Increasing mind wandering with accelerated intermittent theta burst stimulation over the left dorsolateral prefrontal cortex.

Mind wandering (MW) is the intentional or unintentional experience of attending to internal task-unrelated thoughts while being occupied with an external task. Even though maintaining task focus is assumed to require executive functions (EF), it is not clear how and to what extent MW and EF interact. Research has found that activity in the dorsolateral prefrontal cortex (DLPFC) is associated with EF and MW. To understand the causal role of the DLPFC in relation to MW and EF, researchers have turned to non-invasive brain stimulation. Thus far, most studies have used transcranial direct current stimulation, but the results have been inconclusive. To further elucidate the relationship between the DLPFC, EF and MW, we conducted a pre-registered, sham-controlled, triple-blinded within-subject experiment by combining intermittent theta burst stimulation (iTBS) interleaved with a recently developed MW-EF task. In contrast to our expectations, participants reported significantly more MW following real iTBS as compared to sham stimulation. However, at the same time, psychomotor precision and EF improved, indicating that participants were able to engage in resource-intensive MW while simultaneously performing well on the task. We argue that iTBS enhanced the underlying executive resources that could be used to increase both MW and task performance in line with the resource-control view of MW. This finding opens exciting avenues for studying the complex interplay between MW and EF and provides empirical support for the utility of iTBS in improving executive performance during a demanding cognitive task.

A high-resolution 7 Tesla resting-state fMRI dataset optimized for studying the subcortex.

To achieve a comprehensive understanding of spontaneous brain dynamics in humans, in vivo acquisition of intrinsic activity across both cortical and subcortical regions is necessary. Here we present advanced whole-brain, resting-state functional magnetic resonance imaging (rs-fMRI) data acquired at 7 Tesla with 1.5 mm isotropic voxel resolution. Functional images were obtained from 56 healthy adults (33 females, ages 19-39 years) in two runs of 15 min eyes-open wakeful rest. The high spatial resolution and short echo times of the multiband echo-planar imaging (EPI) protocol optimizes blood oxygen level-dependent (BOLD)-sensitivity for the subcortex while concurrent respiratory and cardiac measures enable retrospective correction of physiological noise, resulting in data that is highly suitable for researchers interested in subcortical BOLD signal. Functional timeseries were coregistered to high-resolution T1-weighted structural data (0.75 mm isotropic voxels) acquired during the same scanning session. To accommodate data reutilization, functional and structural images were formatted to the Brain Imaging Data Structure (BIDS) and preprocessed with fMRIPrep.

Testing Sexual Strategy Theory in Norway.

Choosing a romantic partner for a long-term relationship is one of the most significant decisions one makes during our lifetime. We have inherited an evolved framework from our ancestors that contains traits, as well as preferences for these traits, to solve this task. We use this framework consciously or unconsciously to choose prospective romantic partners. Following this reasoning, sexual strategy theory (SST) has been proposed for predicting which traits women and men prefer in a romantic partner for a long-term relationship. These predictions were empirically tested in the current work based on a sample of 1193 Norwegian adolescents who responded to an online questionnaire. We implemented the study hypotheses, derived from SST, in three statistical models, which were tested using structural equation modeling. In brief, our results revealed that women only valued resources more than men when we controlled for materialistic traits. This finding contrasts with SST's prediction that women would value resources more than men, independently of other variables. As for the second prediction that men value physical attractiveness more than women, this pattern existed universally and was independent of, for instance, how egalitarian they were. We thus conclude that SST was only partially supported and that variables that may reflect societal circumstances (e.g., wealth, gender, equality) should be considered when examining the mate choice behavior of women and men. The theoretical and practical implications of the study are also discussed.

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial.

