Reduced past-oriented mind wandering in left compared to right medial temporal lobe epilepsy.

Mind wandering refers to a shift of attention away from a task at hand to task-unrelated thoughts. Several groups have shown increased activation of the left medial temporal lobe (MTL) before and during spontaneous thoughts suggesting that the left MTL may play a crucial role in mind wandering. Due to its relevance for long-term memory, we further hypothesized that the left MTL is particularly involved in mind wandering towards the past. Accordingly, we predicted a reduced propensity to mind wander and less past-oriented mind wandering in patients with left MTL epilepsies. To this end, we experimentally investigated mind wandering in 89 in-patients undergoing diagnostic evaluation of their putative epileptic disorder. Patients performed a sustained attention to response task with embedded experience sampling probes aiming to assess occurrence, meta-awareness and temporal orientation (past/present/future) of mind-wandering episodes. We did not find significant differences in the propensity to mind wander between patient subgroups. However, the left MTL epilepsy subgroup showed significantly reduced past-oriented mind wandering compared to right MTL epilepsies, as well as a trend towards diminished past-oriented mind wandering compared to idiopathic epilepsies. Possibly due to compensatory mechanisms, the right MTL epilepsy subgroup showed significantly increased past-oriented mind wandering compared to extratemporal epilepsies and patients with syncopes. These behavioural findings point to a rejection of the hypothesis that the amount of time engaged in mind wandering crucially depends on the left MTL. However, our data do support the idea that the left MTL is particularly involved in mind wandering towards the past.

Memory encoding-related anterior hippocampal potentials are modulated by deep brain stimulation of the entorhinal area.

BACKGROUND: Deep brain stimulation (DBS) of the human entorhinal area using 50 Hz pulses has revealed conflicting results regarding memory performance. Moreover, its impact on memory-related hippocampal potentials has not yet been investigated. METHODS: We recorded data from seven epilepsy patients implanted with depth electrodes in the entorhinal cortex, hippocampus, amygdala, and parahippocampal cortex. Entorhinal DBS (bipolar, biphasic 50 Hz pulses, on- and off-cycles of 15 s) was applied with low amplitude (0.1 mA) to resemble physiologic conditions. During DBS on- and off-periods, patients learned noun-color associations that were later tested. RESULTS: During entorhinal DBS we observed more positive deflections of event-related potentials (ranging from 700 to 950 ms) in the anterior hippocampus for the on- vs. off-condition. We detected no effects in the amygdala, mid hippocampus and parahippocampal cortex. On the behavioral level, no differences in memory performance (item and source memory) were apparent in the on- vs. off-condition, neither across all trials nor across patients. DISCUSSION: Our findings indicate that entorhinal DBS with low amplitude has an impact on memory encoding-related potentials within the anterior hippocampus, but not on memory performance per se.

The POU factor ventral veins lacking/Drifter directs the timing of metamorphosis through ecdysteroid and juvenile hormone signaling.

Although endocrine changes are known to modulate the timing of major developmental transitions, the genetic mechanisms underlying these changes remain poorly understood. In insects, two developmental hormones, juvenile hormone (JH) and ecdysteroids, are coordinated with each other to induce developmental changes associated with metamorphosis. However, the regulation underlying the coordination of JH and ecdysteroid synthesis remains elusive. Here, we examined the function of a homolog of the vertebrate POU domain protein, Ventral veins lacking (Vvl)/Drifter, in regulating both of these hormonal pathways in the red flour beetle, Tribolium castaneum (Tenebrionidae). RNA interference-mediated silencing of vvl expression led to both precocious metamorphosis and inhibition of molting in the larva. Ectopic application of a JH analog on vvl knockdown larvae delayed the onset of metamorphosis and led to a prolonged larval stage, indicating that Vvl acts upstream of JH signaling. Accordingly, vvl knockdown also reduced the expression of a JH biosynthesis gene, JH acid methyltransferase 3 (jhamt3). In addition, ecdysone titer and the expression of the ecdysone response gene, hormone receptor 3 (HR3), were reduced in vvl knockdown larvae. The expression of the ecdysone biosynthesis gene phantom (phm) and spook (spo) were reduced in vvl knockdown larvae in the anterior and posterior halves, respectively, indicating that Vvl might influence ecdysone biosynthesis in both the prothoracic gland and additional endocrine sources. Injection of 20-hydroxyecdysone (20E) into vvl knockdown larvae could restore the expression of HR3 although molting was never restored. These findings suggest that Vvl coordinates both JH and ecdysteroid biosynthesis as well as molting behavior to influence molting and the timing of metamorphosis. Thus, in both vertebrates and insects, POU factors modulate the production of major neuroendocrine regulators during sexual maturation.

