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.

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.

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.

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.

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.

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.

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.

Intermittent Absence of Control during Reinforcement Learning Interferes with Pavlovian Bias in Action Selection.

The ability to control the occurrence of rewarding and punishing events is crucial for our well-being. Two ways to optimize performance are to follow heuristics like Pavlovian biases to approach reward and avoid loss or to rely more on slowly accumulated stimulus-action associations. Although reduced control over outcomes has been linked to suboptimal decision-making in clinical conditions associated with learned helplessness, it is unclear how uncontrollability of the environment is related to the arbitration between different response strategies. This study directly tested whether a behavioral manipulation designed to induce learned helplessness in healthy adults (intermittent loss of control over feedback in a reinforcement learning task; "yoking") would modulate the magnitude of Pavlovian bias and the neurophysiological signature of cognitive control (frontal midline theta power) in healthy adults. Using statistical analysis and computational modeling of behavioral data and electroencephalographic signals, we found stronger Pavlovian influences and alterations in frontal theta activity in the yoked group. However, these effects were not accompanied by reduced performance in experimental blocks with regained control, indicating that our behavioral manipulation was not potent enough for inducing helplessness and impaired coping ability with task demands. We conclude that the level of contingency between instrumental choices and rewards/punishments modulates Pavlovian bias during value-based decision-making, probably via interfering with the implementation of cognitive control. These findings might have implications for understanding the mechanisms underlying helplessness in various psychiatric conditions.

Increasing propensity to mind-wander by transcranial direct current stimulation? A registered report.

Transcranial direct current stimulation (tDCS) has been proposed to be able to modulate different cognitive functions. However, recent meta-analyses conclude that its efficacy is still in question. Recently, an increase in subjects' propensity to mind-wander has been reported as a consequence of anodal stimulation of the left dorsolateral prefrontal cortex (Axelrod et al., Proceedings of the National Academy of Sciences of the United States of America, 112, 2015). In addition, an independent group found a decrease in mind wandering after cathodal stimulation of the same region. These findings seem to indicate that high-level cognitive processes such as mind wandering can reliably be influenced by non-invasive brain stimulation. However, these previous studies used low sample sizes and are as such subject to concerns regarding the replicability of their findings. In this registered report, we implement a high-powered replication of Axelrod et al. (2015) finding that mind-wandering propensity can be increased by anodal tDCS. We used Bayesian statistics and a preregistered sequential-sampling design resulting in a total sample size of N = 192 participants collected across three different laboratories. Our findings show support against a stimulation effect on self-reported mind-wandering scores. The effect was small, in the opposite direction as predicted and not reliably different from zero. Using a Bayes Factor specifically designed to test for replication success, we found strong evidence against a successful replication of the original study. Finally, even when combining data from both the original and replication studies, we could not find evidence for an effect of anodal stimulation. Our results underline the importance of designing studies with sufficient power to detect evidence for or against behavioural effects of non-invasive brain stimulation techniques, preferentially using robust Bayesian statistics in preregistered reports.

Blinding is compromised for transcranial direct current stimulation at 1 mA for 20 min in young healthy adults.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that is frequently used to study cortical excitability changes and their impact on cognitive functions in humans. While most stimulators are capable of operating in double-blind mode, the amount of discomfort experienced during tDCS may break blinding. Therefore, specifically designed sham stimulation protocols are being used. The "fade-in, short-stimulation, fade-out" (FSF) protocol has been used in hundreds of studies and is commonly believed to be indistinguishable from real stimulation applied at 1 mA for 20 min. We analysed subjective reports of 192 volunteers, who either received real tDCS (n = 96) or FSF tDCS (n = 96). Participants reported more discomfort for real tDCS and correctly guessed the condition above chance-level. These findings indicate that FSF does not ensure complete blinding and that better active sham protocols are needed.

Modeling distracted performance.