BACKGROUND: Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response. METHODS: In this trial, outpatients (N = 96, aged 22-65 years) meeting the diagnostic criteria for at least moderate depression (Montgomery and Aasberg Depression Rating Scale score ≥ 20) will be enrolled prospectively and receive ten, once-a-day sessions of either active iTBS or sham iTBS to the left DLPFC, localized via a neuronavigation system. Participants may have any degree of treatment resistance. Prior to stimulation, participants will undergo a thorough safety screening and a brief diagnostic assessment, genetic analysis of brain-derived neurotropic factor, 5-HTTLPR and 5-HT1A, and cerebral MRI assessments. A selection of neuropsychological tests and questionnaires will be administered prior to stimulation and after ten stimulations. An additional follow-up will be conducted 4 weeks after the last stimulation. The first participant was enrolled on June 4, 2022. Study completion will be in December 2027. The project is approved by the Regional Ethical Committee of Medicine and Health Sciences, Northern Norway, project number 228765. The trial will be conducted according to Good Clinical Practice and published safety guidelines on rTMS treatment. DISCUSSION: The aims of the present trial are to investigate the antidepressive effect of a 10-session iTBS protocol on moderately depressed outpatients and to explore the factors that can explain the reduction in depressive symptoms after iTBS but also a poorer response to the treatment. In separate, but related work packages, the trial will assess how clinical, cognitive, brain imaging and genetic measures at baseline relate to the variability in the antidepressive effects of iTBS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05516095. Retrospectively registered on August 25, 2022.

Echoes from Intrinsic Connectivity Networks in the Subcortex.

Decades of research have greatly improved our understanding of intrinsic human brain organization in terms of functional networks and the transmodal hubs within the cortex at which they converge. However, substrates of multinetwork integration in the human subcortex are relatively uncharted. Here, we leveraged recent advances in subcortical atlasing and ultra-high field (7 T) imaging optimized for the subcortex to investigate the functional architecture of 14 individual structures in healthy adult males and females with a fully data-driven approach. We revealed that spontaneous neural activity in subcortical regions can be decomposed into multiple independent subsignals that correlate with, or "echo," the activity in functional networks across the cortex. Distinct subregions of the thalamus, striatum, claustrum, and hippocampus showed a varied pattern of echoes from attention, control, visual, somatomotor, and default mode networks, demonstrating evidence for a heterogeneous organization supportive of functional integration. Multiple network activity furthermore converged within the globus pallidus externa, substantia nigra, and ventral tegmental area but was specific to one subregion, while the amygdala and pedunculopontine nucleus preferentially affiliated with a single network, showing a more homogeneous topography. Subregional connectivity of the globus pallidus interna, subthalamic nucleus, red nucleus, periaqueductal gray, and locus coeruleus did not resemble patterns of cortical network activity. Together, these finding describe potential mechanisms through which the subcortex participates in integrated and segregated information processing and shapes the spontaneous cognitive dynamics during rest.SIGNIFICANCE STATEMENT Despite the impact of subcortical dysfunction on brain health and cognition, large-scale functional mapping of subcortical structures severely lags behind that of the cortex. Recent developments in subcortical atlasing and imaging at ultra-high field provide new avenues for studying the intricate functional architecture of the human subcortex. With a fully data-driven analysis, we reveal subregional connectivity profiles of a large set of noncortical structures, including those rarely studied in fMRI research. The results have implications for understanding how the functional organization of the subcortex facilitates integrative processing through cross-network information convergence, paving the way for future work aimed at improving our knowledge of subcortical contributions to intrinsic brain dynamics and spontaneous cognition.

Transcranial direct-current stimulation enhances Pavlovian tendencies during intermittent loss of control.