Intracranial electroencephalography power and phase synchronization changes during monaural and binaural beat stimulation.

Auditory stimulation with monaural or binaural auditory beats (i.e. sine waves with nearby frequencies presented either to both ears or to each ear separately) represents a non-invasive approach to influence electrical brain activity. It is still unclear exactly which brain sites are affected by beat stimulation. In particular, an impact of beat stimulation on mediotemporal brain areas could possibly provide new options for memory enhancement or seizure control. Therefore, we examined how electroencephalography (EEG) power and phase synchronization are modulated by auditory stimulation with beat frequencies corresponding to dominant EEG rhythms based on intracranial recordings in presurgical epilepsy patients. Monaural and binaural beat stimuli with beat frequencies of 5, 10, 40 and 80 Hz and non-superposed control signals were administered with low amplitudes (60 dB SPL) and for short durations (5 s). EEG power was intracranially recorded from mediotemporal, temporo-basal and temporo-lateral and surface sites. Evoked and total EEG power and phase synchronization during beat vs. control stimulation were compared by the use of Bonferroni-corrected non-parametric label-permutation tests. We found that power and phase synchronization were significantly modulated by beat stimulation not only at temporo-basal, temporo-lateral and surface sites, but also at mediotemporal sites. Generally, more significant decreases than increases were observed. The most prominent power increases were seen after stimulation with monaural 40-Hz beats. The most pronounced power and synchronization decreases resulted from stimulation with monaural 5-Hz and binaural 80-Hz beats. Our results suggest that beat stimulation offers a non-invasive approach for the modulation of intracranial EEG characteristics.

Transcranial electrical stimulation modifies the neuronal response to psychosocial stress exposure.

Stress is a constant characteristic of everyday life in our society, playing a role in triggering several chronic disorders. Therefore, there is an ongoing need to develop new methods in order to manage stress reactions. The regulatory function of right medial-prefrontal cortex (mPFC) is frequently reported by imaging studies during psychosocial stress situations. Here, we examined the effects of inhibitory and excitatory preconditioning stimulation via cathodal and anodal transcranial direct current stimulation (tDCS) on psychosocial stress related behavioral indicators and physiological factors, including the cortisol level in the saliva and changes in brain perfusion. Twenty minutes real or sham tDCS was applied over the right mPFC of healthy subjects before the performance of the Trier Social Stress Test (TSST). Regional cerebral blood flow (rCBF) was measured during stimulation and after TSST, using pseudo-continuous arterial spin labeling (pCASL). Comparing the effect of the different stimulation conditions, during anodal stimulation we found higher rCBF in the right mPFC, compared to the sham and in the right amygdala, superior PFC compared to the cathodal condition. Salivary cortisol levels showed a decrease in the anodal and increase in cathodal groups after completion of the TSST. The behavioral stress indicators indicated the increase of stress level, however, did not show any significant differences among groups. In this study we provide the first insights into the neuronal mechanisms mediating psychosocial stress responses by prefrontal tDCS.

Insights into the time course of mind wandering during task execution.

Our minds tend to wander, sometimes with little control. Despite this phenomenon, that can affect our ability to perform everyday tasks gaining much interest, relatively little is understood about the actual time course of MW across an experimental task. With this in mind, we collated data from two previously reported studies investigating the effect of auditory beat stimulation on MW. Taking experience sampling probes intermittently dispersed throughout a sustained-attention-to-response task (SART), we re-evaluated responses to theta monaural beat stimulation, as well as to two control conditions (silence (headphones only) and a sine wave control tone). The experience sampling probes were binned into shorter intervals of approximately five minutes duration, chronologically as they appeared within the paradigm. Experience sampling probes assayed whether MW had occurred, with or without meta-awareness, and lastly in which temporal orientation (past/present/future). By applying this somewhat temporally better resolved approach, we were able to examine the time course of attentional fluctuations related to MW during the execution of the SART, as well as interactions arising from the auditory beat stimulation. As anticipated, MW increased during task execution, most prominently at the beginning of the experiment. We also observed that levels of meta-awareness declined over time. Moreover, the temporal evolution of meta-awareness and past-orientation appeared to depend on the stimulation condition. These data demonstrate that time-on-task is a crucial factor in measuring MW, during the performance of an attentional task.

