Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. METHODS: The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18-65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164). FINDINGS: Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; -8·2, SD 7·2) and the sham tDCS group (n=73; -8·0, 9·3; difference 0·3 [95% CI -2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028). INTERPRETATION: Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD. FUNDING: German Federal Ministry of Education and Research.

Insights into interoceptive and emotional processing: Lessons from studies on insular HD-tDCS.

Interoception, the processing of internal bodily signals, is proposed as the fundamental mechanism underlying emotional experiences. Interoceptive and emotional processing appear distorted in psychiatric disorders. However, our understanding of the neural structures involved in both processes remains limited. To explore the feasibility of enhancing interoception and emotion, we conducted two studies using high-definition transcranial direct current stimulation (HD-tDCS) applied to the right anterior insula. In study one, we compared the effects of anodal HD-tDCS and sham tDCS on interoceptive abilities (sensibility, confidence, accuracy, emotional evaluation) in 52 healthy subjects. Study two additionally included physical activation through ergometer cycling at the beginning of HD-tDCS and examined changes in interoceptive and emotional processing in 39 healthy adults. In both studies, HD-tDCS was applied in a single-blind cross-over online design with two separate sessions. Study one yielded no significant effects of HD-tDCS on interoceptive dimensions. In study two, significant improvements in interoceptive sensibility and confidence were observed over time with physical preactivation, while no differential effects were found between sham and insula stimulation. The expected enhancement of interoceptive and emotional processing following insula stimulation was not observed. We conclude that HD-tDCS targeting the insula does not consistently increase interoceptive or emotional variables. The observed increase in interoceptive sensibility may be attributed to the activation of the interoceptive network through physical activity or training effects. Future research on HD-tDCS involving interoceptive network structures could benefit from protocols targeting larger regions within the network, rather than focusing solely on insula stimulation.

Neurocognitive function as outcome and predictor for prefrontal transcranial direct current stimulation in major depressive disorder: an analysis from the DepressionDC trial.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex might beneficially influence neurocognitive dysfunctions associated with major depressive disorder (MDD). However, previous studies of neurocognitive effects of tDCS have been inconclusive. In the current study, we analyzed longitudinal, neurocognitive data from 101 participants of a randomized controlled multicenter trial (DepressionDC), investigating the efficacy of bifrontal tDCS (2 mA, 30 min/d, for 6 weeks) in patients with MDD and insufficient response to selective serotonin reuptake inhibitors (SSRI). We assessed whether active tDCS compared to sham tDCS elicited beneficial effects across the domains of memory span, working memory, selective attention, sustained attention, executive process, and processing speed, assessed with a validated, digital test battery. Additionally, we explored whether baseline cognitive performance, as a proxy of fronto-parietal-network functioning, predicts the antidepressant effects of active tDCS versus sham tDCS. We found no statistically significant group differences in the change of neurocognitive performance between active and sham tDCS. Furthermore, baseline cognitive performance did not predict the clinical response to tDCS. Our findings indicate no advantage in neurocognition due to active tDCS in MDD. Additional research is required to systematically investigate the effects of tDCS protocols on neurocognitive performance in patients with MDD.

Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D).

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) is currently evolving as an effective and safe therapeutic tool in the treatment of major depressive disorder (MDD). However, already established rTMS treatment paradigms are rather time-consuming. With theta burst stimulation (TBS), a patterned form of rTMS, treatment time can be substantially reduced. Pilot studies and a randomized controlled trial (RCT) demonstrate non-inferiority of TBS to 10 Hz rTMS and support a wider use in MDD. Still, data from placebo-controlled multicenter RCTs are lacking. In this placebo-controlled multicenter study, 236 patients with MDD will be randomized to either intermittent TBS (iTBS) to the left and continuous TBS (cTBS) to the right dlPFC or bilateral sham stimulation (1:1 ratio). The treatment will be performed with 80% resting motor threshold intensity over six consecutive weeks (30 sessions). The primary outcome is the treatment response rate (Montgomery-Asberg Depression Rating Scale reduction ≥ 50%). The aim of the study is to confirm the superiority of active bilateral TBS compared to placebo treatment. In two satellite studies, we intend to identify possible MRI-based and (epi-)genetic predictors of responsiveness to TBS therapy. Positive results will support the clinical use of bilateral TBS as an advantageous, efficient, and well-tolerated treatment and pave the way for further individualization of MDD therapy.Trial registration: ClinicalTrials.gov (NCT04392947).

