From epidemic to pandemic: Effects of the COVID-19 outbreak on high school program choices in Sweden.

We study whether the onset of the COVID-19 crisis affected the program choices of high school applicants in Sweden. Our analysis exploits the fact that the admission process consists of two stages: a preliminary round in which applicants initially rank programs in order of preference and a final round in which they can alter their preliminary rankings. In 2020, the timing of the two rounds happened to provide a unique pre- and post-crisis snapshot of applicants' field-of-study choices. Using school-level data on applicants' top-ranked programs for all admission rounds between 2016 and 2020, we implement a difference-in-differences method to identify the immediate effect of the crisis on demand for programs. We find no change in demand for academic programs, but a decline in top-ranked applications to some of the vocational programs. The declines are most pronounced and robust for programs related to the Accommodation and Food Services sector, which was the most adversely affected industry during the crisis. This finding suggests that labor market considerations influence the study choices made by relatively young students.

Satellite-derived multivariate world-wide lake physical variable timeseries for climate studies.

A consistent dataset of lake surface water temperature, ice cover, water-leaving reflectance, water level and extent is presented. The collection constitutes the Lakes Essential Climate Variable (ECV) for inland waters. The data span combined satellite observations from 1992 to 2020 inclusive and quantifies over 2000 relatively large lakes, which represent a small fraction of the number of lakes worldwide but a significant fraction of global freshwater surface. Visible and near-infrared optical imagery, thermal imagery and microwave radar data from satellites have been exploited. All observations are provided in a common grid at 1/120° latitude-longitude resolution, jointly in daily files. The data/algorithms have been validated against in situ measurements where possible. Consistency analysis between the variables has guided the development of the joint dataset. It is the most complete collection of consistent satellite observations of the Lakes ECV currently available. Lakes are of significant interest to scientific disciplines such as hydrology, limnology, climatology, biogeochemistry and geodesy. They are a vital resource for freshwater supply, and key sentinels for global environmental change.

Platelets Restrict the Oxidative Burst in Phagocytes and Facilitate Primary Progressive Tuberculosis.

Rationale: Platelets are generated in the capillaries of the lung, control hemostasis, and display immunological functions. Tuberculosis primarily affects the lung, and patients show platelet changes and hemoptysis. A role of platelets in immunopathology of pulmonary tuberculosis requires careful assessment.Objectives: To identify the dynamics and interaction partners of platelets in the respiratory tissue and establish their impact on the outcome of pulmonary tuberculosis.Methods: Investigations were primarily performed in murine models of primary progressive pulmonary tuberculosis, by analysis of mouse strains with variable susceptibility to Mycobacterium tuberculosis infection using platelet depletion and delivery of antiplatelet drugs.Measurements and Main Results: Platelets were present at the site of infection and formed aggregates with different myeloid subsets during experimental tuberculosis. Such aggregates were also detected in patients with tuberculosis. Platelets were detrimental during the early phase of infection, and this effect was uncoupled from their canonical activation. Platelets left lung cell dynamics and patterns of antimycobacterial T-cell responses unchanged but hampered antimicrobial defense by restricting production of reactive oxygen species in lung-residing myeloid cells.Conclusions: Platelets are detrimental in primary progressive pulmonary tuberculosis, orchestrate lung immunity by modulating innate immune responsiveness, and may be amenable to new interventions for this deadly disease.

The quest for the genuine visual mismatch negativity (vMMN): Event-related potential indications of deviance detection for low-level visual features.

Research shows that the visual system monitors the environment for changes. For example, a left-tilted bar, a deviant, that appears after several presentations of a right-tilted bar, standards, elicits a classic visual mismatch negativity (vMMN): greater negativity for deviants than standards in event-related potentials (ERPs) between 100 and 300 ms after onset of the deviant. The classic vMMN is contributed to by adaptation; it can be distinguished from the genuine vMMN that, through use of control conditions, compares standards and deviants that are equally adapted and physically identical. To determine whether the vMMN follows similar principles to the auditory mismatch negativity (MMN), in two experiments we searched for a genuine vMMN from simple, physiologically plausible stimuli that change in fundamental dimensions: orientation, contrast, phase, and spatial frequency. We carefully controlled for attention and eye movements. We found no evidence for the genuine vMMN, despite adequate statistical power. We conclude that either the genuine vMMN is a rather unstable phenomenon that depends on still-to-be-identified experimental parameters, or it is confined to visual stimuli for which monitoring across time is more natural than monitoring over space, such as for high-level features. We also observed an early deviant-related positivity that we propose might reflect earlier predictive processing.