Side effects of monaural beat stimulation during sustained mental work on mind wandering and performance measures.

Excessive mind wandering (MW) contributes to the development and maintenance of psychiatric disorders. Previous studies have suggested that auditory beat stimulation may represent a method enabling a reduction of MW. However, little is known about how different auditory stimulation conditions are subjectively perceived and whether this perception is in turn related to changes in subjective states, behavioral measures of attention and MW. In the present study, we therefore investigated MW under auditory beat stimulation and control conditions using experience sampling during a sustained attention to response task (SART). The subjective perception of the stimulation conditions, as well as changes in anxiety, stress and negative mood after versus before stimulation were assessed via visual-analog scales. Results showed that any auditory stimulation applied during the SART was perceived as more distracting, disturbing, uncomfortable and tiring than silence and was related to more pronounced increases of stress and negative mood. Importantly, the perception of the auditory conditions as disturbing was directly correlated with MW propensity. Additionally, distracting, disturbing and uncomfortable perceptions predicted negative mood. In turn, negative mood was inversely correlated with response accuracy for target stimuli, a behavioral indicator of MW. In summary, our data show that MW and attentional performance are affected by the adverse perception of auditory stimulation, and that this influence may be mediated by changes in mood.

Mind wandering in anxiety disorders: A status report.

Many investigations have targeted the subject of worry in anxiety disorders. Worry can be regarded as a subtype of mind wandering (MW), which is undeliberate, perseverative, negatively-valenced, and mainly future-oriented. Nevertheless, until now only a few studies have explored the role of overall MW in the origin and course of anxiety disorders. To foster progress in this field, we briefly describe and discuss relevant studies addressing MW in subjects with anxiety disorders or symptoms or disorders associated with anxiety symptoms. Provisional synthesis suggests that: a) the overall amount of MW is positively correlated with anxiety symptoms; b) MW characteristics reflecting worry and rumination appear to be relevant in anxiety; c) comorbid depressive and ADHD symptoms may contribute to excessive MW in anxiety; d) MW-related therapeutic interventions may be useful as complementary treatments in anxiety disorders. However, more studies related to MW in anxiety disorders or symptoms are necessary to corroborate and extend these initial findings. Such investigations should ideally combine experience sampling with self-rating assessments of both MW and worry/rumination.

Mind wandering and depression: A status report.

While many clinical studies and overviews on the contribution of rumination to depression exist, relatively little information regarding the role of mind wandering (MW) in general is available. Therefore, it remains an open question whether patterns of MW are altered in depression and, if so, how these alterations are related to rumination. Here, we review and discuss studies investigating MW in cohorts, showing either a clinically significant depression or with clinically significant disorders accompanied by depressive symptoms. These studies yield first tentative insights into major issues. However, further investigations are required, specifically studies which: i) compare patients with a primary diagnosis of major depression with healthy and appropriately matched controls, ii) implement measures of both MW and rumination, iii) are based on experience sampling (in combination with other key approaches), iv) compare experience sampling during daily life, resting state and attentional tasks, v) explore possible biases in the assessment of MW, vi) acquire data not only related to the propensity and contents of MW, but also regarding meta-awareness and intentionality.

Modulation of Mind Wandering Using Monaural Beat Stimulation in Subjects With High Trait-Level Mind Wandering.

