Longstanding Auditory Sensory and Semantic Differences in Preterm Born Children.

More than 10% of births are preterm, and the long-term consequences on sensory and semantic processing of non-linguistic information remain poorly understood. 17 very preterm-born children (born at < 33 weeks gestational age) and 15 full-term controls were tested at 10 years old with an auditory object recognition task, while 64-channel auditory evoked potentials (AEPs) were recorded. Sounds consisted of living (animal and human vocalizations) and manmade objects (e.g. household objects, instruments, and tools). Despite similar recognition behavior, AEPs strikingly differed between full-term and preterm children. Starting at 50ms post-stimulus onset, AEPs from preterm children differed topographically from their full-term counterparts. Over the 108-224ms post-stimulus period, full-term children showed stronger AEPs in response to living objects, whereas preterm born children showed the reverse pattern; i.e. stronger AEPs in response to manmade objects. Differential brain activity between semantic categories could reliably classify children according to their preterm status. Moreover, this opposing pattern of differential responses to semantic categories of sounds was also observed in source estimations within a network of occipital, temporal and frontal regions. This study highlights how early life experience in terms of preterm birth shapes sensory and object processing later on in life.

Brain responses to food viewing in women during pregnancy and post partum and their relationship with metabolic health: study protocol for the FOODY Brain Study, a prospective observational study.

INTRODUCTION: Food cravings are common in pregnancy and along with emotional eating and eating in the absence of hunger, they are associated with excessive weight gain and adverse effects on metabolic health including gestational diabetes mellitus (GDM). Women with GDM also show poorer mental health, which further can contribute to dysregulated eating behaviour. Food cravings can lead to greater activity in brain centres known to be involved in food 'wanting' and reward valuation as well as emotional eating. They are also related to gestational weight gain. Thus, there is a great need to link implicit brain responses to food with explicit measures of food intake behaviour, especially in the perinatal period. The aim of this study is to investigate the spatiotemporal brain dynamics to visual presentations of food in women during pregnancy and in the post partum, and link these brain responses to the eating behaviour and metabolic health outcomes in women with and without GDM. METHODS AND ANALYSIS: This prospective observational study will include 20 women with and 20 without GDM, that have valid data for the primary outcomes. Data will be assessed at 24-36 weeks gestational age and at 6 months post partum. The primary outcomes are brain responses to food pictures of varying carbohydrate and fat content during pregnancy and in the post partum using electroencephalography. Secondary outcomes including depressive symptoms, current mood and eating behaviours will be assessed with questionnaires, objective eating behaviours will be measured using Auracle and stress will be measured with heart rate and heart rate variability (Actiheart). Other secondary outcome measures include body composition and glycaemic control parameters. ETHICS AND DISSEMINATION: The Human Research Ethics Committee of the Canton de Vaud approved the study protocol (2021-01976). Study results will be presented at public and scientific conferences and in peer-reviewed journals.

Plasticity Changes in Central Auditory Systems of School-Age Children Following a Brief Training With a Remote Microphone System.

OBJECTIVES: The objective of this study was to investigate whether a brief speech-in-noise training with a remote microphone (RM) system (favorable listening condition) would contribute to enhanced post-training plasticity changes in the auditory system of school-age children. DESIGN: Before training, event-related potentials (ERPs) were recorded from 49 typically developing children, who actively identified two syllables in quiet and in noise (+5 dB signal-to-noise ratio [SNR]). During training, children completed the same syllable identification task as in the pre-training noise condition, but received feedback on their performance. Following random assignment, half of the sample used an RM system during training (experimental group), while the other half did not (control group). That is, during training' children in the experimental group listened to a more favorable speech signal (+15 dB SNR) than children from the control group (+5 dB SNR). ERPs were collected after training at +5 dB SNR to evaluate the effects of training with and without the RM system. Electrical neuroimaging analyses quantified the effects of training in each group on ERP global field power (GFP) and topography, indexing response strength and network changes, respectively. Behavioral speech-perception-in-noise skills of children were also evaluated and compared before and after training. We hypothesized that training with the RM system (experimental group) would lead to greater enhancement of GFP and greater topographical changes post-training than training without the RM system (control group). We also expected greater behavioral improvement on the speech-perception-in-noise task when training with than without the RM system. RESULTS: GFP was enhanced after training only in the experimental group. These effects were observed on early time-windows corresponding to traditional P1-N1 (100 to 200 msec) and P2-N2 (200 to 400 msec) ERP components. No training effects were observed on response topography. Finally, both groups increased their speech-perception-in-noise skills post-training. CONCLUSIONS: Enhanced GFP after training with the RM system indicates plasticity changes in the neural representation of sound resulting from listening to an enriched auditory signal. Further investigation of longer training or auditory experiences with favorable listening conditions is needed to determine if that results in long-term speech-perception-in-noise benefits.