An Ocean-Colour Time Series for Use in Climate Studies: The Experience of the Ocean-Colour Climate Change Initiative (OC-CCI).

Ocean colour is recognised as an Essential Climate Variable (ECV) by the Global Climate Observing System (GCOS); and spectrally-resolved water-leaving radiances (or remote-sensing reflectances) in the visible domain, and chlorophyll-a concentration are identified as required ECV products. Time series of the products at the global scale and at high spatial resolution, derived from ocean-colour data, are key to studying the dynamics of phytoplankton at seasonal and inter-annual scales; their role in marine biogeochemistry; the global carbon cycle; the modulation of how phytoplankton distribute solar-induced heat in the upper layers of the ocean; and the response of the marine ecosystem to climate variability and change. However, generating a long time series of these products from ocean-colour data is not a trivial task: algorithms that are best suited for climate studies have to be selected from a number that are available for atmospheric correction of the satellite signal and for retrieval of chlorophyll-a concentration; since satellites have a finite life span, data from multiple sensors have to be merged to create a single time series, and any uncorrected inter-sensor biases could introduce artefacts in the series, e.g., different sensors monitor radiances at different wavebands such that producing a consistent time series of reflectances is not straightforward. Another requirement is that the products have to be validated against in situ observations. Furthermore, the uncertainties in the products have to be quantified, ideally on a pixel-by-pixel basis, to facilitate applications and interpretations that are consistent with the quality of the data. This paper outlines an approach that was adopted for generating an ocean-colour time series for climate studies, using data from the MERIS (MEdium spectral Resolution Imaging Spectrometer) sensor of the European Space Agency; the SeaWiFS (Sea-viewing Wide-Field-of-view Sensor) and MODIS-Aqua (Moderate-resolution Imaging Spectroradiometer-Aqua) sensors from the National Aeronautics and Space Administration (USA); and VIIRS (Visible and Infrared Imaging Radiometer Suite) from the National Oceanic and Atmospheric Administration (USA). The time series now covers the period from late 1997 to end of 2018. To ensure that the products meet, as well as possible, the requirements of the user community, marine-ecosystem modellers, and remote-sensing scientists were consulted at the outset on their immediate and longer-term requirements as well as on their expectations of ocean-colour data for use in climate research. Taking the user requirements into account, a series of objective criteria were established, against which available algorithms for processing ocean-colour data were evaluated and ranked. The algorithms that performed best with respect to the climate user requirements were selected to process data from the satellite sensors. Remote-sensing reflectance data from MODIS-Aqua, MERIS, and VIIRS were band-shifted to match the wavebands of SeaWiFS. Overlapping data were used to correct for mean biases between sensors at every pixel. The remote-sensing reflectance data derived from the sensors were merged, and the selected in-water algorithm was applied to the merged data to generate maps of chlorophyll concentration, inherent optical properties at SeaWiFS wavelengths, and the diffuse attenuation coefficient at 490 nm. The merged products were validated against in situ observations. The uncertainties established on the basis of comparisons with in situ data were combined with an optical classification of the remote-sensing reflectance data using a fuzzy-logic approach, and were used to generate uncertainties (root mean square difference and bias) for each product at each pixel.

Ceramides bind VDAC2 to trigger mitochondrial apoptosis.

Ceramides draw wide attention as tumor suppressor lipids that act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are largely unknown. Using a photoactivatable ceramide probe, we here identify the voltage-dependent anion channels VDAC1 and VDAC2 as mitochondrial ceramide binding proteins. Coarse-grain molecular dynamics simulations reveal that both channels harbor a ceramide binding site on one side of the barrel wall. This site includes a membrane-buried glutamate that mediates direct contact with the ceramide head group. Substitution or chemical modification of this residue abolishes photolabeling of both channels with the ceramide probe. Unlike VDAC1 removal, loss of VDAC2 or replacing its membrane-facing glutamate with glutamine renders human colon cancer cells largely resistant to ceramide-induced apoptosis. Collectively, our data support a role of VDAC2 as direct effector of ceramide-mediated cell death, providing a molecular framework for how ceramides exert their anti-neoplastic activity.

A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7.