Introduction: Pavlovian bias is an innate motivational tendency to approach rewards and remain passive in the face of punishment. The relative reliance on Pavlovian valuation has been found to increase when the perceived control over environmental reinforcers is compromised, leading to behavior resembling learned helplessness (LH). Methods: Sixty healthy young adults underwent a Go-NoGo reinforcement learning task and received anodal high-definition transcranial direct current stimulation (HD-tDCS) over the medial prefrontal/dorsal anterior cingulate cortex in our randomized, double-blind, sham- controlled study. Furthermore, we evaluated changes in cue-locked mid-frontal theta power derived from simultaneous electroencephalography (EEG). We hypothesized that active stimulation would reduce Pavlovian bias during manipulation of outcome controllability, and the effect would be accompanied by stronger mid-frontal theta activity, representing arbitration between choice strategies in favor of instrumental relative to Pavlovian valuation. Results: We found a progressive decrease in Pavlovian bias during and after loss of control over feedback. Active HD-tDCS counteracted this effect while not affecting the mid-frontal theta signal. Discussion: The results were at odds with our hypotheses but also with previous findings reporting LH-like patterns during and after loss of control without brain stimulation. The discrepancy may be related to different protocols for the controllability manipulation. We argue that the subjective evaluation of task controllability is crucial in mediating the balance between Pavlovian and instrumental valuation during reinforcement learning and that the medial prefrontal/dorsal anterior cingulate cortex is a key region in this respect. These findings have implications for understanding the behavioral and neural underpinnings of LH in humans.

Aberrant uncertainty processing is linked to psychotic-like experiences, autistic traits, and is reflected in pupil dilation during probabilistic learning.

Aberrant belief updating due to misestimation of uncertainty and an increased perception of the world as volatile (i.e., unstable) has been found in autism and psychotic disorders. Pupil dilation tracks events that warrant belief updating, likely reflecting the adjustment of neural gain. However, whether subclinical autistic or psychotic symptoms affect this adjustment and how they relate to learning in volatile environments remains to be unraveled. We investigated the relationship between behavioral and pupillometric markers of subjective volatility (i.e., experience of the world as unstable), autistic traits, and psychotic-like experiences in 52 neurotypical adults with a probabilistic reversal learning task. Computational modeling revealed that participants with higher psychotic-like experience scores overestimated volatility in low-volatile task periods. This was not the case for participants scoring high on autistic-like traits, who instead showed a diminished adaptation of choice-switching behavior in response to risk. Pupillometric data indicated that individuals with higher autistic- or psychotic-like trait and experience scores differentiated less between events that warrant belief updating and those that do not when volatility was high. These findings are in line with misestimation of uncertainty accounts of psychosis and autism spectrum disorders and indicate that aberrancies are already present at the subclinical level.

Modulation of mind wandering using transcranial direct current stimulation: A meta-analysis based on electric field modeling.

Mind wandering (MW) is a heterogeneous construct involving task-unrelated thoughts. Recently, the interest in modulating MW propensity via non-invasive brain stimulation techniques has increased. Single-session transcranial direct current stimulation (tDCS) in healthy controls has led to mixed results in modulating MW propensity, possibly due to methodological heterogeneity. Therefore, our aim was to conduct a systematic meta-analysis to examine the influence of left dorsolateral prefrontal cortex (lDLPFC) and right inferior parietal lobule (rIPL) targeted tDCS on MW propensity. Importantly, by computational modeling of tDCS-induced electric fields, we accounted for differences in tDCS-dose across studies that varied strongly in their applied methodology. Fifteen single-session, sham-controlled tDCS studies published until October 2021 were included. All studies involved healthy adult participants and used cognitive tasks combined with MW thought-probes. Heterogeneity in tDCS electrode placement, stimulation polarity and intensity were controlled for by means of electric field simulations, while overall methodological quality was assessed via an extended risk of bias (RoB) assessment. We found that RoB was the strongest predictor of study outcomes. Moreover, the rIPL was the most promising cortical area for influencing MW, with stronger anodal electric fields in this region being negatively associated with MW propensity. Electric field strength in the lDLPFC was not related to MW propensity. We identified several severe methodological problems that could have contributed to overestimated effect sizes in this literature, an issue that needs urgent attention in future research in this area. Overall, there is no reliable evidence for tDCS influencing MW in the healthy. However, the analysis also revealed that increasing neural excitability in the rIPL via tDCS might be associated with reduced MW propensity. In an exploratory approach, we also found some indication that targeting prefrontal regions outside the lDLPFC with tDCS could lead to increased MW propensity.

