierarchical Bayesian approach showed moderate evidence for a credible change in risk aversion parameter toward lower marginal reward value (and, hence, lower risk tolerance), while no credible change in probability weighting was observed. In addition, we observed anecdotal evidence for a credible increase in the consistency of responses after the left posterior parietal cortex stimulation compared with sham.

Transcranial magnetic stimulation of the left middle frontal gyrus modulates the information people communicate in different social contexts.

Neocortical structures of the left frontal lobe, middle frontal gyrus (MFG) in particular, have been suggested to be linked to the processing of punishing and unpleasant outcomes in decision tasks. To assess the role of left MFG (lMFG) in communicative decisions, we used repetitive transcranial magnetic stimulation (rTMS) to inhibit its function during communicational exchanges under two types of social contexts: formal and informal. Three groups of participants received an offline 1-Hz inhibitory rTMS of lMFG, right MFG as an active control site, or lMFG sham/placebo TMS as a passive control condition. Participants' task included answering difficult general-knowledge questions, rating their confidence in their answers' correctness, and, finally, deciding if they would report or withhold these answers in formal and informal social contexts. There were significantly more reported than withheld answers in the informal context in all groups. The formal context showed no differences between reported and withheld answers in both control conditions, while, crucially, real rTMS of lMFG produced a different pattern, with more withheld than reported answers. Thus, lMFG inhibition seems to result in more rational decisions made only in formal communication contexts, where there is a perception of a certain pressure or possible negative outcomes. In informal social contexts and in the absence of negative consequences the pattern of answers did not change, regardless of the reporting strategy or the TMS protocol used. These results suggest selective context-dependent involvement of the lMFG in decision-making processes during communicational exchanges taking place under social pressure.

Repetitive transcranial magnetic stimulation modulates action naming over the left but not right inferior frontal gyrus.

fMRI language mapping studies report right-hemispheric contribution to language in healthy individuals. However, it remains unclear whether these right-hemispheric patterns of activity are critical for language, which is highly relevant for clinical preoperative language mapping. The available findings are controversial. In this study, we first measured individual patterns of language lateralization with an fMRI language localizer in healthy participants with different handedness (N = 31). Then, the same participants received rTMS over the individual coordinates of peak fMRI-based activation in the left and right inferior frontal gyri. During rTMS, participants performed a picture naming task. It included both objects and actions to test whether naming of nouns and verbs would be equally modulated by rTMS. Stimulation of the left inferior frontal gyrus resulted in accuracy facilitation of verb production regardless of individual language lateralization. No modulation of object naming was found at any stimulation site in terms of accuracy nor reaction time. This study causally confirmed the critical contribution of the left, but not the right hemisphere to verb production regardless of the language lateralization patterns observed with fMRI. Also, the results stress that action rather than object naming is the task of choice for mapping language in the frontal lobe.

Dorsolateral prefrontal cortex plays causal role in probability weighting during risky choice.

In this study, we provide causal evidence that the dorsolateral prefrontal cortex (DLPFC) supports the computation of subjective value in choices under risk via its involvement in probability weighting. Following offline continuous theta-burst transcranial magnetic stimulation (cTBS) of the DLPFC subjects (N = 30, mean age 23.6, 56% females) completed a computerized task consisting of 96 binary lottery choice questions presented in random order. Using the hierarchical Bayesian modeling approach, we then estimated the structural parameters of risk preferences (the degree of risk aversion and the curvature of the probability weighting function) and analyzed the obtained posterior distributions to determine the effect of stimulation on model parameters. On a behavioral level, temporary downregulation of the left DLPFC excitability through cTBS decreased the likelihood of choosing an option with higher expected reward while the probability of choosing a riskier lottery did not significantly change. Modeling the stimulation effects on risk preference parameters showed anecdotal evidence as assessed by Bayes factors that probability weighting parameter increased after the left DLPFC TMS compared to sham.

Noninvasive brain stimulation and brain oscillations.