Ceramides are central intermediates of sphingolipid metabolism with dual roles as mediators of cellular stress signaling and mitochondrial apoptosis. How ceramides exert their cytotoxic effects is unclear and their poor solubility in water hampers a search for specific protein interaction partners. Here, we report the application of a photoactivatable and clickable ceramide analog, pacCer, to identify ceramide binding proteins and unravel the structural basis by which these proteins recognize ceramide. Besides capturing ceramide transfer protein (CERT) from a complex proteome, our approach yielded CERT-related steroidogenic acute regulatory protein D7 (StarD7) as novel ceramide binding protein. Previous work revealed that StarD7 is required for efficient mitochondrial import of phosphatidylcholine (PC) and serves a critical role in mitochondrial function and morphology. Combining site-directed mutagenesis and photoaffinity labeling experiments, we demonstrate that the steroidogenic acute regulatory transfer domain of StarD7 harbors a common binding site for PC and ceramide. While StarD7 lacks robust ceramide transfer activity in vitro, we find that its ability to shuttle PC between model membranes is specifically affected by ceramides. Besides demonstrating the suitability of pacCer as a tool to hunt for ceramide binding proteins, our data point at StarD7 as a candidate effector protein by which ceramides may exert part of their mitochondria-mediated cytotoxic effects.

Type I IFN signaling triggers immunopathology in tuberculosis-susceptible mice by modulating lung phagocyte dynamics.

General interest in the biological functions of IFN type I in Mycobacterium tuberculosis (Mtb) infection increased after the recent identification of a distinct IFN gene expression signature in tuberculosis (TB) patients. Here, we demonstrate that TB-susceptible mice lacking the receptor for IFN I (IFNAR1) were protected from death upon aerogenic infection with Mtb. Using this experimental model to mimic primary progressive pulmonary TB, we dissected the immune processes affected by IFN I. IFNAR1 signaling did not affect T-cell responses, but markedly altered migration of inflammatory monocytes and neutrophils to the lung. This process was orchestrated by IFNAR1 expressed on both immune and tissue-resident radioresistant cells. IFNAR1-driven TB susceptibility was initiated by augmented Mtb replication and in situ death events, along with CXCL5/CXCL1-driven accumulation of neutrophils in alveoli, followed by the discrete compartmentalization of Mtb in lung phagocytes. Early depletion of neutrophils rescued TB-susceptible mice to levels observed in mice lacking IFNAR1. We conclude that IFN I alters early innate events at the site of Mtb invasion leading to fatal immunopathology. These data furnish a mechanistic explanation for the detrimental role of IFN I in pulmonary TB and form a basis for understanding the complex roles of IFN I in chronic inflammation.

MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment.

The molecular mechanisms that control innate immune cell trafficking during chronic infection and inflammation, such as in tuberculosis (TB), are incompletely understood. During active TB, myeloid cells infiltrate the lung and sustain local inflammation. While the chemoattractants that orchestrate these processes are increasingly recognized, the posttranscriptional events that dictate their availability are unclear. We identified microRNA-223 (miR-223) as an upregulated small noncoding RNA in blood and lung parenchyma of TB patients and during murine TB. Deletion of miR-223 rendered TB-resistant mice highly susceptible to acute lung infection. The lethality of miR-223(­/­) mice was apparently not due to defects in antimycobacterial T cell responses. Exacerbated TB in miR-223(­/­) animals could be partially reversed by neutralization of CXCL2, CCL3, and IL-6, by mAb depletion of neutrophils, and by genetic deletion of Cxcr2. We found that miR-223 controlled lung recruitment of myeloid cells, and consequently, neutrophil-driven lethal inflammation. We conclude that miR-223 directly targets the chemoattractants CXCL2, CCL3, and IL-6 in myeloid cells. Our study not only reveals an essential role for a single miRNA in TB, it also identifies new targets for, and assigns biological functions to, miR-223. By regulating leukocyte chemotaxis via chemoattractants, miR-223 is critical for the control of TB and potentially other chronic inflammatory diseases.

Object-related regularities are processed automatically: evidence from the visual mismatch negativity.