Self-reported mind wandering reflects executive control and selective attention.

Mind wandering is ubiquitous in everyday life and has a pervasive and profound impact on task-related performance. A range of psychological processes have been proposed to underlie these performance-related decrements, including failures of executive control, volatile information processing, and shortcomings in selective attention to critical task-relevant stimuli. Despite progress in the development of such theories, existing descriptive analyses have limited capacity to discriminate between the theories. We propose a cognitive-model based analysis that simultaneously explains self-reported mind wandering and task performance. We quantitatively compare six explanations of poor performance in the presence of mind wandering. The competing theories are distinguished by whether there is an impact on executive control and, if so, how executive control acts on information processing, and whether there is an impact on volatility of information processing. Across two experiments using the sustained attention to response task, we find quantitative evidence that mind wandering is associated with two latent factors. Our strongest conclusion is that executive control is impaired: increased mind wandering is associated with reduced ability to inhibit habitual response tendencies. Our nuanced conclusion is that executive control deficits manifest in reduced ability to selectively attend to the information value of rare but task-critical events.

Mind-wandering: mechanistic insights from lesion, tDCS, and iEEG.

Cognitive neuroscience has witnessed a surge of interest in investigating the neural correlates of the mind when it drifts away from an ongoing task and the external environment. To that end, functional neuroimaging research has consistently implicated the default mode network (DMN) and frontoparietal control network (FPCN) in mind-wandering. Yet, it remains unknown which subregions within these networks are necessary and how they facilitate mind-wandering. In this review, we synthesize evidence from lesion, transcranial direct current stimulation (tDCS), and intracranial electroencephalogram (iEEG) studies demonstrating the causal relevance of brain regions, and providing insights into the neuronal mechanism underlying mind-wandering. We propose that the integration of complementary approaches is the optimal strategy to establish a comprehensive understanding of the neural basis of mind-wandering.

Catching wandering minds with tapping fingers: neural and behavioral insights into task-unrelated cognition.

When the human mind wanders, it engages in episodes during which attention is focused on self-generated thoughts rather than on external task demands. Although the sustained attention to response task is commonly used to examine relationships between mind wandering and executive functions, limited executive resources are required for optimal task performance. In the current study, we aimed to investigate the relationship between mind wandering and executive functions more closely by employing a recently developed finger-tapping task to monitor fluctuations in attention and executive control through task performance and periodical experience sampling during concurrent functional magnetic resonance imaging (fMRI) and pupillometry. Our results show that mind wandering was preceded by increases in finger-tapping variability, which was correlated with activity in dorsal and ventral attention networks. The entropy of random finger-tapping sequences was related to activity in frontoparietal regions associated with executive control, demonstrating the suitability of this paradigm for studying executive functioning. The neural correlates of behavioral performance, pupillary dynamics, and self-reported attentional state diverged, thus indicating a dissociation between direct and indirect markers of mind wandering. Together, the investigation of these relationships at both the behavioral and neural level provided novel insights into the identification of underlying mechanisms of mind wandering.

Transcranial Direct Current Stimulation above the Medial Prefrontal Cortex Facilitates Decision-Making following Periods of Low Outcome Controllability.

