Auditory Event-related Brain Potentials Research Articles

Effects of the cardiac cycle on auditory processing: A preregistered study on mismatch negativity.

The systolic and diastolic phases of the cardiac cycle are known to affect perception and cognition differently. Higher order processing tends to be facilitated at systole, whereas sensory processing of external stimuli tends to be impaired at systole compared to diastole. The current study aims to examine whether the cardiac cycle affects auditory deviance detection, as reflected in the mismatch negativity (MMN) of the event-related brain potential (ERP). We recorded the intensity deviance response to deviant tones (70 dB) presented among standard tones (60 or 80 dB, depending on blocks) and calculated the MMN by subtracting standard ERP waveforms from deviant ERP waveforms. We also assessed intensity-dependent N1 and P2 amplitude changes by subtracting ERPs elicited by soft standard tones (60 dB) from ERPs elicited by loud standard tones (80 dB). These subtraction methods were used to eliminate phase-locked cardiac-related electric artifacts that overlap auditory ERPs. The endogenous MMN was expected to be larger at systole, reflecting the facilitation of memory-based auditory deviance detection, whereas the exogenous N1 and P2 would be smaller at systole, reflecting impaired exteroceptive sensory processing. However, after the elimination of cardiac-related artifacts, there were no significant differences between systole and diastole in any ERP components. The intensity-dependent N1 and P2 amplitude changes were not obvious in either cardiac phase, probably because of the short interstimulus intervals. The lack of a cardiac phase effect on MMN amplitude suggests that preattentive auditory processing may not be affected by bodily signals from the heart.

Effects of iron supplementation on neural indices of habituation in Bangladeshi children

BackgroundIron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear. ObjectiveWe aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs). MethodsThis substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12. ResultsData were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07μV [95% CI: −1.22, 1.37]; MNPs compared with placebo: MD = 0.58μV [95% CI: −0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy. ConclusionIn Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation.This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.

Impact of brain overgrowth on sensorial learning processing during the first year of life.

Macrocephaly is present in about 2–5% of the general population. It can be found as an isolated benign trait or as part of a syndromic condition. Brain overgrowth has been associated with neurodevelopmental disorders such as autism during the first year of life, however, evidence remains inconclusive. Furthermore, most of the studies have involved pathological or high-risk populations, but little is known about the effects of brain overgrowth on neurodevelopment in otherwise neurotypical infants. We investigated the impact of brain overgrowth on basic perceptual learning processes (repetition effects and change detection response) during the first year of life. We recorded high density electroencephalograms (EEG) in 116 full-term healthy infants aged between 3 and 11 months, 35 macrocephalic (14 girls) and 81 normocephalic (39 girls) classified according to the WHO head circumference norms. We used an adapted oddball paradigm, time-frequency analyses, and auditory event-related brain potentials (ERPs) to investigate differences between groups. We show that brain overgrowth has a significant impact on repetition effects and change detection response in the 10–20 Hz frequency band, and in N450 latency, suggesting that these correlates of sensorial learning processes are sensitive to brain overgrowth during the first year of life.

A Multimodal Neuroprosthetic Interface to Record, Modulate and Classify Electrophysiological Biomarkers Relevant to Neuropsychiatric Disorders.

Most mental disorders, such as addictive diseases or schizophrenia, are characterized by impaired cognitive function and behavior control originating from disturbances within prefrontal neural networks. Their often chronic reoccurring nature and the lack of efficient therapies necessitate the development of new treatment strategies. Brain-computer interfaces, equipped with multiple sensing and stimulation abilities, offer a new toolbox whose suitability for diagnosis and therapy of mental disorders has not yet been explored. This study, therefore, aimed to develop a biocompatible and multimodal neuroprosthesis to measure and modulate prefrontal neurophysiological features of neuropsychiatric symptoms. We used a 3D-printing technology to rapidly prototype customized bioelectronic implants through robot-controlled deposition of soft silicones and a conductive platinum ink. We implanted the device epidurally above the medial prefrontal cortex of rats and obtained auditory event-related brain potentials in treatment-naïve animals, after alcohol administration and following neuromodulation through implant-driven electrical brain stimulation and cortical delivery of the anti-relapse medication naltrexone. Towards smart neuroprosthetic interfaces, we furthermore developed machine learning algorithms to autonomously classify treatment effects within the neural recordings. The neuroprosthesis successfully captured neural activity patterns reflecting intact stimulus processing and alcohol-induced neural depression. Moreover, implant-driven electrical and pharmacological stimulation enabled successful enhancement of neural activity. A machine learning approach based on stepwise linear discriminant analysis was able to deal with sparsity in the data and distinguished treatments with high accuracy. Our work demonstrates the feasibility of multimodal bioelectronic systems to monitor, modulate and identify healthy and affected brain states with potential use in a personalized and optimized therapy of neuropsychiatric disorders.