One of the most challenging tasks of our visual systems is to structure and integrate the enormous amount of incoming information into distinct coherent objects. It is an ongoing debate whether or not the formation of visual objects requires attention. Implicit behavioral measures suggest that object formation can occur for task-irrelevant and unattended visual stimuli. The present study investigated pre-attentive visual object formation by combining implicit behavioral measures and an electrophysiological indicator of pre-attentive visual irregularity detection, the visual mismatch negativity (vMMN) of the event-related potential. Our displays consisted of two symmetrically arranged, task-irrelevant ellipses, the objects. In addition, there were two discs of either high or low luminance presented on the objects, which served as targets. Participants had to indicate whether the targets were of the same or different luminance. In separate conditions, the targets either usually were enclosed in the same object or in two different objects (standards). Occasionally, the regular target-to-object assignment was changed (deviants). That is, standards and deviants were exclusively defined on the basis of the task-irrelevant target-to-object assignment but not on the basis of some feature regularity. Although participants did not notice the regularity nor the occurrence of the deviation in the sequences, task-irrelevant deviations resulted in increased reaction times. Moreover, compared with physically identical standard displays deviating target-to-object assignments elicited a negative potential in the 246-280 ms time window over posterio-temporal electrode positions which was identified as vMMN. With variable resolution electromagnetic tomography (VARETA) object-related vMMN was localized to the inferior temporal gyrus. Our results support the notion that the visual system automatically structures even task-irrelevant aspects of the incoming information into objects.

Impact of lower- vs. upper-hemifield presentation on automatic colour-deviance detection: a visual mismatch negativity study.

The automatic processing of deviances from the temporal context of the visual environment has become an important topic in visual cognitive sciences, which is often investigated using the visual mismatch negativity (vMMN). This event-related potential (ERP) component is elicited by an irregular stimulus (e.g., a red disc) presented in a series of stimuli (e.g., green discs) comprising a temporal regularity (e.g., colour repetition). We determined the influence of lower- vs. upper-hemifield presentation of the irregular stimulus on the vMMN while using whole-field stimulus displays controlling for sustained shifts in spatial attention. Deviances presented in the lower hemifield elicited a larger vMMN than the ones presented in the upper hemifield at a latency of 200-280ms. However, this asymmetry was preceded by deviance-related hemifield effects already emerging at an earlier latency (110-150ms), where upper-hemifield deviances elicited a positive potential but lower-hemifield deviances did not. With variable resolution electromagnetic tomography (VARETA) early deviance-related activity was localised to retinotopically organised regions of the visual cortex (BA 17/18) and vMMN-sources were localised to the middle/superior occipital gyrus, to higher areas along the temporal visual stream, but also to BA 17/18. We argue that the upper/lower-hemifield vMMN asymmetry relies at least partially on the hemifield-dependent differential sensitivity of early deviance-related activity generated in retinotopically organised regions of the visual cortex. However, a superior automatic processing of deviances presented in the lower visual hemifield may also contribute to the effect.

Which kind of transition is important for sound representation? An event-related potential study.

Auditory transients (such as sound onset or a frequency transition within a continuous sound) are assumed to parse the auditory input into smaller units enabling the formation of unitary sound representations separately for each segment. This was discovered by using the mismatch negativity (MMN) component of the event-related potential (ERP) that taps into auditory sensory memory representations. For unstructured sounds, MMN amplitude decreased or even vanished with increasing the temporal distance of an irregular feature (deviance, e.g. duration decrement) relative to the onset of an otherwise regularly occurring sound, whereas for sounds that were segmented by a transient, MMN persisted. It has been speculated that the P1-N1-P2 complex, indexing the sensory encoding of the transient, determines the temporal units of the acoustic input that are represented by the information processing system. To test this hypothesis, we utilized a previously reported asymmetry in the sensory encoding of physically identical but time-reversed transitions between segments of constant and gliding frequency. In separate blocks, we regularly presented 1400-ms sounds with a centered constant-to-glide or glide-to-constant transition. Occasionally and unpredictably, one of the regularly occurring sounds was shortened in duration to 910 ms. We found larger transition-related P1-N1-P2 potentials accompanied by larger deviance-related MMN amplitudes for sounds with constant-to-glide transition than for sounds with glide-to-constant transition. This provides evidence that it is the precise sensory encoding of the transition which is crucial for automatically parsing the auditory input into smaller units, thus enabling the formation of unitary sound representations even for late segments.

Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis.