Recent studies suggest that choice behavior in reinforcement learning tasks is shaped by the level of outcome controllability. In particular, Pavlovian bias (PB) seems to be enhanced under low levels of control, manifesting in approach tendencies toward rewards and response inhibition when facing potential losses. The medial prefrontal cortex (mPFC) has been implicated both in evaluating outcome controllability and in the recruitment of cognitive control (CC) to suppress maladaptive PB during reinforcement learning. The current study tested whether high-definition transcranial direct current stimulation (HD-tDCS) above the mPFC of healthy humans can influence PB, and counteract the previously documented, deleterious behavioral effects of low outcome controllability on decision-making. In a preregistered, between-group, double-blind study (N = 103 adults, both sexes), we tested the interaction between controllability and HD-tDCS on parameters of choice behavior in a Go/NoGo task. Relative to sham stimulation, HD-tDCS resulted in more robust performance improvement following reduced control, an effect that was more pronounced in appetitive trials. In addition, we found evidence for weaker PB when HD-tDCS was administered during low controllability over outcomes. Computational modeling revealed that parameter estimates of learning rate and choice randomness were modulated by controllability, HD-tDCS and their interaction. Overall, these results highlight the potential of our HD-tDCS protocol for interfering with choice arbitration under low levels of control, resulting in more adaptive behavior.

High-Definition Transcranial Direct Current Stimulation Improves Delayed Memory in Alzheimer's Disease Patients: A Pilot Study Using Computational Modeling to Optimize Electrode Position.

BACKGROUND: The optimal stimulation parameters when using transcranial direct current stimulation (tDCS) to improve memory performance in patients with Alzheimer's disease (AD) are lacking. In healthy individuals, inter-individual differences in brain anatomy significantly influence current distribution during tDCS, an effect that might be aggravated by variations in cortical atrophy in AD patients. OBJECTIVE: To measure the effect of individualized HD-tDCS in AD patients. METHODS: Nineteen AD patients were randomly assigned to receive active or sham high-definition tDCS (HD-tDCS). Computational modeling of the HD-tDCS-induced electric field in each patient's brain was analyzed based on magnetic resonance imaging (MRI) scans. The chosen montage provided the highest net anodal electric field in the left dorsolateral prefrontal cortex (DLPFC). An accelerated HD-tDCS design was conducted (2 mA for 3×20 min) on two separate days. Pre- and post-intervention cognitive tests and T1 and T2-weighted MRI and diffusion tensor imaging data at baseline were analyzed. RESULTS: Different montages were optimal for individual patients. The active HD-tDCS group improved significantly in delayed memory and MMSE performance compared to the sham group. Five participants in the active group had higher scores on delayed memory post HD-tDCS, four remained stable and one declined. The active HD-tDCS group had a significant positive correlation between fractional anisotropy in the anterior thalamic radiation and delayed memory score. CONCLUSION: HD-tDCS significantly improved delayed memory in AD. Our study can be regarded as a proof-of-concept attempt to increase tDCS efficacy. The present findings should be confirmed in larger samples.

Short-lived Alpha Power Suppression Induced by Low-intensity Arrhythmic rTMS.

This study was conducted to provide a better understanding of the role of electric field strength in the production of aftereffects in resting state scalp electroencephalography by repetitive transcranial magnetic stimulation (rTMS) in humans. We conducted two separate experiments in which we applied rTMS over the left parietal-occipital region. Prospective electric field simulation guided the choice of the individual stimulation intensities. In the main experiment, 16 participants received rhythmic and arrhythmic rTMS bursts at between ca. 20 and 50 mv/mm peak absolute electric field intensities. In the control experiment, another group of 16 participants received sham rTMS. To characterize the aftereffects, we estimated the alpha power (8-14 Hz) changes recorded in the inter-burst intervals, i.e., from 0.2 to 10 s after rTMS. We found aftereffects lasting up to two seconds after stimulation with ca. 35 mV/mm. Relative to baseline, alpha power was significantly reduced by the arrhythmic protocol, while there was no significant change with the rhythmic protocol. We found no significant long-term, i.e., up to 10-second, differences between the rhythmic and arrhythmic stimulation, or between the rhythmic and sham protocols. Weak arrhythmic rTMS induced short-lived alpha suppression during the inter-burst intervals.

Selecting stimulation intensity in repetitive transcranial magnetic stimulation studies: A systematic review between 1991 and 2020.