Effects of Supplementation With Iron Syrup or Iron-Containing Multiple Micronutrient Powders on Neural Indices of Cognitive Functioning in Bangladeshi Children

ObjectivesMicronutrients, especially iron, play a critical role in the developing infant brain. Yet, the causal effects of iron supplementation on neurocognitive functioning in a low-income anemic population of children have not been examined. This study sought to evaluate the effects of supplementation with iron syrup and iron-containing multiple micronutrient powders (MNPs) in Bangladeshi children on habituation to familiar sounds, a marker for healthy memory development, using auditory event-related brain potentials (ERPs). MethodsThis study was nested within the Benefits and Risks of Iron Supplementation in Children (BRISC) trial, a double blinded double dummy randomized controlled trial (RCT). At 8 months of age, 3300 children were randomized to receive 3 months of 1) iron syrup + placebo MNPs, or 2) MNPs (containing iron, retinol, zinc, and Vitamin C) + placebo iron syrup, or 3) placebo iron syrup and placebo MNPs. ERPs in response to an auditory roving oddball paradigm were measured in a random subset of 441 children at 3 months post-intervention (11 months of age) and 595 children after a further 9 months follow-up (20 months of age). ERP measures indexing aspects of habituation included the [deviant minus standard] difference waveform amplitude, N2 waveform amplitude, and the difference in deviant-evoked ERP amplitudes between the first and second half of the paradigm. Intention-to-treat analyses on ERP outcomes using linear models were used at 11 and 20 months of age separately. ResultsBaseline characteristics were balanced between treatment groups. Overall prevalence of anemia was 43.7% and iron deficiency was 28.4%. Intention-to-treat analyses indicated no significant treatment effects of iron or MNPs on the difference waveform amplitude at 11 months of age [mean difference (MD, 95% CI) iron vs placebo 0.24 (–1.03, 1.51); MNP vs placebo 0.59 (–0.70, 1.88)] and 20 months of age [(MD, 95% CI) iron vs placebo 0.50 (–0.62, 1.63); MNP vs placebo 0.24 (–0.89, 1.38)]. There were no differences by treatment arm for the other ERP measures. ConclusionsResults from a rigorous prospectively powered sub-study of an RCT in an iron deficient population indicated no significant effects of supplementation with iron or MNPs on neural indices of habituation. Funding SourcesNHMRC and The University of Melbourne.

Effects of Hyperbaric Nitrogen Narcosis on Cognitive Performance in Recreational air SCUBA Divers: An Auditory Event-related Brain Potentials Study.

The narcotic effect of hyperbaric nitrogen is most pronounced in air-breathing divers because it impairs diver's cognitive and behavioral performance, and limits the depth of dive profiles. We aimed to investigate the cognitive effects of simulated (500 kPa) air environments in recreational SCUBA divers, revealed by auditory event-related potentials (AERPs). A total of 18 healthy volunteer recreational air SCUBA divers participated in the study. AERPs were recorded in pre-dive, deep-dive, and post-dive sessions. False-positive score variables were found with significantly higher differences and longer reaction times of hits during deep-dive and post-dive than pre-dive sessions. Also, P3 amplitudes were significantly reduced and peak latencies were prolonged during both deep-dive and post-dive compared with pre-dive sessions. We observed that nitrogen narcosis at 500 kPa pressure in the dry hyperbaric chamber has a mild-to-moderate negative effect on the cognitive performance of recreational air SCUBA divers, which threatened the safety of diving. Although relatively decreased, this effect also continued in the post-dive sessions. These negative effects are especially important for divers engaged in open-sea diving. Our results show crucial implications for the kinds of control measures that can help to prevent nitrogen narcosis and diving accidents at depths up to 40 msw.