Time Slices: What Is the Duration of a Percept?

We experience the world as a seamless stream of percepts. However, intriguing illusions and recent experiments suggest that the world is not continuously translated into conscious perception. Instead, perception seems to operate in a discrete manner, just like movies appear continuous although they consist of discrete images. To explain how the temporal resolution of human vision can be fast compared to sluggish conscious perception, we propose a novel conceptual framework in which features of objects, such as their color, are quasi-continuously and unconsciously analyzed with high temporal resolution. Like other features, temporal features, such as duration, are coded as quantitative labels. When unconscious processing is "completed," all features are simultaneously rendered conscious at discrete moments in time, sometimes even hundreds of milliseconds after stimuli were presented.

The neural correlates of flow experience explored with transcranial direct current stimulation.

The experience of flow ensues when humans engage in a demanding task while task demands are balanced with the individual's level of skill or ability. Here, we further tested the hypothesis that the medial prefrontal cortex (MPFC) plays a causal role in mediating flow experience using transcranial direct current stimulation (tDCS) to interfere with MPFC's deactivation evoked by a flow paradigm and measured by magnetic resonance (MR)-based perfusion imaging. In a balanced, within-subjects repeated measure design, three treatments of tDCS (sham, anodal, cathodal) were applied in a sample of 22 healthy male participants. tDCS-modulatory effects on flow-specific regional cerebral blood flow (rCBF) and subjective flow experience significantly depended on participants' baseline level of flow experience during sham tDCS. Those participants with lower-flow experience during sham tDCS (LF) benefitted from tDCS, particularly from the anodal polarity, whereas both active treatments did not substantially affect subjects with relatively higher baseline flow experience (HF). Functionally, in LF subjects, relative deactivation of the right amygdala got more pronounced under anodal and cathodal tDCS, and changed inconsistently in HF subjects. Inter-individual regression analyses of rCBF data suggested that involvement of the subgenual anterior cingulate cortex appears crucial for affecting the response pattern in the right amygdala and can be modulated by tDCS. Present data support the notion that valuable insights into the neural mechanism of flow can be obtained using tDCS. However, a clearer understanding of tDCS' baseline dependency in terms of individual variations in brain connectivity states appears a necessary prerequisite to exploit this technique further.

Theta-burst modulation of mid-ventrolateral prefrontal cortex affects salience coding in the human ventral tegmental area.

In the context of hedonic (over-)eating the ventral tegmental area (VTA) as a core part of the dopaminergic reward system plays a central role in coding incentive salience of high-caloric food. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate whether transcranial magnetic theta-burst stimulation (TBS) over the right mid-ventrolateral prefrontal cortex (mid-VLPFC) can induce modulation of calorie-sensitive brain activation in the VTA. The prefrontal location for TBS had been predetermined by seed-based resting-state fMRI with a functionally defined portion of the VTA serving as seed region obtained from an independent second fMRI experiment. In a sample of 15 healthy male participants, modulation of calorie-sensitive VTA activation did not significantly differ between the two TBS protocols. Comparisons with baseline revealed that both TBS protocols significantly affected calorie-sensitive neural processing of the mid-VLPFC in a rather similar way. In the VTA significant modulation of calorie-sensitive activation was observed after continuous TBS, whereas the modulatory effect of intermittent TBS was less reliable but also associated with a decrease of activation for high-caloric food images. Neurostimulation of right mid-VLPFC is suggestive as a main entry point of downstream signal changes for high- and low-caloric food cues that could enforce a shift in valuating stimuli of initially different incentive salience.