Mind wandering (MW) refers to a state when attention shifts from the task at hand or current situation toward thoughts, feelings, and imaginations. This state is often accompanied by a decline in mood, and patients suffering from major depression exhibit more perseverative MW. Hence, although the directionality of the relationship between mood and MW is still under investigation, it may be useful to explore possible avenues to reduce MW. In an earlier pilot study, we investigated MW during auditory beat stimulation in healthy subjects using thought-probes during a sustained attention to response task (SART). We found evidence for reduced MW during monaural 5 Hz beats compared to silence, sine tones, and binaural 5 Hz beats. Moreover, the data tentatively suggested that this reduction was particularly pronounced in subjects with high levels of MW during silence. In the current study, we therefore asked whether MW can be reduced by monaural theta beats in subjects with high trait-levels of MW, as indicated by an online MW questionnaire. Preselected subjects performed a SART task with thought-probes assessing the propensity to mind wander, meta-awareness, and the temporal orientation of MW. Stimulation conditions comprised monaural theta beats, as well as silence (headphones on), and sine tones as control conditions. Our main hypothesis stating that the propensity to mind wander during monaural theta beats is reduced compared to both control conditions was only partly confirmed. Indeed, MW was significantly diminished during exposure to the theta beats compared to sine tones. However, reduced MW during theta beats versus silence was only observed in a subgroup using stricter inclusion criteria. Considering possible reasons for this outcome, our data suggest that the preselection procedure was suboptimal and that beat effects are modulated by the individual responses to auditory stimulation in general.

Neuropsychological features of mind wandering in left-, right- and extra temporal lobe epilepsy.

PURPOSE: Mind wandering, i.e. mental time-travelling and imagery unrelated to the current situation has recently been related to mesial temporal lobe (memory) function. In this regard we evaluated as to whether parameters of mind wandering are related to material specific memory in patients with a left-, right-, or extra- temporal lobe epilepsy. METHODS: In this prospective controlled study we analyzed mind wandering, material specific memory, and executive functions in 29 right-handed patients with right-, left-, or extra-temporal lobe epilepsies. Mind wandering was assessed with a sustained attention to response task containing embedded inquiries on mind wandering. In addition, verbal list learning and memory (VLMT), design list learning (DCS-R), and executive function (EpiTrack) were assessed. RESULTS: In patients with right temporal lobe epilepsy, the propensity to mind wander was positively related to verbal memory performance, while in left temporal lobe epilepsy, the propensity and future related mind wandering were positively correlated to the performance in visual/figural memory. Generally, the propensity of MW was related to executive function as well. CONCLUSION: The results suggest that mind wandering in lateralized temporal lobe epilepsy appears to be non-specifically driven by executive function and specifically by the mode and functionality of the memory system of the non-epileptic hemisphere. Repeated assessments would be required to discern as to how much such patterns depend on lesions versus epileptic dysfunction and whether they change with successful medical or surgical treatment.

On the relationship between mind wandering and mindfulness.

Mind wandering (MW) and mindfulness have both been reported to be vital moderators of psychological wellbeing. Here, we aim to examine how closely associated these phenomena are and evaluate the psychometrics of measures often used to quantify them. We investigated two samples, one consisting of German-speaking unpaid participants (GUP, n [Formula: see text] 313) and one of English-speaking paid participants (EPP, n [Formula: see text] 228) recruited through MTurk.com. In an online experiment, we collected data using the Mindful Attention Awareness Scale (MAAS) and the sustained attention to response task (SART) during which self-reports of MW and meta-awareness of MW were recorded using experience sampling (ES) probes. Internal consistency of the MAAS was high (Cronbachs [Formula: see text] of 0.96 in EPP and 0.88 in GUP). Split-half reliability for SART measures and self-reported MW was overall good with the exception of SART measures focusing on Nogo trials, and those restricted to SART trials preceding ES in a 10 s time window. We found a moderate negative association between trait mindfulness and MW as measured with ES probes in GUP, but not in EPP. Our results suggest that MW and mindfulness are on opposite sides of a spectrum of how attention is focused on the present moment and the task at hand.

UCHL5 controls ß-catenin destruction complex function through Axin1 regulation.

Wnt/ß-catenin signaling is crucially involved in many biological processes, from embryogenesis to cancer development. Hence, the complete understanding of its molecular mechanism has been the biggest challenge in the Wnt research field. Here, we identified ubiquitin C-terminal hydrolase like 5 (UCHL5), a deubiquitinating enzyme, as a novel negative regulator of Wnt signaling, upstream of ß-catenin. The study further revealed that UCHL5 plays an important role in the ß-catenin destruction complex, as it physically interacts with multiple domains of Axin1 protein. Our functional analyses also elucidated that UCHL5 is required for both the stabilization and the polymerization of Axin1 proteins. Interestingly, although these events are governed by deubiquitination in the DIX domain of Axin1 protein, they do not require the deubiquitinating activity of UCHL5. The study proposes a novel molecular mechanism of UCHL5 potentiating the functional activity of Axin1, a scaffolder of the ß-catenin destruction complex.