As a hallmark of tuberculosis (TB), Mycobacterium tuberculosis (MTB) induces granulomatous lung lesions and systemic inflammatory responses during active disease. Molecular regulation of inflammation is associated with inflammasome assembly. We determined the extent to which MTB triggers inflammasome activation and how this impacts on the severity of TB in a mouse model. MTB stimulated release of mature IL-1ß in macrophages while attenuated M. bovis BCG failed to do so. Tubercle bacilli specifically activated the NLRP3 inflammasome and this propensity was strictly controlled by the virulence-associated RD1 locus of MTB. However, Nlrp3-deficient mice controlled pulmonary TB, a feature correlated with NLRP3-independent production of IL-1ß in infected lungs. Our studies demonstrate that MTB activates the NLRP3 inflammasome in macrophages in an ESX-1-dependent manner. However, during TB, MTB promotes NLRP3- and caspase-1-independent IL-1ß release in myeloid cells recruited to lung parenchyma and thus overcomes NLRP3 deficiency in vivo in experimental models.

Carbohydrate restricted diet in conjunction with metformin and liraglutide is an effective treatment in patients with deteriorated type 2 diabetes mellitus: Proof-of-concept study.

BACKGROUND: Type 2 diabetes mellitus is a chronic progressive disease. During the course of the disease intensive treatment is often necessary resulting in multiple interventions including administration of insulin. Although dietary intervention is highly recommended, the clinical results of the widely prescribed diets with low fat content and high carbohydrates are disappointing. In this proof-of-concept study, we tested the effect of dietary carbohydrate-restriction in conjunction with metformin and liraglutide on metabolic control in patients with type 2 diabetes. METHODS: Forty patients with type 2 diabetes already being treated with two oral anti-diabetic drugs or insulin treatment and who showed deterioration of their glucose metabolism (i.e. HbA1c >7.5), were treated. A carbohydrate-restricted diet and a combination of metformin and liraglutide were instituted, after stopping either insulin or oral anti-diabetic drugs (excluding metformin). After enrollment, the study patients were scheduled for follow-up visits at one, two, three and six months. Primary outcome was glycemic control, measured by HbA1c at six months. Secondary outcomes were body weight, lipid-profile and treatment satisfaction. RESULTS: Thirty-five (88%) participants completed the study. Nearly all participating patients experienced a drop in HbA1c and body weight during the first three months, an effect which was maintained until the end of the study at six months. Seventy-one percent of the patients reached HbA1c values below 7.0%. The range of body weight at enrollment was extreme, reaching 165 kg as the highest initial value. The average weight loss after 6 months was 10%. Most patients were satisfied with this treatment. During the intervention no significant change of lipids was observed. Most patients who were on insulin could maintain the treatment without insulin with far better metabolic control. CONCLUSIONS: Carbohydrate restriction in conjunction with metformin and liraglutide is an effective treatment option for patients with advanced diabetes who are candidates for instituting insulin or who are in need of intensified insulin treatment. This proof-of-principle study showed a significant treatment effect on metabolic control.

Omission mismatch negativity builds up late.

The mismatch negativity (MMN) event-related potential (ERP) is elicited by irregular sounds in a regular sound sequence. MMN depends on the length of the preceding regular stimulation: in repetitive sequences, changes following only two or three repetitions may elicit MMN. Thus, MMN builds up rapidly. Infrequent omissions in a repetitive sound sequence may also elicit an MMN-like waveform. In this study, the build-up of this omission-related ERP was investigated. Trains of two to nine tones with omissions at the penultimate stimulus positions were presented. Results showed no consistent omission-related ERP. In contrast, when omissions occurred with 9% probability among continuously presented tones, the omission-related waveform was elicited. Thus, the omission-related ERP builds up later than MMN.

A temporal constraint for automatic deviance detection and object formation: A mismatch negativity study.

The automatic detection of deviations within a constant sine wave tone is confined to the initial part of approximately 350 ms. When a deviation occurs beyond this critical limit, the mismatch negativity (MMN) - a deviance-related component of the event-related potential - is largely attenuated or even absent. However, for time-variant acoustic stimuli such as speech sounds or tonal patterns, MMN is also obtained for deviations beyond the initial 350 ms. We consider two hypotheses that can explain the MMN to time-variant sounds. One is that the terminal part of those sounds is represented as the spectral information varies over time (spectral-variation hypothesis). The other is that transients, occurring in time-variant signals, help to segment the long sounds into smaller units, each being not larger than the critical 350 ms (segmentation hypothesis). We measured MMN to duration shortenings (deviants) embedded in a sequence of 1000 ms long standard tones of increasing frequency (sweeps). The sweeps did or did not contain a noise burst. Results reveal a lack of MMN to the duration deviant in the sweep without a noise burst, which rules out the spectral-variation hypothesis. The presence of MMN to the duration deviant in the sweep with a noise burst supports the segmentation hypothesis. Thus, the results suggest a temporal constraint inherent to the processing of unstructured/unsegmented long tones. We argue that transients within a sound act as segmentation cues providing an automatic sound representation for which deviations can be detected.