Development of rapid temporal processing and its impact on literacy skills in primary school children.

In a longitudinal study, auditory and visual temporal order thresholds (TOTs) were investigated in primary school children (N = 236; mean age at first data point = 6;7) at the beginning of Grade 1 and the end of Grade 2 to test whether rapid temporal processing abilities predict reading and spelling at the end of Grades 1 and 2. Auditory and visual TOTs differed but showed comparable developmental trajectories over 20 months. Visual TOTs were not predictive of literacy measures; auditory TOTs in Grade 1 were the best predictor. Interestingly, they were related to spelling in Grade 2 while auditory TOTs in Grade 2 were not, suggesting that rapid auditory processing abilities have a causal influence on literacy development.

Persistent predator-prey dynamics revealed by mass extinction.

Predator-prey interactions are thought by many researchers to define both modern ecosystems and past macroevolutionary events. In modern ecosystems, experimental removal or addition of taxa is often used to determine trophic relationships and predator identity. Both characteristics are notoriously difficult to infer in the fossil record, where evidence of predation is usually limited to damage from failed attacks, individual stomach contents, one-sided escalation, or modern analogs. As a result, the role of predation in macroevolution is often dismissed in favor of competition and abiotic factors. Here we show that the end-Devonian Hangenberg event (359 Mya) was a natural experiment in which vertebrate predators were both removed and added to an otherwise stable prey fauna, revealing specific and persistent trophic interactions. Despite apparently favorable environmental conditions, crinoids diversified only after removal of their vertebrate consumers, exhibiting predatory release on a geological time scale. In contrast, later Mississippian (359-318 Mya) camerate crinoids declined precipitously in the face of increasing predation pressure from new durophagous fishes. Camerate failure is linked to the retention of obsolete defenses or "legacy adaptations" that prevented coevolutionary escalation. Our results suggest that major crinoid evolutionary phenomena, including rapid diversification, faunal turnover, and species selection, might be linked to vertebrate predation. Thus, interactions observed in small ecosystems, such as Lotka-Volterra cycles and trophic cascades, could operate at geologic time scales and higher taxonomic ranks. Both trophic knock-on effects and retention of obsolete traits might be common in the aftermath of predator extinction.

Development, implementation, and evaluation of a movie-based curriculum to teach psychopathology.

BACKGROUND: Because medical students' attitudes toward psychiatry are often fostered by media, we provided an elective movie-based seminar to teach psychopathology. DESCRIPTION: We assessed attitudes toward psychiatry by using the Attitudes towards Psychiatry (ATP 35) scale in a pre-post design. Furthermore we evaluated the knowledge of diagnostic criteria in a pre-post design within one sample. EVALUATION: Of the 75 students who attended the seminar during 3 consecutive semesters, 54 (60.8% female) participated in the pre-post assessment. We observed a significant positive change in attitudes toward psychiatry and a significant gain of knowledge. CONCLUSIONS: Using movies is a feasible and effective method to teach psychiatry.

The Relation Between Subjective and Objective Measures of Visual Awareness: Current Evidence, Attempt of a Synthesis and Future Research Directions.

Within the realm of consciousness research, different methods of measuring the content of visual awareness are used: On the one hand, subjective measures require a report of sensory experiences related to a stimulus. On the other hand, objective measures rely on the observer's performance to accurately detect or discriminate the stimulus. The most appropriate measure of awareness is currently debated. To contribute to this debate, we review findings on the relation between subjective and objective measures of awareness. Although subjective measures sometimes lag behind objective measures, a substantial number of studies demonstrates a convergence of measures. Based on the reviewed studies, we identify five aspects relevant for achieving a convergence of measures. Future research could then identify and empirically test the boundary conditions, under which a convergence or divergence of subjective and measures of awareness is observed.