The sustained attention to response task (SART) has been the primary method of studying the phenomenon of mind wandering. We develop and experimentally test the first integrated cognitive process model that quantitatively explains all stationary features of behavioral performance in the SART. The model assumes that performance is generated by a competitive race between a stimulus-related decision process and a stimulus-unrelated rhythmic response process. We propose that the stimulus-unrelated process entrains to timing regularities in the task environment, and is unconditionally triggered as a habit or 'insurance policy' to protect against the deleterious effects of mind wandering on ongoing task performance. For two SART experiments the model provided a quantitatively precise account of a range of previously reported trends in choice, response time and self-reported mind wandering data. It also accounted for three previously unidentified features of response time distributions that place critical constraints on cognitive models of performance in situations when people might engage in task-unrelated thoughts. Furthermore, the parameters of the rhythmic race model were meaningfully associated with participants' self-reported distraction, even though the model was never informed by these data. In a validation test, we disrupted the latent rhythmic component with a manipulation of inter-trial-interval variability, and showed that the architecture of the model provided insight into its counter-intuitive effect. We conclude that performance in the presence of mind wandering can be conceived as a competitive latent decision vs. rhythmic response process. We discuss how the rhythmic race model is not restricted to the study of distraction or mind wandering; it is applicable to any domain requiring repetitive responding where evidence accumulation is assumed to be an underlying principle of behavior.

When the brain takes a break: a model-based analysis of mind wandering.

Mind wandering is an ubiquitous phenomenon in everyday life. In the cognitive neurosciences, mind wandering has been associated with several distinct neural processes, most notably increased activity in the default mode network (DMN), suppressed activity within the anti-correlated (task-positive) network (ACN), and changes in neuromodulation. By using an integrative multimodal approach combining machine-learning techniques with modeling of latent cognitive processes, we show that mind wandering in humans is characterized by inefficiencies in executive control (task-monitoring) processes. This failure is predicted by a single-trial signature of (co)activations in the DMN, ACN, and neuromodulation, and accompanied by a decreased rate of evidence accumulation and response thresholds in the cognitive model.

Predictors of Response to Web-Based Cognitive Behavioral Therapy With High-Intensity Face-to-Face Therapist Guidance for Depression: A Bayesian Analysis.

BACKGROUND: Several studies have demonstrated the effect of guided Internet-based cognitive behavioral therapy (ICBT) for depression. However, ICBT is not suitable for all depressed patients and there is a considerable level of nonresponse. Research on predictors and moderators of outcome in ICBT is inconclusive. OBJECTIVE: This paper explored predictors of response to an intervention combining the Web-based program MoodGYM and face-to-face therapist guidance in a sample of primary care patients with mild to moderate depressive symptoms. METHODS: Participants (N=106) aged between 18 and 65 years were recruited from primary care and randomly allocated to a treatment condition or to a delayed treatment condition. The intervention included the Norwegian version of the MoodGYM program, face-to-face guidance from a psychologist, and reminder emails. In this paper, data from the treatment phase of the 2 groups was merged to increase the sample size (n=82). Outcome was improvement in depressive symptoms during treatment as assessed with the Beck Depression Inventory-II (BDI-II). Predictors included demographic variables, severity variables (eg, number of depressive episodes and pretreatment depression and anxiety severity), cognitive variables (eg, dysfunctional thinking), module completion, and treatment expectancy and motivation. Using Bayesian analysis, predictors of response were explored with a latent-class approach and by analyzing whether predictors affected the slope of response. RESULTS: A 2-class model distinguished well between responders (74%, 61/82) and nonresponders (26%, 21/82). Our results indicate that having had more depressive episodes, being married or cohabiting, and scoring higher on a measure of life satisfaction had high odds for positively affecting the probability of response. Higher levels of dysfunctional thinking had high odds for a negative effect on the probability of responding. Prediction of the slope of response yielded largely similar results. Bayes factors indicated substantial evidence that being married or cohabiting predicted a more positive treatment response. The effects of life satisfaction and number of depressive episodes were more uncertain. There was substantial evidence that several variables were unrelated to treatment response, including gender, age, and pretreatment symptoms of depression and anxiety. CONCLUSIONS: Treatment response to ICBT with face-to-face guidance may be comparable across varying levels of depressive severity and irrespective of the presence and severity of comorbid anxiety. Being married or cohabiting, reporting higher life satisfaction, and having had more depressive episodes may predict a more favorable response, whereas higher levels of dysfunctional thinking may be a predictor of poorer response. More studies exploring predictors and moderators of Internet-based treatments are needed to inform for whom this treatment is most effective. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry number: ACTRN12610000257066; https://www.anzctr.org.au/trial_view.aspx?id=335255 (Archived by WebCite at http://www.webcitation.org/6GR48iZH4).

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.

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.

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.

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.

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.