Modulation of early auditory processing by visual information: Prediction or bimodal integration?

What happens if a visual cue misleads auditory expectations? Previous studies revealed an early visuo–auditory incongruency effect, so-called incongruency response (IR) of the auditory event-related brain potential (ERP), occurring 100 ms after onset of the sound being incongruent to the preceding visual cue. So far, this effect has been ascribed to reflect the mismatch between auditory sensory expectation activated by visual predictive information and the actual sensory input. Thus, an IR should be confined to an asynchronous presentation of visual cue and sound. Alternatively, one could argue that frequently presented congruent visual-cue–sound combinations are integrated into a bimodal representation whereby violation of the visual–auditory relationship results in a bimodal feature mismatch (the IR should be obtained with asynchronous and with synchronous presentation). In an asynchronous condition, an either high-pitched or low-pitched sound was preceded by a visual note symbol presented above or below a fixation cross (90% congruent; 10% incongruent), while in a synchronous condition, both were presented simultaneously. High-pitched and low-pitched sounds were presented with different probabilities (83% vs. 17%) to form a strong association between bimodal stimuli. In both conditions, tones with pitch incongruent with the location of the note symbols elicited incongruency effects in the N2 and P3 ERPs; however, the IR was only elicited in the asynchronous condition. This finding supports the sensorial prediction error hypothesis stating that the amplitude of the auditory ERP 100 ms after sound onset is enhanced in response to unexpected compared with expected but otherwise identical sounds.

Modulation of auditory sensory memory by chronic clinical pain and acute experimental pain: a mismatch negativity study

Pain, especially chronic pain, can lead to cognitive deficits. Mismatch negativity (MMN) is a change-specific component of the auditory event-related brain potential (ERP) that is thought to provide a unique window into sensory memory processes. The present study was designed to determine how chronic and acute pain affects auditory sensory memory. In experiment 1, MMNs elicited by standard and deviant auditory stimuli at short and long inter-stimulus intervals (ISIs) were compared between trigeminal neuralgia (TN) patients and demographically matched healthy controls (HCs). The TN patients were found to have stronger attenuation of the MMN at longer ISIs than HCs. Correlation analysis revealed a significant positive correlation between the sensory subscale of McGill Pain Questionnaire and MMN amplitude reduction across ISI conditions. In experiment 2, MMNs recorded before, during, and after the cold pressor test were compared in healthy subjects. MMN amplitude was significantly reduced during pain exposure and recovered immediately thereafter. These results suggest that both chronic pain and acute pain can interfere with automatic change detection processes in the brain. This study provides the first evidence that chronic pain patients have a faster auditory memory trace decay than HCs.

Event-Related Potentials in the Clinical High-Risk (CHR) State for Psychosis: A Systematic Review

There is emerging evidence that identification and treatment of individuals in the prodromal or clinical high-risk (CHR) state for psychosis can reduce the probability that they will develop a psychotic disorder. Event-related brain potentials (ERPs) are a noninvasive neurophysiological technique that holds promise for improving our understanding of neurocognitive processes underlying the CHR state. We aimed to systematically review the current literature on cognitive ERP studies of the CHR population, in order to summarize and synthesize the results, and their implications for our understanding of the CHR state. Across studies, amplitudes of the auditory P300 and duration mismatch negativity (MMN) ERPs appear reliably reduced in CHR individuals, suggesting that underlying impairments in detecting changes in auditory stimuli are a sensitive early marker of the psychotic disease process. There are more limited data indicating that an earlier-latency auditory ERP response, the N100, is also reduced in amplitude, and in the degree to which it is modulated by stimulus characteristics, in the CHR population. There is also evidence that a number of auditory ERP measures (including P300, MMN and N100 amplitudes, and N100 gating in response to repeated stimuli) can further refine our ability to detect which CHR individuals are most at risk for developing psychosis. Thus, further research is warranted to optimize the predictive power of algorithms incorporating these measures, which could help efforts to target psychosis prevention interventions toward those most in need.

