Frontal and temporal sources of mismatch negativity in healthy controls, patients at onset of schizophrenia in adolescence and others at 15 years after onset

Mismatch negativity (MMN) is an event-related potential measure of auditory change detection. It is widely reported to be smaller in patients with schizophrenia and may not improve along with otherwise successful clinical treatment. The main aim of this report is to explore ways of measuring and presenting four features of frequency-deviant MMN dipole sources (dipole moment, peak latency, brain location and orientation) and to relate these to the processes of psychopathology and illness progression. Data from early onset patients (EOS) at the start of the illness in adolescence, and others who had their first break in adolescence 15 years ago (S-15Y) were compared with two groups of age-matched healthy controls (C-EOS, C-15Y). A four-source model fitted the MMN waveform recorded from all four groups, whether MMN amplitude was more (EOS) or less (S-15Y) reduced. The locations were in the left superior temporal and anterior cingulate gyri, right superior temporal and inferior/mid frontal cortices. Dipole latencies confirmed a bottom-up sequence of processing and dipole moments were larger in the temporal lobes and on the left. Patients showed small dipole location changes that were more marked in the S-15Y than the EOS group (more rostral for the left anterior cingulate, more caudal for the right mid-frontal dipole) consistent with illness progression. The modelling of MMN dipole sources on brain atlas and anatomical images suggests that there is a degree of dissociation during illness between small progressive anatomical changes and some functional recovery indexed by scalp recordings from patients with an onset in adolescence 15 years before compared to adolescents in their first episode. © 2004 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex

Oscillation encoding of individual differences in speech perception

Individual differences in second language (L2) phoneme perception (within the normal population) have been related to/nspeech perception abilities, also observed in the native language, in studies assessing the electrophysiological response/nmismatch negativity (MMN). Here, we investigate the brain oscillatory dynamics in the theta band, the spectral correlate of/nthe MMN, that underpin success in phoneme learning. Using previous data obtained in an MMN paradigm, the dynamics of/ncortical oscillations while perceiving native and unknown phonemes and nonlinguistic stimuli were studied in two groups/nof participants classified as good and poor perceivers (GPs and PPs), according to their L2 phoneme discrimination abilities./nThe results showed that for GPs, as compared to PPs, processing of a native phoneme change produced a significant/nincrease in theta power. Stimulus time-locked analysis event-related spectral perturbation (ERSP) showed differences for the/ntheta band within the MMN time window (between 70 and 240 ms) for the native deviant phoneme. No other significant/ndifference between the two groups was observed for the other phoneme or nonlinguistic stimuli. The dynamic patterns in/nthe theta-band may reflect early automatic change detection for familiar speech sounds in the brain. The behavioral/ndifferences between the two groups may reflect individual variations in activating brain circuits at a perceptual level.This research was supported by grants from the European Community’s Seventh Framework Programme (FP7/2007–2013): ERG grant agreement number 323961, the Spanish Ministerio de Economía y Competitividad (PSI 2012 - 34071), and the Catalan Government (SGR 2009-1521) to N. Sebastián-Gallés, and the People Programme (Marie Curie Actions) of the European Union’sSeventh Framework Programme (FP7/2007–2013) under REA grant agreement n° 328671 to B. Díaz. N. Sebastián-Gallés received the “ICREA Acadèmia” Prize for Excellence in Research, funded by the Generalitat de Catalunya. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Auditory change detection in schizophrenia: sources of activity, related neuropsychological function and symptoms in patients with a first episode in adolescence, and patients 14 years after an adolescent illness-onset