Cortical inhibition in attention deficit hyperactivity disorder: new insights from the electroencephalographic response to transcranial magnetic stimulation.

Attention deficit hyperactivity disorder is one of the most frequent neuropsychiatric disorders in childhood. Transcranial magnetic stimulation studies based on muscle responses (motor-evoked potentials) suggested that reduced motor inhibition contributes to hyperactivity, a core symptom of the disease. Here we employed the N100 component of the electroencephalographic response to transcranial magnetic stimulation as a novel marker for a direct assessment of cortical inhibitory processes, which has not been examined in attention deficit hyperactivity disorder so far. We further investigated to what extent affected children were able to regulate motor cortical inhibition, and whether effects of age on the electroencephalographic response to transcranial magnetic stimulation were compatible with either a delay in brain maturation or a qualitatively different development. N100 amplitude evoked by transcranial magnetic stimulation and its age-dependent development were assessed in 20 children with attention deficit hyperactivity disorder and 19 healthy control children (8-14 years) by 64-channel electroencephalography. Amplitude and latency of the N100 component were compared at rest, during response preparation in a forewarned motor reaction time task and during movement execution. The amplitude of the N100 component at rest was significantly lower and its latency tended to be shorter in children with attention deficit hyperactivity disorder. Only in controls, N100 amplitude to transcranial magnetic stimulation was reduced by response preparation. During movement execution, N100 amplitude decreased while motor evoked potential amplitudes showed facilitation, indicating that the electroencephalographic response to transcranial magnetic stimulation provides further information on cortical excitability independent of motor evoked potential amplitudes and spinal influences. Children with attention deficit hyperactivity disorder showed a smaller N100 amplitude reduction during movement execution compared with control children. The N100 amplitude evoked by transcranial magnetic stimulation decreased with increasing age in both groups. The N100 reduction in children with attention deficit hyperactivity disorder at all ages suggests a qualitative difference rather than delayed development of cortical inhibition in this disease. Findings further suggest that top-down control of motor cortical inhibition is reduced in children with attention deficit hyperactivity disorder. We conclude that evoked potentials in response to transcranial magnetic stimulation are a promising new marker of cortical inhibition in attention deficit hyperactivity disorder during childhood.

Subjective and objective measures of visual awareness converge.

Within consciousness research, the most appropriate assessment of visual awareness is matter of a controversial debate: Subjective measures rely on introspections of the observer related to perceptual experiences, whereas objective measures are based on performance of the observer to accurately detect or discriminate the stimulus in question across a series of trials. In the present study, we compared subjective and objective awareness measurements across different stimulus feature and contrast levels using a temporal two-alternative forced choice task. This task has the advantage to provide an objective psychophysical performance measurement, while minimizing biases from unconscious processing. Thresholds based on subjective ratings with the Perceptual Awareness Scale (PAS) and on performance accuracy were determined for detection (stimulus presence) and discrimination (letter case) tasks at high and low stimulus contrast. We found a comparable pattern of thresholds across tasks and contrasts for objective and subjective measurements of awareness. These findings suggest that objective performance measures based on accuracy and subjective ratings of the visual experience can provide similar information on the feature-content of a percept. The observed similarity of thresholds validates psychophysical and subjective approaches to awareness as providing converging and thus most likely veridical measures of awareness.

Exploring the after-effects of theta burst magnetic stimulation on the human motor cortex: a functional imaging study.