Animacy-based predictions in language comprehension are robust: Contextual cues modulate but do not nullify them

Couldn׳t a humble coconut hurt a gardener? At least in the first instance, the brain seems to assume that it should not: we perceive inanimate entities such as coconuts as poor event instigators (“Actors”). Ideally, entities causing a change in another entity should be animate and this assumption not only influences event perception but also carries over to language comprehension. We present three auditory event-related brain potential (ERP) studies on the processing of inanimate and animate subjects and objects in simple transitive sentences in Tamil. ERP responses were measured at the second argument (event participant) in all three studies. Experiment 1 employed all possible animacy combinations of Actors and Undergoers (affected participants) in Actor- and Undergoer-initial verb-final orders. Experiments 2 and 3 employed a fairly novel context design that enabled us to compare ERPs evoked by identical auditory material to differing contextual expectations: Experiment 2 focussed on constructions in which an inanimate Actor acts upon an inanimate Undergoer, whereas Experiment 3 examined whether and how a preceding context modulates the prediction for an ideal Actor. Results showed an N400 effect when the prediction for an ideal (animate) Actor following an Undergoer was not met, thus further supporting the cross-linguistically robust nature of animacy preferences. In addition, though specific contextual cues that are indicative of a forthcoming non-ideal Actor may reduce this negativity in comparison to when such cues are not available, they nevertheless do not nullify it, suggesting that animacy-based predictions are stronger than contextual cues in online language comprehension.

Analyzing the auditory scene: neurophysiologic evidence of a dissociation between detection of regularity and detection of change.

Detecting regularity and change in the environment is crucial for survival, as it enables making predictions about the world and informing goal-directed behavior. In the auditory modality, the detection of regularity involves segregating incoming sounds into distinct perceptual objects (stream segregation). The detection of change from this within-stream regularity is associated with the mismatch negativity, a component of auditory event-related brain potentials (ERPs). A central unanswered question is how the detection of regularity and the detection of change are interrelated, and whether attention affects the former, the latter, or both. Here we show that the detection of regularity and the detection of change can be empirically dissociated, and that attention modulates the detection of change without precluding the detection of regularity, and the perceptual organization of the auditory background into distinct streams. By applying frequency spectra analysis on the EEG of subjects engaged in a selective listening task, we found distinct peaks of ERP synchronization, corresponding to the rhythm of the frequency streams, independently of whether the stream was attended or ignored. Our results provide direct neurophysiological evidence of regularity detection in the auditory background, and show that it can occur independently of change detection and in the absence of attention.

Cross-linguistic variation in the neurophysiological response to semantic processing: Evidence from anomalies at the borderline of awareness

The N400 event-related brain potential (ERP) has played a major role in the examination of how the human brain processes meaning. For current theories of the N400, classes of semantic inconsistencies which do not elicit N400 effects have proven particularly influential. Semantic anomalies that are difficult to detect are a case in point (“borderline anomalies”, e.g. “After an air crash, where should the survivors be buried?”), engendering a late positive ERP response but no N400 effect in English (Sanford, Leuthold, Bohan, & Sanford, 2011). In three auditory ERP experiments, we demonstrate that this result is subject to cross-linguistic variation. In a German version of Sanford and colleagues′ experiment (Experiment 1), detected borderline anomalies elicited both N400 and late positivity effects compared to control stimuli or to missed borderline anomalies. Classic easy-to-detect semantic (non-borderline) anomalies showed the same pattern as in English (N400 plus late positivity). The cross-linguistic difference in the response to borderline anomalies was replicated in two additional studies with a slightly modified task (Experiment 2a: German; Experiment 2b: English), with a reliable LANGUAGE×ANOMALY interaction for the borderline anomalies confirming that the N400 effect is subject to systematic cross-linguistic variation. We argue that this variation results from differences in the language-specific default weighting of top-down and bottom-up information, concluding that N400 amplitude reflects the interaction between the two information sources in the form-to-meaning mapping.