Mitochondrial, exosomal miR137-COX6A2 and gamma synchrony as biomarkers of parvalbumin interneurons, psychopathology, and neurocognition in schizophrenia.

Early detection and intervention in schizophrenia requires mechanism-based biomarkers that capture neural circuitry dysfunction, allowing better patient stratification, monitoring of disease progression and treatment. In prefrontal cortex and blood of redox dysregulated mice (Gclm-KO ± GBR), oxidative stress induces miR-137 upregulation, leading to decreased COX6A2 and mitophagy markers (NIX, Fundc1, and LC3B) and to accumulation of damaged mitochondria, further exacerbating oxidative stress and parvalbumin interneurons (PVI) impairment. MitoQ, a mitochondria-targeted antioxidant, rescued all these processes. Translating to early psychosis patients (EPP), blood exosomal miR-137 increases and COX6A2 decreases, combined with mitophagy markers alterations, suggest that observations made centrally and peripherally in animal model were reflected in patients' blood. Higher exosomal miR-137 and lower COX6A2 levels were associated with a reduction of ASSR gamma oscillations in EEG. As ASSR requires proper PVI-related networks, alterations in miR-137/COX6A2 plasma exosome levels may represent a proxy marker of PVI cortical microcircuit impairment. EPP can be stratified in two subgroups: (a) a patients' group with mitochondrial dysfunction "Psy-D", having high miR-137 and low COX6A2 levels in exosomes, and (b) a "Psy-ND" subgroup with no/low mitochondrial impairment, including patients having miR-137 and COX6A2 levels in the range of controls. Psy-D patients exhibited more impaired ASSR responses in association with worse psychopathological status, neurocognitive performance, and global and social functioning, suggesting that impairment of PVI mitochondria leads to more severe disease profiles. This stratification would allow, with high selectivity and specificity, the selection of patients for treatments targeting brain mitochondria dysregulation and capture the clinical and functional efficacy of future clinical trials.

Towards understanding how we pay attention in naturalistic visual search settings.

Research on attentional control has largely focused on single senses and the importance of behavioural goals in controlling attention. However, everyday situations are multisensory and contain regularities, both likely influencing attention. We investigated how visual attentional capture is simultaneously impacted by top-down goals, the multisensory nature of stimuli, and the contextual factors of stimuli's semantic relationship and temporal predictability. Participants performed a multisensory version of the Folk et al. (1992) spatial cueing paradigm, searching for a target of a predefined colour (e.g. a red bar) within an array preceded by a distractor. We manipulated: 1) stimuli's goal-relevance via distractor's colour (matching vs. mismatching the target), 2) stimuli's multisensory nature (colour distractors appearing alone vs. with tones), 3) the relationship between the distractor sound and colour (arbitrary vs. semantically congruent) and 4) the temporal predictability of distractor onset. Reaction-time spatial cueing served as a behavioural measure of attentional selection. We also recorded 129-channel event-related potentials (ERPs), analysing the distractor-elicited N2pc component both canonically and using a multivariate electrical neuroimaging framework. Behaviourally, arbitrary target-matching distractors captured attention more strongly than semantically congruent ones, with no evidence for context modulating multisensory enhancements of capture. Notably, electrical neuroimaging of surface-level EEG analyses revealed context-based influences on attention to both visual and multisensory distractors, in how strongly they activated the brain and type of activated brain networks. For both processes, the context-driven brain response modulations occurred long before the N2pc time-window, with topographic (network-based) modulations at ∼30 ms, followed by strength-based modulations at ∼100 ms post-distractor onset. Our results reveal that both stimulus meaning and predictability modulate attentional selection, and they interact while doing so. Meaning, in addition to temporal predictability, is thus a second source of contextual information facilitating goal-directed behaviour. More broadly, in everyday situations, attention is controlled by an interplay between one's goals, stimuli's perceptual salience, meaning and predictability. Our study calls for a revision of attentional control theories to account for the role of contextual and multisensory control.

The development of attentional control mechanisms in multisensory environments.