Repetitive transcranial magnetic stimulation (rTMS) is an increasingly used, non-invasive brain stimulation technique in neuroscience research and clinical practice with a broad spectrum of suggested applications. Among other parameters, the choice of stimulus intensity and intracranial electric field strength substantially impacts rTMS outcome. This review provides a systematic overview of the intensity selection approaches and stimulation intensities used in human rTMS studies. We also examined whether studies report sufficient information to reproduce stimulus intensities for basic science research models. We performed a systematic review by focusing on original studies published between 1991 and 2020. We included conventional (e.g., 1 or 10 Hz) and patterned protocols (e.g., continuous or intermittent theta burst stimulation). We identified 3,784 articles in total, and we manually processed a representative portion (20%) of randomly selected articles. The majority of the analyzed studies (90% of entries) used the motor threshold (MT) approach and stimulation intensities from 80% to 120% of the MT. For continuous and intermittent theta burst stimulation, the most frequent stimulation intensity was 80% of the active MT. Most studies (92% of entries) did not report sufficient information to reproduce the stimulation intensity. Only a minority of studies (1.03% of entries) estimated the rTMS-induced electric field strengths. We formulate easy-to-follow recommendations to help scientists and clinicians report relevant information on stimulation intensity. Future standardized reporting guidelines may facilitate the use of basic science approaches aiming at better understanding the molecular, cellular, and neuronal mechanisms of rTMS.

Overestimation of volatility in schizophrenia and autism? A comparative study using a probabilistic reasoning task.

BACKGROUND AND OBJECTIVES: A plethora of studies has investigated and compared social cognition in autism and schizophrenia ever since both conditions were first described in conjunction more than a century ago. Recent computational theories have proposed similar mechanistic explanations for various symptoms beyond social cognition. They are grounded in the idea of a general misestimation of uncertainty but so far, almost no studies have directly compared both conditions regarding uncertainty processing. The current study aimed to do so with a particular focus on estimation of volatility, i.e. the probability for the environment to change. METHODS: A probabilistic decision-making task and a visual working (meta-)memory task were administered to a sample of 86 participants (19 with a diagnosis of high-functioning autism, 21 with a diagnosis of schizophrenia, and 46 neurotypically developing individuals). RESULTS: While persons with schizophrenia showed lower visual working memory accuracy than neurotypical individuals, no significant group differences were found for metamemory or any of the probabilistic decision-making task variables. Nevertheless, exploratory analyses suggest that there may be an overestimation of volatility in subgroups of participants with autism and schizophrenia. Correlations revealed relationships between different variables reflecting (mis)estimation of uncertainty, visual working memory accuracy and metamemory. LIMITATIONS: Limitations include the comparably small sample sizes of the autism and the schizophrenia group as well as the lack of cognitive ability and clinical symptom measures. CONCLUSIONS: The results of the current study provide partial support for the notion of a general uncertainty misestimation account of autism and schizophrenia.

Probing the neural signature of mind wandering with simultaneous fMRI-EEG and pupillometry.

Mind wandering reflects the shift in attentional focus from task-related cognition driven by external stimuli toward self-generated and internally-oriented thought processes. Although such task-unrelated thoughts (TUTs) are pervasive and detrimental to task performance, their underlying neural mechanisms are only modestly understood. To investigate TUTs with high spatial and temporal precision, we simultaneously measured fMRI, EEG, and pupillometry in healthy adults while they performed a sustained attention task with experience sampling probes. Features of interest were extracted from each modality at the single-trial level and fed to a support vector machine that was trained on the probe responses. Compared to task-focused attention, the neural signature of TUTs was characterized by weaker activity in the default mode network but elevated activity in its anticorrelated network, stronger functional coupling between these networks, widespread increase in alpha, theta, delta, but not beta, frequency power, predominantly reduced amplitudes of late, but not early, event-related potentials, and larger baseline pupil size. Particularly, information contained in dynamic interactions between large-scale cortical networks was predictive of transient changes in attentional focus above other modalities. Together, our results provide insight into the spatiotemporal dynamics of TUTs and the neural markers that may facilitate their detection.