Effects of Nicotine on the Neurophysiological and Behavioral Effects of Ketamine in Humans

Background: N-methyl-d-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia and its associated neurocognitive impairments. The high rate of cigarette smoking in schizophrenia raises questions about how nicotine modulates putative NMDA receptor hypofunction in the illness. Accordingly, we examined the modulatory effects of brain nicotinic acetylcholine receptor (nAChR) stimulation on NMDA receptor hypofunction by examining the interactive effects of nicotine, a nAChR agonist, and ketamine, a non-competitive NMDA receptor antagonist, on behavioral and neurophysiological measures in healthy human volunteers.Methods: From an initial sample of 17 subjects (age range 18–55 years), 8 subjects successfully completed 4 test sessions, each separated by at least 3 days, during which they received ketamine or placebo and two injections of nicotine or placebo in a double-blind, counterbalanced manner. Schizophrenia-like effects Positive and Negative Syndrome Scale, perceptual alterations Clinician Administered Dissociative Symptoms Scale, subjective effects Visual Analog Scale and auditory event-related brain potentials (mismatch negativity, MMN; P300) were assessed during each test session.Results: Consistent with existing studies, ketamine induced transient schizophrenia-like behavioral effects. P300 was reduced and delayed by ketamine regardless of whether it was elicited by a target (P3b) or novel (P3a) stimulus, while nicotine only reduced the amplitude of P3a. Nicotine did not rescue P300 from the effects of ketamine; the interactions of ketamine and nicotine were not significant. While nicotine significantly reduced MMN amplitude, ketamine did not.Conclusion: Nicotine failed to modulate ketamine-induced neurophysiological and behavioral effects in this preliminary study. Interestingly, ketamine reduced P3b amplitude and nicotine reduced P3a amplitude, suggesting independent roles of NMDA receptor and nAChR in the generation of P3b and P3a, respectively.

Auditory event-related brain potentials for an early discrimination between normal and pathological brain aging.

The brain as a system with gradually decreasing resources maximizes its chances by reorganizing neural networks to ensure efficient performance. Auditory event-related potentials were recorded in 28 healthy volunteers comprising 14 young and 14 elderly subjects in auditory discrimination motor task (low frequency tone – right hand movement and high frequency tone – left hand movement). The amplitudes of the sensory event-related potential components (N1, P2) were more pronounced with increasing age for either tone and this effect for P2 amplitude was more pronounced in the frontal region. The latency relationship of N1 between the groups was tone-dependent, while that of P2 was tone-independent with a prominent delay in the elderly group over all brain regions. The amplitudes of the cognitive components (N2, P3) diminished with increasing age and the hemispheric asymmetry of N2 (but not for P3) reduced with increasing age. Prolonged N2 latency with increasing age was widespread for either tone while between-group difference in P3 latency was tone-dependent. High frequency tone stimulation and movement requirements lead to P3 delay in the elderly group. The amplitude difference of the sensory components between the age groups could be due to a general greater alertness, less expressed habituation, or decline in the ability to retreat attentional resources from the stimuli in the elderly group. With aging, a neural circuit reorganization of the brain activity affects the cognitive processes. The approach used in this study is useful for an early discrimination between normal and pathological brain aging for early treatment of cognitive alterations and dementia.

The N1-suppression effect for self-initiated sounds is independent of attention.