<p>Abstract</p> <p>Background</p> <p>The event-related brain response mismatch negativity (MMN) registers changes in auditory stimulation with temporal lobe sources reflecting short-term echoic memory and frontal sources a deviance-induced switch in processing. Impairment, controversially present at the onset of schizophrenia, develops rapidly and can remain independent of clinical improvement. We examined the characteristics of the scalp-recorded MMN and related these to tests of short-term memory and set-shifting. We assessed whether the equivalent dipole sources are affected already at illness-onset in adolescence and how these features differ after a 14-year course following an adolescent onset. The strength, latency, orientation and location of frontal and temporal lobe sources of MMN activity early and late in the course of adolescent-onset schizophrenia are analysed and illustrated.</p> <p>Methods</p> <p>MMN, a measure of auditory change-detection, was elicited by short deviant tones in a 3-tone oddball-presentation and recorded from 32 scalp electrodes. Four dipole sources were placed following hypothesis-led calculations using brain electrical source analysis on brain atlas and MR-images. A short neuropsychological test battery was administered. We compared 28 adolescent patients with a first episode of schizophrenia and 18 patients 14 years after diagnosis in adolescence with two age-matched control groups from the community (n = 22 and 18, respectively).</p> <p>Results</p> <p>MMN peaked earlier in the younger than the older subjects. The amplitude was reduced in patients, especially the younger group, and was here associated with negative symptoms and slow set-shifting. In first-episode patients the temporal lobe sources were more ventral than in controls, while the left cingular and right inferior-mid frontal sources were more caudal. In the older patients the left temporal locus remained ventral (developmental stasis), the right temporal locus extended more antero-laterally (illness progression), and the right frontal source moved antero-laterally (normalised).</p> <p>Conclusion</p> <p>From the start of the illness there were differences in the dipole-model between healthy and patient groups. Separate characteristics of the sources of the activity differences showed an improvement, stasis or deterioration with illness-duration. The precise nature of the changes in the sources of MMN activity and their relationship to selective information processing and storage depend on the specific psychopathology and heterogeneous course of the illness.</p

Trait aspects of auditory mismatch negativity predict response to auditory training in individuals with early illness schizophrenia

BackgroundIndividuals with schizophrenia have heterogeneous impairments of the auditory processing system that likely mediate differences in the cognitive gains induced by auditory training (AT). Mismatch negativity (MMN) is an event-related potential component reflecting auditory echoic memory, and its amplitude reduction in schizophrenia has been linked to cognitive deficits. Therefore, MMN may predict response to AT and identify individuals with schizophrenia who have the most to gain from AT. Furthermore, to the extent that AT strengthens auditory deviance processing, MMN may also serve as a readout of the underlying changes in the auditory system induced by AT.MethodsFifty-six individuals early in the course of a schizophrenia-spectrum illness (ESZ) were randomly assigned to 40 h of AT or Computer Games (CG). Cognitive assessments and EEG recordings during a multi-deviant MMN paradigm were obtained before and after AT and CG. Changes in these measures were compared between the treatment groups. Baseline and trait-like MMN data were evaluated as predictors of treatment response. MMN data collected with the same paradigm from a sample of Healthy Controls (HC; n = 105) were compared to baseline MMN data from the ESZ group.ResultsCompared to HC, ESZ individuals showed significant MMN reductions at baseline (p = .003). Reduced Double-Deviant MMN was associated with greater general cognitive impairment in ESZ individuals (p = .020). Neither ESZ intervention group showed significant change in MMN. We found high correlations in all MMN deviant types (rs = .59-.68, all ps &lt; .001) between baseline and post-intervention amplitudes irrespective of treatment group, suggesting trait-like stability of the MMN signal. Greater deficits in trait-like Double-Deviant MMN predicted greater cognitive improvements in the AT group (p = .02), but not in the CG group.ConclusionsIn this sample of ESZ individuals, AT had no effect on auditory deviance processing as assessed by MMN. In ESZ individuals, baseline MMN was significantly reduced relative to HCs, and associated with global cognitive impairment. MMN did not show changes after AT and exhibited trait-like stability. Greater deficits in the trait aspects of Double-Deviant MMN predicted greater gains in global cognition in response to AT, suggesting that MMN may identify individuals who stand to gain the most from AT.Trial registrationNCT00694889. Registered 1 August 2007

Gradient sensing in defined chemotactic fields

Cells respond to a variety of secreted molecules by modifying their physiology, growth patterns, and behavior. Motile bacteria and eukaryotic cells can sense extracellular chemoattractants and chemorepellents and alter their movement. In this way fibroblasts and leukocytes can find their ways to sites of injury and cancer cells can home in on sites that are releasing growth factors. Social amoebae such as Dictyostelium are chemotactic to cAMP which they secrete several hours after they have initiated development. These eukaryotic cells are known to be able to sense extremely shallow gradients but the processes underlying their exquisite sensitivity are still largely unknown. In this study we determine the responses of developed cells of Dictyostelium discoideum to stable linear gradients of cAMP of varying steepness generated in 2 µm deep gradient chambers of microfluidic devices. The gradients are generated by molecular diffusion between two 50 µm deep flow-through channels, one of which is perfused with a solution of cAMP and the other with buffer, serving as continuously replenished source and sink. These low ceiling gradient chambers constrained the cells in the vertical dimension, facilitatin