The interplay between executive control, behavioural variability and mind wandering: Insights from a high-definition transcranial direct-current stimulation study.

While the involvement of executive processes in mind wandering is largely undebated, their exact relationship is subject to an ongoing debate and rarely studied dynamically within-subject. Several brain-stimulation studies using transcranial direct current stimulation (tDCS) have attempted to modulate mind-wandering propensity by stimulating the left dorsolateral prefrontal cortex (DLPFC) which is an important hub in the prefrontal control network. In a series of three studies testing a total of N = 100 participants, we develop a novel task that allows to study the dynamic interplay of mind wandering, behavioural varibility and the flexible recruitment of executive resources as indexed by the randomness (entropy) of movement sequences generated by our participants. We consistently find that behavioural variability is increased and randomness is decreased during periods of mind wandering. Interestingly, we also find that behavioural variability interacts with the entropy-MW effect, opening up the possibility to detect distinct states of off-focus cognition. When applying a high-definition transcranial direct-current stimulation (HD-tDCS) montage to the left DLPFC, we find that propensity to mind wander is reduced relative to a group receiving sham stimulation.

θ-γ Cross-Frequency Transcranial Alternating Current Stimulation over the Trough Impairs Cognitive Control.

Cognitive control is a mental process, which underlies adaptive goal-directed decisions. Previous studies have linked cognitive control to electrophysiological fluctuations in the θ band and θ-γ cross-frequency coupling (CFC) arising from the cingulate and frontal cortices. However, to date, the behavioral consequences of different forms of θ-γ CFC remain elusive. Here, we studied the behavioral effects of the θ-γ CFC via transcranial alternating current stimulation (tACS) designed to stimulate the frontal and cingulate cortices in humans. Using a double-blind, randomized, repeated measures study design, 24 healthy participants were subjected to three active and one control CFC-tACS conditions. In the active conditions, 80-Hz γ tACS was coupled to 4-Hz θ tACS. Specifically, in two of the active conditions, short γ bursts were coupled to the delivered θ cycle to coincide with either its peaks or troughs. In the third active condition, the phase of a θ cycle modulated the amplitude of the γ oscillation. In the fourth, control protocol, 80-Hz tACS was continuously superimposed over the 4-Hz tACS, therefore lacking any phase specificity in the CFC. During the 20 min of stimulation, the participants performed a Go/NoGo monetary reward-based and punishment-based instrumental learning task. A Bayesian hierarchical logistic regression analysis revealed that relative to the control, the peak-coupled tACS had no effects on the behavioral performance, whereas the trough-coupled tACS and, to a lesser extent, amplitude-modulated tACS reduced performance in conflicting trials. Our results suggest that cognitive control depends on the phase specificity of the θ-γ CFC.

Weak rTMS-induced electric fields produce neural entrainment in humans.

Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modulating endogenous oscillations in humans. The current standard method for rTMS defines the stimulation intensity based on the evoked liminal response in the visual or motor system (e.g., resting motor threshold). The key limitation of the current approach is that the magnitude of the resulting electric field remains elusive. A better characterization of the electric field strength induced by a given rTMS protocol is necessary in order to improve the understanding of the neural mechanisms of rTMS. In this study we used a novel approach, in which individualized prospective computational modeling of the induced electric field guided the choice of stimulation intensity. We consistently found that rhythmic rTMS protocols increased neural synchronization in the posterior alpha frequency band when measured simultaneously with scalp electroencephalography. We observed this effect already at electric field strengths of roughly half the lowest conventional field strength, which is 80% of the resting motor threshold. We conclude that rTMS can induce immediate electrophysiological effects at much weaker electric field strengths than previously thought.