BackgroundIf we initiate a sound by our own motor behavior, the N1 component of the auditory event-related brain potential (ERP) that the sound elicits is attenuated compared to the N1 elicited by the same sound when it is initiated externally. It has been suggested that this N1 suppression results from an internal predictive mechanism that is in the service of discriminating the sensory consequences of one’s own actions from other sensory input. As the N1-suppression effect is becoming a popular approach to investigate predictive processing in cognitive and social neuroscience, it is important to exclude an alternative interpretation not related to prediction. According to the attentional account, the N1 suppression is due to a difference in the allocation of attention between self- and externally-initiated sounds. To test this hypothesis, we manipulated the allocation of attention to the sounds in different blocks: Attention was directed either to the sounds, to the own motor acts or to visual stimuli. If attention causes the N1-suppression effect, then manipulating attention should affect the effect for self-initiated sounds.ResultsWe found N1 suppression in all conditions. The N1 per se was affected by attention, but there was no interaction between attention and self-initiation effects. This implies that self-initiation N1 effects are not caused by attention.ConclusionsThe present results support the assumption that the N1-suppression effect for self-initiated sounds indicates the operation of an internal predictive mechanism. Furthermore, while attention had an influence on the N1a, N1b, and N1c components, the N1-suppression effect was confined to the N1b and N1c subcomponents suggesting that the major contribution to the auditory N1-suppression effect is circumscribed to late N1 components.

Neural dynamics of audiovisual synchrony and asynchrony perception in 6-month-old infants.

Young infants are sensitive to multisensory temporal synchrony relations, but the neural dynamics of temporal interactions between vision and audition in infancy are not well understood. We investigated audiovisual synchrony and asynchrony perception in 6-month-old infants using event-related brain potentials (ERP). In a prior behavioral experiment (n = 45), infants were habituated to an audiovisual synchronous stimulus and tested for recovery of interest by presenting an asynchronous test stimulus in which the visual stream was delayed with respect to the auditory stream by 400 ms. Infants who behaviorally discriminated the change in temporal alignment were included in further analyses. In the EEG experiment (final sample: n = 15), synchronous and asynchronous stimuli (visual delay of 400 ms) were presented in random order. Results show latency shifts in the auditory ERP components N1 and P2 as well as the infant ERP component Nc. Latencies in the asynchronous condition were significantly longer than in the synchronous condition. After video onset but preceding the auditory onset, amplitude modulations propagating from posterior to anterior sites and related to the Pb component of infants’ ERP were observed. Results suggest temporal interactions between the two modalities. Specifically, they point to the significance of anticipatory visual motion for auditory processing, and indicate young infants’ predictive capacities for audiovisual temporal synchrony relations.

Deficit in the preattentive processing of syllabic duration and VOT in children with dyslexia

The aim of this experiment was to examine the preattentive processing of syllables in 9–11-year-old children with dyslexia and matched controls using the Mismatch Negativity (MMN), an auditory Event-Related brain potential (ERP) related to preattentive discrimination. Children were presented with a sequence of syllables that included standards (the syllable “Ba”) and deviants in vowel frequency, vowel duration and Voice Onset Time (VOT) that were either close to or far from the standard (Small and Large deviants). No between-group differences were found for frequency deviants. However, whilst normal-reading children showed larger MMNs to Large than to Small deviants in vowel duration and VOT, no such deviance size effect was found in children with dyslexia. These results are taken to indicate that the preattentive processing of vowel duration and VOT is impaired in children with dyslexia, with no impairment in the processing of vowel frequency deviants. By revealing processing deficits of both duration and VOT deviants, these results suggest a strong link between acoustical and phonological processing.

P-1260 - Neurochemical modulation of auditory processing in healthy controls stratified for low and high auditory hallucinatory experiences