Recent technological advances in the field of noninvasive brain stimulation (NIBS) have allowed to interact with endogenous brain oscillatory activity, the main neural communication code of our brain, opening new scenarios for transient modifications of cognitive and behavioral performances: such a possibility can be capitalized both for research purposes in healthy subjects, as well as in the context of therapeutic and rehabilitative settings. Among NiBS methodologies, transcranial magnetic stimulation (TMS) has been the first used to this purpose, and also thanks to the technical development of TMS-EEG co-registering systems, the mechanistic knowledge regarding the role of brain oscillations has been improved. Another approach to brain oscillations considers electric stimulation methods, such as transcranial direct current stimulation (tDCS), and especially transcranial alternating current stimulation (tACS), for which -however- some technical and conceptual caveats have emerged. In this chapter, we briefly review the uses of NiBS in this field up to now, by providing an update on the current status of research applications as well as of its attempts of exploitation in translational clinical applications, especially regarding motor disorders and for understanding and reducing some psychiatric symptoms.

Online and offline effects of transcranial alternating current stimulation of the primary motor cortex.

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that allows interaction with endogenous cortical oscillatory rhythms by means of external sinusoidal potentials. The physiological mechanisms underlying tACS effects are still under debate. Whereas online (e.g., ongoing) tACS over the motor cortex induces robust state-, phase- and frequency-dependent effects on cortical excitability, the offline effects (i.e. after-effects) of tACS are less clear. Here, we explored online and offline effects of tACS in two single-blind, sham-controlled experiments. In both experiments we used neuronavigated transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) as a probe to index changes of cortical excitability and delivered M1 tACS at 10 Hz (alpha), 20 Hz (beta) and sham (30 s of low-frequency transcranial random noise stimulation; tRNS). Corticospinal excitability was measured by single pulse TMS-induced motor evoked potentials (MEPs). tACS was delivered online in Experiment 1 and offline in Experiment 2. In Experiment 1, the increase of MEPs size was maximal with the 20 Hz stimulation, however in Experiment 2 neither the 10 Hz nor the 20 Hz stimulation induced tACS offline effects. These findings support the idea that tACS affects cortical excitability only during online application, at least when delivered on the scalp overlying M1, thereby contributing to the development of effective protocols that can be applied to clinical populations.

Impact of ß-range-induced oscillatory activity on human input-output relationship of the corticospinal pathway.

Objective: The aim of the study was to show that short-lasting (90 s) transcranial alternating current stimulation (tACS) at 20 Hz delivered over the left primary motor cortex (M1) is able to change the shape of recruitment curve of the corticospinal pathway.Methods: The corticospinal pathway was studied during tACS by means of the relationship between the intensity of transcranial magnetic stimulation (TMS) delivered over the left M1 and corresponding motor evoked potentials (MEPs) recorded from the right first dorsal interosseus muscle (FDI), in nine healthy subjects. In order to extract characteristics of the input-output relationship that have particular physiological relevance, data were fitted to the Boltzmann sigmoidal function by the Levenberg-Marquardt nonlinear, least mean squares algorithm.Results: The ß-rhythm tACS influenced the shape and parameters of the input-output relation, so that the initial segment of the conditioned curve (from threshold to 30% of maximum muscle size) diverged, while the subsequent segment converged to overlap the unconditioned control curve.Discussion: ß-rhythm tACS conditions only a definite subset of corticospinal elements influencing less than 30% of the entire motoneuronal pool. The fact that ß-rhythm tACS mainly affects the most excitable motoneurons could explain the observed antikinetic effect of the tACS at ß-rhythm applied in the motor regions.

Examining the effects of transcranial direct current stimulation on human episodic memory with machine learning.