Theta burst stimulation (TBS) is a protocol of subthreshold repetitive transcranial magnetic stimulation (rTMS) inducing changes in cortical excitability. From functional imaging studies with conventional subthreshold rTMS protocols, it remains unclear what type of modulation occurs (direction and dependency to neural activity) and whether putative effects are bound to unspecific changes in cerebral perfusion or require a functional challenge. In a within-subjects (n = 17) repeated measurement design including real TBS and a control session without stimulation, we examined neural activation in a choice-reaction task after application of intermittent TBS, a protocol, which enhances cortical excitability over the left motor cortex (M1). Brain activity was monitored by blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging interleaved with measuring regional cerebral blood flow (rCBF) at rest using MR-based perfusion imaging. On a separate day, TMS-induced compound muscle action potentials (cMAPs) amplitude of the right hand was measured after excitatory TBS. Compared to control, a significant decrease in BOLD signal due to right hand motor activity during the choice-reaction task was observed mainly in the stimulated M1 and motor-related remote areas after stimulation. This decrease might represent a facilitating effect, because cMAPs amplitude increased upon TBS compared to control. No changes in rCBF at rest were observed. The data demonstrate that subthreshold intermittent TBS targets both the stimulated cortical area as well as remote areas. The facilitation changing the efficacy of neural signal transmission seems to be reflected by a BOLD signal decrease, whereas the network at rest does not appear to be affected.

Exploring the affective component of pain perception during aversive stimulation in borderline personality disorder.

In a pilot study, affective components of pain were assessed using repetitive peripheral magnetic stimulation (rPMS) in patients with borderline personality disorder and healthy controls. Significant differences in pain thresholds and in affective components of pain between both groups were found. rPMS was well tolerated and suitable for assessing pain.

Effect of TMS on oculomotor behavior but not perceptual stability during smooth pursuit eye movements.

During smooth pursuit eye movements, we do not mistake the shift of the retinal image induced by the visual background for motion of the world around us but instead perceive a stable world. The goal of this study was to search for the neuronal substrates providing perceptual stability. To this end, pursuit eye movements across a background stimulus and perceptual stability were measured in the absence and presence, respectively, of transcranial magnetic stimulation (TMS) applied to 6 different brain regions, that is, primary visual cortex (V1), area MT+/V5, left and right temporoparietal junctions (TPJs), medial parieto-occipital cortex (POC), and the lateral cerebellum (LC). Stimulation of MT+/V5 and the cerebellum induced significant decreases in pursuit gain independent of background presentation, whereas stimulation of TPJ impaired the suppression of the optokinetic reflex induced by background stimulation. In contrast to changes in pursuit, only nonsignificant modifications in perceptual stability were observed. We conclude that MT+/V5, TPJ, and the LC contribute to pursuit eye movements and that TPJ supports the suppression of optokinesis. The lack of significant influences of TMS on perception suggests that motion perception invariance is not based on a localized but rather a highly distributed network featuring parallel processing.

The relationship between cholinergic system brain structure and function in healthy adults and patients with mild cognitive impairment.

We assessed the structure-function relationship of the human cholinergic system and hypothesized that structural measures are associated with short-latency sensory afferent inhibition (SAI), an electrophysiological measure of central cholinergic signal transmission. Healthy volunteers (n = 36) and patients with mild cognitive impairment (MCI, n = 20) underwent median nerve SAI and 3T structural MRI to determine the volume of the basal forebrain and the thalamus. Patients with MCI had smaller basal forebrain (p < 0.001) or thalamus volumes (p < 0.001) than healthy volunteers. Healthy SAI responders (> 10% SAI) had more basal forebrain volume than non-responders (p = 0.004) or patients with MCI (p < 0.001). More basal forebrain volume was associated with stronger SAI in healthy volunteers (r = 0.33, p < 0.05) but not patients with MCI. There was no significant relationship between thalamus volumes and SAI. Basal forebrain volume is associated with cholinergic function (SAI) in healthy volunteers but not in MCI patients. The in-vivo investigation of the structure-function relationship could further our understanding of the human cholinergic system in patients with suspected or known cholinergic system degeneration.

Functional and structural impairment of transcallosal motor fibres in ALS: a study using transcranial magnetic stimulation, diffusion tensor imaging, and diffusion weighted spectroscopy.