Evaluating aftereffects of short-duration transcranial random noise stimulation on cortical excitability.

A 10-minute application of highfrequency (100-640 Hz) transcranial random noise stimulation (tRNS) over the primary motor cortex (M1) increases baseline levels of cortical excitability, lasting around 1 hr poststimulation Terney et al. (2008). We have extended previous work demonstrating this effect by decreasing the stimulation duration to 4, 5, and 6 minutes to assess whether a shorter duration of tRNS can also induce a change in cortical excitability. Single-pulse monophasic transcranial magnetic stimulation (TMS) was used to measure baseline levels of cortical excitability before and after tRNS. A 5- and 6-minute tRNS application induced a significant facilitation. 4-minute tRNS produced no significant aftereffects on corticospinal excitability. Plastic after effects after tRNS on corticospinal excitability require a minimal stimulation duration of 5 minutes. However, the duration of the aftereffect of 5-min tRNS is very short compared to previous studies using tRNS. Developing different transcranial stimulation techniques may be fundamental in understanding how excitatory and inhibitory networks in the human brain can be modulated and how each technique can be optimised for a controlled and effective application.

Neural activity in the human anterior thalamus during natural vision.

In natural vision humans and other primates explore environment by active sensing, using saccadic eye movements to relocate the fovea and sample different bits of information multiple times per second. Saccades induce a phase reset of ongoing neuronal oscillations in primary and higher-order visual cortices and in the medial temporal lobe. As a result, neuron ensembles are shifted to a common state at the time visual input propagates through the system (i.e., just after fixation). The extent of the brain's circuitry that is modulated by saccades is not yet known. Here, we evaluate the possibility that saccadic phase reset impacts the anterior nuclei of the thalamus (ANT). Using recordings in the human thalamus of three surgical patients during natural vision, we found that saccades and visual stimulus onset both modulate neural activity, but with distinct field potential morphologies. Specifically, we found that fixation-locked field potentials had a component that preceded saccade onset. It was followed by an early negativity around 50 ms after fixation onset which is significantly faster than any response to visual stimulus presentation. The timing of these events suggests that the ANT is predictively modulated before the saccadic eye movement. We also found oscillatory phase concentration, peaking at 3-4 Hz, coincident with suppression of Broadband High-frequency Activity (BHA; 80-180 Hz), both locked to fixation onset supporting the idea that neural oscillations in these nuclei are reorganized to a low excitability state right after fixation onset. These findings show that during real-world natural visual exploration neural dynamics in the human ANT is influenced by visual and oculomotor events, which supports the idea that ANT, apart from their contribution to episodic memory, also play a role in natural vision.

Auditory Beat Stimulation Modulates Memory-Related Single-Neuron Activity in the Human Medial Temporal Lobe.

Auditory beats are amplitude-modulated signals (monaural beats) or signals that subjectively cause the perception of an amplitude modulation (binaural beats). We investigated the effects of monaural and binaural 5 Hz beat stimulation on neural activity and memory performance in neurosurgical patients performing an associative recognition task. Previously, we had reported that these beat stimulation conditions modulated memory performance in opposite directions. Here, we analyzed data from a patient subgroup, in which microwires were implanted in the amygdala, hippocampus, entorhinal cortex and parahippocampal cortex. We identified neurons responding with firing rate changes to binaural versus monaural 5 Hz beat stimulation. In these neurons, we correlated the differences in firing rates for binaural versus monaural beats to the memory-related differences for remembered versus forgotten items and associations. In the left hemisphere, we detected statistically significant negative correlations between firing rate differences for binaural versus monaural beats and remembered versus forgotten items/associations. Importantly, such negative correlations were also observed between beat stimulation-related firing rate differences in the pre-stimulus window and memory-related firing rate differences in the post-stimulus windows. In line with concepts of homeostatic plasticity, our findings suggest that beat stimulation is linked to memory performance via shifting baseline firing levels.

Low Intensity, Transcranial, Alternating Current Stimulation Reduces Migraine Attack Burden in a Home Application Set-Up: A Double-Blinded, Randomized Feasibility Study.