We aimed to replicate a published effect of transcranial direct-current stimulation (tDCS)-induced recognition enhancement over the human ventrolateral prefrontal cortex (VLPFC) and analyse the data with machine learning. We investigated effects over an adjacent region, the dorsolateral prefrontal cortex (DLPFC). In total, we analyzed data from 97 participants after exclusions. We found weak or absent effects over the VLPFC and DLPFC. We conducted machine learning studies to examine the effects of semantic and phonetic features on memorization, which revealed no effect of VLPFC tDCS on the original dataset or the current data. The highest contributing factor to memory performance was individual differences in memory not explained by word features, tDCS group, or sample size, while semantic, phonetic, and orthographic word characteristics did not contribute significantly. To our knowledge, this is the first tDCS study to investigate cognitive effects with machine learning, and future studies may benefit from studying physiological as well as cognitive effects with data-driven approaches and computational models.

Author Correction: State-Dependent Effects of Transcranial Oscillatory Currents on the Motor System during Action Observation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

State-Dependent Effects of Transcranial Oscillatory Currents on the Motor System during Action Observation.

We applied transcranial alternating current stimulation (tACS) to the primary motor cortex (M1) at different frequencies during an index-thumb pinch-grip observation task. To estimate changes in the corticospinal output, we used the size of motor evoked potentials (MEPs) obtained by transcranial magnetic stimulation (TMS) of M1 using an online MRI-guided simultaneous TMS-tACS approach. The results of the beta-tACS confirm a non-selective increase in corticospinal excitability in subjects at rest; an increase was observed for both of the tested hand muscles, the first dorsal interosseous (FDI) and the abductor digiti minimi (ADM). However, during action observation of the pinch-grip movement, the increase of corticospinal excitability was only observed for the prime mover FDI muscle and took place during alpha-tACS, while gamma-tACS affected both the FDI and control muscle (ADM) responses. These phenomena likely reflect the hypothesis that the mu and gamma rhythms specifically index the downstream modulation of primary sensorimotor areas by engaging mirror neuron activity. The current neuromodulation approach confirms that tACS can be used to induce neurophysiologically detectable state-dependent enhancement effects, even in complex motor-cognitive tasks.

Transcranial Direct Current Stimulation Effects on Memory Consolidation: Timing Matters.

Transcranial direct current stimulation (tDCS) is a promising tool for modulation of learning and memory, allowing to transiently change cortical excitability of specific brain regions with physiological and behavioral outcomes. A detailed exploration of factors that can moderate tDCS effects on episodic long-term memory (LTM) is of high interest due to the clinical potential for patients with traumatic or pathological memory deficits and with cognitive impairments. This commentary discusses findings by Marián et al. (2018) recently published in Cortex within a broad context of brain stimulation in memory research.

A systematic review and meta-analysis of the effects of transcranial direct current stimulation (tDCS) on episodic memory.

BACKGROUND: In the past decade, several studies have examined the effects of transcranial direct current stimulation (tDCS) on long-term episodic memory formation and retrieval. These studies yielded conflicting results, likely due to differences in stimulation parameters, experimental design and outcome measures. OBJECTIVES: In this work we aimed to assess the robustness of tDCS effects on long-term episodic memory using a meta-analytical approach. METHODS: We conducted four meta-analyses to analyse the effects of anodal and cathodal tDCS on memory accuracy and response times. We also used a moderator analysis to examine whether the size of tDCS effects varied as a function of specific stimulation parameters and experimental conditions. RESULTS: Although all selected studies reported a significant effect of tDCS in at least one condition in the published paper, the results of the four meta-analyses showed only statistically non-significant close-to-zero effects. A moderator analysis suggested that for anodal tDCS, the duration of the stimulation and the task used to probe memory moderated the effectiveness of tDCS. For cathodal tDCS, site of stimulation was a significant moderator, although this result was based on only a few observations. CONCLUSIONS: To warrant theoretical advancement and practical implications, more rigorous research is needed to fully understand whether tDCS reliably modulates episodic memory, and the specific circumstances under which this modulation does, and does not, occur.

No Effect of the Right Posterior Parietal Cortex tDCS in Dual-Target Visual Search.