Imaging studies showed that the structure of the corpus callosum (CC) is affected in amyotrophic lateral sclerosis (ALS). Some clinical studies also suggest that interhemispheric connectivity is altered, since mirror movements seem to occur in ALS. Finally, reduced interhemispheric inhibition (IHI), studied by transcranial magnetic stimulation (TMS), has been reported. It is not known whether there is any association between these findings. Here, we studied the integrity of the CC in ALS on the morphological, the functional, the electrophysiological, and the clinical level. Twenty-seven right-handed ALS patients and 21 healthy right-handed controls were included. Mirror activity (MA) was quantified using surface EMG. Diffusion tensor imaging tractography was used to segment the CC and quantify fractional anisotropy (FA). We studied the diffusivity of the intra-axonal markers N-acetylaspartate+N-acetyl aspartyl glutamate D(tNAA) within the CC. IHI was studied as a marker of CC function using a double-pulse TMS protocol. ALS patients showed significantly decreased FA in the motor segment of the CC (p < 0.01), and IHI was significantly reduced compared to controls (p = 0.01). However, no differences were observed regarding D(tNAA) and MA. The morphological as well as the functional integrity of the CC are altered in ALS. IHI was reduced in ALS, associated with decreased FA in the motor CC. Patients did not exhibit increased MA. Also, no differences within the CC were observed using diffusion-weighted spectroscopy. IHI might serve as a marker of transcallosal pathway disruption in ALS, even before clinical deficits become apparent.

Xenon-induced changes in CNS sensitization to pain.

Electrophysiological investigations of the spinal cord in animals have shown that pain sensitizes the central nervous system via glutamate receptor dependent long-term potentiation (LTP) related to an enhancement of pain perception. To expand these findings, we used functional magnetic resonance (fMRI), blood oxygen level dependent (BOLD) and perfusion imaging in combination with repeated electrical stimulation in humans. Specifically we monitored modulation of somatosensory processing during inhibition of excitatory transmission by ocular application of the glutamate receptor antagonist xenon. BOLD responses upon secondary stimulation increased in mid insular and in primary/secondary sensory cortices under placebo and decreased under xenon treatments. Xenon-induced decreases in regional perfusion were confined to stimulation responsive brain regions and correlated with time courses of xenon concentrations in the cranial blood. Moreover, effects of xenon on behavioral, fMRI and perfusion data scaled with stimulus intensity. The dependence of pain sensitization on sufficient pre-activation reflects a multistage process which is characteristic for glutamate receptor related processes of LTP. This study demonstrates how LTP related processes known from the cellular level can be investigated at the brain systems level.

When transcranial magnetic stimulation (TMS) modulates feature integration.

How the brain integrates visual information across time into coherent percepts is an open question. Here, we presented two verniers with opposite offset directions one after the other. A vernier consists of two vertical bars that are horizontally offset. When the two verniers are separated by a blank screen (interstimulus interval, ISI), the two verniers are perceived either as two separate entities or as one vernier with the offset moving from one side to the other depending on the ISI. In both cases, their offsets can be reported independently. Transcranial magnet stimulation (TMS) over the occipital cortex does not interfere with the offset discrimination of either vernier. When a grating, instead of the ISI, is presented, the two verniers are not perceived separately anymore, but as 'one' vernier with 'one' fused vernier offset. TMS strongly modulates the percept of the fused vernier offset even though the spatio-temporal position of the verniers is identical in the ISI and grating conditions. We suggest that the grating suppresses the termination signal of the first vernier and the onset signal of the second vernier. As a consequence, perception of the individual verniers is suppressed. Neural representations of the vernier and second vernier inhibit each other, which renders them vulnerable to TMS for at least 300 ms, even though stimulus presentation was only 100 ms. Our data suggest that stimulus features can be flexibly integrated in the occipital cortex, mediated by neural interactions with outlast stimulus presentations by far.