Background: Low intensity, high-frequency transcranial alternating current stimulation (tACS) applied over the motor cortex decreases the amplitude of motor evoked potentials. This double-blind, placebo-controlled parallel group study aimed to test the efficacy of this method for acute management of migraines. Methods: The patients received either active (0.4 mA, 140 Hz) or sham stimulation for 15 min over the visual cortex with the number of terminated attacks two hours post-stimulation as the primary endpoint, as a home therapy option. They were advised to treat a maximum of five migraine attacks over the course of six weeks. Results: From forty patients, twenty-five completed the study, sixteen in the active and nine in the sham group with a total of 102 treated migraine attacks. The percentage of terminated migraine attacks not requiring acute rescue medication was significantly higher in the active (21.5%) than in the sham group (0%), and the perceived pain after active stimulation was significantly less for 2-4 h post-stimulation than after sham stimulation. Conclusion: tACS over the visual cortex has the potential to terminate migraine attacks. Nevertheless, the high drop-out rate due to compliance problems suggests that this method is impeded by its complexity and time-consuming setup.

Increasing human brain excitability by transcranial high-frequency random noise stimulation.

For >20 years, noninvasive transcranial stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS) have been used to induce neuroplastic-like effects in the human cortex, leading to the activity-dependent modification of synaptic transmission. Here, we introduce a novel method of electrical stimulation: transcranial random noise stimulation (tRNS), whereby a random electrical oscillation spectrum is applied over the motor cortex. tRNS induces consistent excitability increases lasting 60 min after stimulation. These effects have been observed in 80 subjects through both physiological measures and behavioral tasks. Higher frequencies (100-640 Hz) appear to be responsible for generating this excitability increase, an effect that may be attributed to the repeated opening of Na(+) channels. In terms of efficacy tRNS appears to possess at least the same therapeutic potential as rTMS/tDCS in diseases such as depression, while furthermore avoiding the constraint of current flow direction sensitivity characteristic of tDCS.

Short-duration transcranial random noise stimulation induces blood oxygenation level dependent response attenuation in the human motor cortex.

Manipulation of cortical excitability can be experimentally achieved by the application of transcranial random noise stimulation (tRNS). TRNS is a novel method of non-invasive electrical brain stimulation whereby a random electrical oscillation spectrum is applied over the cortex. A previous study recently reported that application of weak 10-min tRNS over primary motor cortex (M1) enhances corticospinal excitability both during and after stimulation in the healthy human brain. Here, blood oxygenation level dependent (BOLD) MRI was used to monitor modulations in human sensorimotor activity after the application of 4-min tRNS. Activation maps for a right hand index-thumb finger opposition task were obtained for nine subjects after sham and 1-mA tRNS in separate sessions. TRNS of the left-hemispheric sensorimotor cortex resulted in a decrease in the mean number of activated pixels by 17%, in the hand area. Our results indicate that tRNS applied with different durations and/or in combination with a task might result in different outcomes. Application of tRNS to the human cortex allows an unnoticeable and thus painless, selective, non-invasive and reversible activity change within the cortex, its main advantage being the direction insensitivity of the stimulation. TRNS also provides a qualitatively new way of producing and interfering with brain plasticity, although, further research is required to optimise stimulation parameters and efficacy.

New perspectives for the modulation of mind-wandering using transcranial electric brain stimulation.

When our attention is decoupled from an ongoing task and becomes coupled to thoughts and feelings not being subject to task engagement, we are mind-wandering. This transient and pervasive mental process can occupy a considerable amount of our waking hours. Mind-wandering is understood to exert both positive and negative effects on well-being, and has been shown to play a role in mood disorders and depression. Here we summarize recent research aiming to investigate whether states of mind-wandering can be modulated using transcranial direct current stimulation (tDCS), a non-invasive, reversible means of altering neuronal excitability and in turn, cortical activity. We examine and compare the methodologies underlying the existing studies on this topic, and evaluate the commonalities and contrasts of their outcomes. So far, existing studies tentatively suggest an influence of tDCS on the contents and propensity to mind-wander. However, these studies exhibit considerable methodological differences and changes in the propensity to mind-wander are inconsistent with task performance. Moreover, replication of the results of two studies from the same group by another group has recently failed. We discuss the implications of these findings, in particular, regarding therapeutic targets in mood disorders, and propose perspectives for future investigations. For instance, tDCS effects on deliberate versus undeliberate mind-wandering should be disentangled. The hippocampus as an important hub for mind-wandering-related processes may be targeted. Most importantly, research efforts related to mind-wandering and rumination should be integrated.