"Subsequent search misses" represent a decrease in accuracy at detecting a second target in a visual search task. In this study, we tested the possibility to modulate this effect via inhibition of the right posterior parietal cortex trough transcranial direct current stimulation (tDCS). The target stimuli were T-shapes presented among L-shaped distractors. The participant's task was to detect targets or to report their absence. For each trial, targets could be represented by one high-salient target, one low-salient target, two different targets (one high salient and one low salient), two high salient targets, two low salient targets, or no targets at all (catch-trials). Offline tDCS was applied over the right (target site) or left (control site) posterior parietal cortex. Sham stimulation over the right posterior parietal cortex was included as a control (placebo). Stimulation lasted for 10 min. Afterward, participants were asked to perform the experiment. Our findings suggest that stimulation did not modulate any of the task conditions, suggesting potential limitation of the study: either tDCS was not enough powerful to modulate the task performance or the task was too easy to be modulated by stimulation.

Midfrontal theta transcranial alternating current stimulation modulates behavioural adjustment after error execution.

Cognitive control during conflict monitoring, error processing, and post-error adjustment appear to be associated with the occurrence of midfrontal theta (MFÏ´). While this association is supported by correlational EEG studies, much less is known about the possible causal link between MFÏ´ and error and conflict processing. In the present study, we aimed to explore the role of band-specific effects in modulating the error system during a conflict resolution. In turn, we delivered transcranial alternating current stimulation (tACS) at different frequency bands (delta δ, theta θ, alpha α, beta ß, gamma γ) and sham stimulation over the medial frontal cortex (MFC) in 36 healthy participants performing a modified version of the Flanker task. Task performance and reports about the sensations (e.g. visual flickering, cutaneous burning) induced by the different frequency bands, were also recorded. We found that online θ-tACS increased the response speed to congruent stimuli after error execution with respect to sham stimulation. Importantly, the accuracy following the errors did not decrease because of speed-accuracy trade off. Moreover, tACS evoked visual and somatosensory sensations were significantly stronger at α-tACS and ß-tACS compared to other frequencies. Our findings suggest that theta activity plays a causative role in modulating behavioural adjustments during perceptual choices in a stimulus-response conflict task.

Modulating the interhemispheric balance in healthy participants with transcranial direct current stimulation: No significant effects on word or sentence processing.

Patient studies and brain stimulation evidence suggest that language processing can be enhanced by altering the interhemispheric balance: namely, preferentially enhancing left-hemisphere activity while suppressing right-hemisphere activity. To our knowledge, no study has yet compared the effects of such bilateral brain stimulation to both logically necessary control conditions (separate left- and right-hemisphere stimulation). This study did so in a between-group sham-controlled design, applying transcranial direct current stimulation over Broca's area and/or its homologue in 72 healthy participants. The effects were measured not only in a single-word-level task but also in a sentence-level task, rarely tested previously. We did not find either any significant overall effects of stimulation or greater stimulation effects in the bilateral compared to control groups. This null result, obtained in a large sample, contributes to the debate on whether tDCS can modulate language processing in healthy individuals.

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation.

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Dynamic changes in prefrontal cortex involvement during verbal episodic memory formation.

During encoding, the neural activity immediately before or during an event can predict whether that event will be later remembered. The contribution of brain activity immediately after an event to memory formation is however less known. Here, we used repetitive Transcranial Magnetic Stimulation (rTMS) to investigate the temporal dynamics of episodic memory encoding with a focus on post-stimulus time intervals. At encoding, rTMS was applied during the online processing of the word, at its offset, or 100, 200, 300 or 400ms thereafter. rTMS was delivered to the left ventrolateral (VLPFC) or dorsolateral prefrontal cortex (DLPFC). VLPFC rTMS during the first few hundreds of milliseconds after word offset disrupted subsequent recognition accuracy. We did not observe effects of DLPFC rTMS at any time point. These results suggest that encoding-related VLPFC engagement starts at a relatively late processing stage, and may reflect brain processes related to the offset of the stimulus.