A mismatch negativity study of local-global auditory processing.
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We used mismatch negativity (MMN) to examine structural encoding of local and global auditory patterns in perceptual memory. Unlike previous MMN studies of local-global auditory perceptual organization that used interval-contour stimuli, here we presented hierarchical stimuli in which local pattern organization formed global patterns. Importantly, our stimuli allowed independent manipulation of the two structural levels. In separate blocks, participants were exposed to frequent local standard patterns and rare local deviant patterns, or to frequent global standard patterns and rare global deviant patterns. Within each deviant pattern, the variation from the standard pattern could occur at onset (early), towards the end of the pattern (late) or over both time windows (both). To isolate pattern indexing at one level, the other level continuously changed (e.g., in a global standard block, local elements varied trial-by-trial). MMN was found only for global deviant patterns, and only when deviation occurred late in the pattern. In a separate behavioral experiment, global deviants were detected more often than local ones, although initial similarity followed by a late deviation from the standard pattern was not required for explicit deviant detection (as with the MMN). This report demonstrates neural structural encoding for global information, when independently manipulated from local information. Furthermore, it extends previous MMN findings that have revealed indexing of complex abstract auditory information to the realm of hierarchical perceptual organization. (+info)
Hippocampal event-related potentials to tone duration deviance in a passive oddball paradigm in humans.
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The mismatch negativity (MMN), a component of event-related potentials (ERPs), is assumed to reflect a preattentive auditory discrimination process. Although an involvement of hippocampal structures in deviance detection was shown in animal experiments, invasive recordings in humans have not been able to provide such an evidence so far. In the current study, ERPs were recorded from intrahippocampal and scalp electrodes in 16 epilepsy patients. Stimulation consisted of trains of six tones, with one tone deviating in duration (100 vs. 50 ms). In the rhinal cortex, ERPs elicited by deviants were larger in amplitude than those of standards (around 200 ms). The rhinal activation was succeeded by a long-lasting hippocampal ERP component (around 350 ms). However, in contrast to the rhinal activation, hippocampal activation was also elicited by the 1st stimuli of the train and might, therefore, be related more to salience detection than to deviance detection. The current study provides evidence that the MMN is part of a multistage comparison process and that the rhinal cortex is part of its underlying cortical network. (+info)
Neural responses to auditory stimulus deviance under threat of electric shock revealed by spatially-filtered magnetoencephalography.
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Stimulus novelty or deviance may be especially salient in anxiety-related states due to sensitization to environmental change, a key symptom of anxiety disorders such as posttraumatic stress disorder (PTSD). We aimed to identify human brain regions that show potentiated responses to stimulus deviance during anticipatory anxiety. Twenty participants (14 men) were presented a passive oddball auditory task in which they were exposed to uniform auditory stimulation of tones with occasional deviations in tone frequency, a procedure that elicits the mismatch negativity (MMN) and its magnetic counterpart (MMNm). These stimuli were presented during threat periods when participants anticipated unpleasant electric shocks, and safe periods when no shocks were anticipated. Neuromagnetic data were collected with a 275-channel whole-head MEG system and event-related beamformer analyses were conducted to estimate source power across the brain in response to stimulus deviance. Source analyses revealed greater right auditory and inferior parietal activity to stimulus deviance under threat relative to safe conditions, consistent with locations of MMN and MMNm sources identified in other studies. Structures related to evaluation of threat, left amygdala and right insula, also showed increased activity to stimulus deviance under threat. As anxiety level increased across participants, right and left auditory cortical as well as right amygdala activity increased to stimulus deviance. These findings fit with evidence of a potentiated MMN in PTSD relative to healthy controls, and warrant closer evaluation of how these structures might form a functional network mediating sensitization to stimulus deviance during anticipatory anxiety. (+info)
Learning-related changes in brain activity following errors and performance feedback in schizophrenia.
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In previous studies of self-monitoring in schizophrenia, patients have exhibited reductions in the amplitude of the error-related negativity (ERN), a component of the event-related brain potential (ERP) elicited most prominently immediately following the execution of incorrect responses. In the current study, we examined the ERN and a related component, the feedback negativity (FBN) in 26 schizophrenia outpatients and 27 psychiatrically healthy comparison subjects during a probabilistic learning task in which participants could learn stimulus-response pairs by attending to feedback indicating response accuracy. The validity of the feedback varied in three conditions. In one condition, accuracy feedback was entirely consistent (i.e., a left response to one of the stimuli in this condition was always correct and a right response was always incorrect). In the second condition, feedback was valid on only 80% of the trials, and in the third condition, accuracy feedback was random. Changes in ERP amplitudes accompanying learning of stimulus-response pairs were examined. Schizophrenia patients exhibited reduced ERN amplitude compared to healthy subjects in all conditions. This finding extends the previously reported impairment to include disruption of self-monitoring on a task in which participants learn stimulus-response mappings by trial and error, rather than being told the mappings explicitly. Schizophrenia patients also exhibited reduced FBN amplitude compared to healthy subjects in the 100% condition during early trials when the feedback was essential for accurate performance. These findings suggest that reward-related brain activity is weakened in schizophrenia, perhaps reflecting diminished sensitivity to whether ongoing events are better or worse than expected. (+info)
Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients.
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In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2 g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia. (+info)
Anticipation of affect in dysthymia: behavioral and neurophysiological indicators.
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Anticipation for future affective events and prediction uncertainty were examined in healthy controls and individuals with dysthymia (DYS) using behavioral responses and the contingent negative variation (CNV) and post-imperative negative variation (PINV) event-related potential (ERP) components. Warning stimuli forecasted the valence of subsequently presented adjectives ("+", positive; "=", neutral; "-", negative), and participants indicated whether each adjective would describe them over the next two weeks. Controls expected fewer negative, and individuals with DYS expected fewer positive, adjectives to apply to them. CNV amplitudes were enhanced in controls prior to positive versus other adjectives. Response times and PINV amplitudes were greater following neutral compared to other adjectives, and PINV was larger overall in dysthymics compared to controls. In sum, healthy controls and individuals with DYS exhibit different behavioral and neurophysiological biases in anticipation for future affective events. These results are discussed in the context of cognitive theories of depression. (+info)
Spatiotemporal dynamics of error processing dysfunctions in major depressive disorder.
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