Contributing to poor global functioning, auditory hallucinations (AH) also interfere with elementary cognitive processes, including auditory discrimination. This is evidenced in schizophrenic (SZ) hallucinators (vs. non-hallucinators) by a greater reduction of the MMN, an auditory event-related brain potential (ERP) generated in part by NMDA receptor activity and normalized with nicotinic (nACh) agonist treatment. To increase our understanding of NMDA-nACh interactions with auditory processing, using healthy young adults varying in their degree of experience with AH, thereby reducing the confounding influence of illness chronicity and medication associated with the study of SZ patients. To investigate MMN differences between low and high AH subjects during separate and combined administration of ketamine, an NMDA antagonist, and nicotine, an nACh agonist. In 40 healthy controls, all rated for AH with the Bell Object Relations and Reality Testing Inventory, MMN to frequency deviants was assessed in a randomized, placebo-controlled crossover design involving the separate and combined administration of a intravenous sub-psychotomimetic dose of ketamine (0.04 mg/kg) and a dose of nicotine gum (4 mg). In high AH subjects, ketamine reduced MMN, with the resulting amplitude being smaller than that of low AH subjects. This ketamine-induced MMN reduction was evident only with placebo gum; furthermore combined nicotine-ketamine treatment acted to increase MMN in high scorers. AH in otherwise healthy individuals is associated with heightened sensitivity to NMDA receptor blockade, the effects of which are moderated by nicotinic neurotransmission. Both neurotransmitters may interact to moderate auditory processing and AH in SZ.

Nicotine, Auditory Sensory Memory, and sustained Attention in a Human Ketamine Model of Schizophrenia: Moderating Influence of a Hallucinatory Trait

Background: The procognitive actions of the nicotinic acetylcholine receptor (nAChR) agonist nicotine are believed, in part, to motivate the excessive cigarette smoking in schizophrenia, a disorder associated with deficits in multiple cognitive domains, including low-level auditory sensory processes and higher-order attention-dependent operations. Objectives: As N-methyl-d-aspartate receptor (NMDAR) hypofunction has been shown to contribute to these cognitive impairments, the primary aims of this healthy volunteer study were to: (a) to shed light on the separate and interactive roles of nAChR and NMDAR systems in the modulation of auditory sensory memory (and sustained attention), as indexed by the auditory event-related brain potential – mismatch negativity (MMN), and (b) to examine how these effects are moderated by a predisposition to auditory hallucinations/delusions (HD). Methods: In a randomized, double-blind, placebo-controlled design involving a low intravenous dose of ketamine (0.04 mg/kg) and a 4 mg dose of nicotine gum, MMN, and performance on a rapid visual information processing (RVIP) task of sustained attention were examined in 24 healthy controls psychometrically stratified as being lower (L-HD, n = 12) or higher (H-HD) for HD propensity. Results: Ketamine significantly slowed MMN, and reduced MMN in H-HD, with amplitude attenuation being blocked by the co-administration of nicotine. Nicotine significantly enhanced response speed [reaction time (RT)] and accuracy (increased % hits and d′ and reduced false alarms) on the RVIP, with improved performance accuracy being prevented when nicotine was administered with ketamine. Both % hits and d′, as well as RT were poorer in H-HD (vs. L-HD) and while hit rate and d′ was increased by nicotine in H-HD, RT was slowed by ketamine in L-HD. Conclusions: Nicotine alleviated ketamine-induced sensory memory impairment and improved attention, particularly in individuals prone to HD.

Could audiovisual training be used to improve cognition in extremely low birth weight children?

To study whether a dyslexia remediation programme, Audilex, improves cognition in extremely low birth (ELBW) children. Six-year-old ELBW children were allocated to a 5-week training with Audilex or playing control computer games. Before and after intervention, auditory event-related brain potentials (ERP) to sound changes were recorded and reading related skills assessed. Primary outcome was the mismatch negativity (MMN) component of ERP. Secondary outcomes were Audilex Test (ability to perform the Audilex games), the reading skills after the intervention and 2 years later. Of eligible children, 39 (54%) consented and 22 (30%) completed the protocol. The MMN responses to the frequency (p = 0.02) and duration deviants (p < 0.01) increased after Audilex training (n = 11), but not after control game playing (n = 11). Audilex Test performance was similar in both groups. The reading skills were similar after intervention and 2 years later; word reading score 59.7, 66.8 and 74.9 and comprehensive reading score 8.1, 8.8 and 9.4 in Audilex, Control and healthy class-mate children, respectively. Although all children did not complete the protocol, the results suggest that training with Audilex dyslexia programme might be beneficial for enhancing neural-level sound discrimation and possibly reading skills in ELBW children. A larger trial is warranted.