Visual object representations can be formed outside the focus of voluntary attention: evidence from event-related brain potentials.

There is an ongoing debate whether visual object representations can be formed outside the focus of voluntary attention. Recently, implicit behavioral measures suggested that grouping processes can occur for task-irrelevant visual stimuli, thus supporting theories of preattentive object formation (e.g., Lamy, D., Segal, H., & Ruderman, L. Grouping does not require attention. Perception and Psychophysics, 68, 17-31, 2006; Russell, C., & Driver, J. New indirect measures of "inattentive" visual grouping in a change-detection task. Perception and Psychophysics, 67, 606-623, 2005). We developed an ERP paradigm that allows testing for visual grouping when neither the objects nor its constituents are related to the participant's task. Our paradigm is based on the visual mismatch negativity ERP component, which is elicited by stimuli deviating from a regular stimulus sequence even when the stimuli are ignored. Our stimuli consisted of four pairs of colored discs that served as objects. These objects were presented isochronously while participants were engaged in a task related to the continuously presented fixation cross. Occasionally, two color deviances occurred simultaneously either within the same object or across two different objects. We found significant ERP differences for same- versus different-object deviances, supporting the notion that forming visual object representations by grouping can occur outside the focus of voluntary attention. Also our behavioral experiment, in which participants responded to color deviances--thus, this time the discs but, again, not the objects were task relevant--showed that the object status matters. Our results stress the importance of early grouping processes for structuring the perceptual world.

Disentangling effects of auditory distraction and of stimulus-response sequence.

When we pay attention to one task, irrelevant changes may interfere. The effect of changes on behavioral and electrophysiological responses has been studied in two separate research fields: Research on Distraction states that a rare irrelevant change takes attention away from the primary task. Research on Sequences states that any change in stimulus or response incurs a cost or benefit depending on the kind of change. To disentangle distraction from sequence effects, we made task-irrelevant changes rare in one condition and frequent in another while also assessing stimulus and response changes from trial to trial. Participants used key presses to classify syllables presented in two different, irrelevant voice pitches. We found that distraction and sequence interacted to alter reaction times and errors on the primary task and also to alter ERP markers of distraction (P3a). The sequential effects cannot, however, fully account for distraction.

Differential processing of terminal tone parts within structured and non-structured tones.

Recent studies utilizing the mismatch negativity (MMN) event-related potential (ERP) revealed that when a repetitive sequence of sinusoidal tones is presented, the occasional insertion of a short deviation into some of the tones leads to the elicitation of an MMN only if it occurs during the initial 300 ms, but not beyond. In contrast, deviations occurring in speech sounds elicit MMN even beyond 300 ms. We conducted two experiments to resolve this conflict. We hypothesised that an additional transient within an otherwise unstructured tone may overcome this limitation. First, we tested for MMN to a deviance at the terminal part of a 650 ms tone which did or did not contain a gap. Only when the tone included the gap, MMN was obtained. Second, we compared the gap condition with two noise conditions, in which the gap was replaced by modulated white noise. The noise conditions differed with respect to the saliency of the perceived interruption of the tone. In all three conditions, MMN was elicited. These results demonstrate that structuring a sinusoidal tone by a gap or a noise interval is sufficient to regain MMN. It is suggested that the introduction of an additional transient triggers a new integration window overcoming the temporal constraints of automatic tone representation. This resolves the seeming contradiction between MMN studies using tonal and speech sounds.

Temporal grouping affects the automatic processing of deviant sounds.

The present study investigates the influence of auditory temporal grouping on automatic sound processing. We compared the mismatch negativity (MMN) event-related potential elicited by successive deviant tones in a condition in which sounds were organized in tone pairs with respective MMN obtained in a non-paired sequence. When successive deviants belonged to different tone pairs the second deviant elicited a higher MMN amplitude than the corresponding deviant in the non-paired condition. Moreover, this temporal grouping had immediate effects on the extraction of rules as revealed by the finding that first and single deviants at the second position of a tone pair elicited larger MMNs than corresponding deviants in the non-paired condition or first and single deviants at the first position of a tone pair. Results demonstrate that auditory objects generated by temporal proximity are treated as relatively encapsulated units and that automatic deviance-detection may rely on multiple hierarchically organized representations of sound sequences.