Outside the laboratory, people need to pay attention to relevant objects that are typically multisensory, but it remains poorly understood how the underlying neurocognitive mechanisms develop. We investigated when adult-like mechanisms controlling one's attentional selection of visual and multisensory objects emerge across childhood. Five-, 7-, and 9-year-olds were compared with adults in their performance on a computer game-like multisensory spatial cueing task, while 129-channel EEG was simultaneously recorded. Markers of attentional control were behavioural spatial cueing effects and the N2pc ERP component (analysed traditionally and using a multivariate electrical neuroimaging framework). In behaviour, adult-like visual attentional control was present from age 7 onwards, whereas multisensory control was absent in all children groups. In EEG, multivariate analyses of the activity over the N2pc time-window revealed stable brain activity patterns in children. Adult-like visual-attentional control EEG patterns were present age 7 onwards, while multisensory control activity patterns were found in 9-year-olds (albeit behavioural measures showed no effects). By combining rigorous yet naturalistic paradigms with multivariate signal analyses, we demonstrated that visual attentional control seems to reach an adult-like state at ∼7 years, before adult-like multisensory control, emerging at ∼9 years. These results enrich our understanding of how attention in naturalistic settings develops.

Selective attention to sound features mediates cross-modal activation of visual cortices.

Contemporary schemas of brain organization now include multisensory processes both in low-level cortices as well as at early stages of stimulus processing. Evidence has also accumulated showing that unisensory stimulus processing can result in cross-modal effects. For example, task-irrelevant and lateralised sounds can activate visual cortices; a phenomenon referred to as the auditory-evoked contralateral occipital positivity (ACOP). Some claim this is an example of automatic attentional capture in visual cortices. Other results, however, indicate that context may play a determinant role. Here, we investigated whether selective attention to spatial features of sounds is a determining factor in eliciting the ACOP. We recorded high-density auditory evoked potentials (AEPs) while participants selectively attended and discriminated sounds according to four possible stimulus attributes: location, pitch, speaker identity or syllable. Sound acoustics were held constant, and their location was always equiprobable (50% left, 50% right). The only manipulation was to which sound dimension participants attended. We analysed the AEP data from healthy participants within an electrical neuroimaging framework. The presence of sound-elicited activations of visual cortices depended on the to-be-discriminated, goal-based dimension. The ACOP was elicited only when participants were required to discriminate sound location, but not when they attended to any of the non-spatial features. These results provide a further indication that the ACOP is not automatic. Moreover, our findings showcase the interplay between task-relevance and spatial (un)predictability in determining the presence of the cross-modal activation of visual cortices.

Brain and Cognitive Mechanisms of Top-Down Attentional Control in a Multisensory World: Benefits of Electrical Neuroimaging.

In real-world environments, information is typically multisensory, and objects are a primary unit of information processing. Object recognition and action necessitate attentional selection of task-relevant from among task-irrelevant objects. However, the brain and cognitive mechanisms governing these processes remain not well understood. Here, we demonstrate that attentional selection of visual objects is controlled by integrated top-down audiovisual object representations ("attentional templates") while revealing a new brain mechanism through which they can operate. In multistimulus (visual) arrays, attentional selection of objects in humans and animal models is traditionally quantified via "the N2pc component": spatially selective enhancements of neural processing of objects within ventral visual cortices at approximately 150-300 msec poststimulus. In our adaptation of Folk et al.'s [Folk, C. L., Remington, R. W., & Johnston, J. C. Involuntary covert orienting is contingent on attentional control settings. Journal of Experimental Psychology: Human Perception and Performance, 18, 1030-1044, 1992] spatial cueing paradigm, visual cues elicited weaker behavioral attention capture and an attenuated N2pc during audiovisual versus visual search. To provide direct evidence for the brain, and so, cognitive, mechanisms underlying top-down control in multisensory search, we analyzed global features of the electrical field at the scalp across our N2pcs. In the N2pc time window (170-270 msec), color cues elicited brain responses differing in strength and their topography. This latter finding is indicative of changes in active brain sources. Thus, in multisensory environments, attentional selection is controlled via integrated top-down object representations, and so not only by separate sensory-specific top-down feature templates (as suggested by traditional N2pc analyses). We discuss how the electrical neuroimaging approach can aid research on top-down attentional control in naturalistic, multisensory settings and on other neurocognitive functions in the growing area of real-world neuroscience.

Sounds enhance visual completion processes.

Everyday vision includes the detection of stimuli, figure-ground segregation, as well as object localization and recognition. Such processes must often surmount impoverished or noisy conditions; borders are perceived despite occlusion or absent contrast gradients. These illusory contours (ICs) are an example of so-called mid-level vision, with an event-related potential (ERP) correlate at ∼100-150 ms post-stimulus onset and originating within lateral-occipital cortices (the ICeffect). Presently, visual completion processes supporting IC perception are considered exclusively visual; any influence from other sensory modalities is currently unknown. It is now well-established that multisensory processes can influence both low-level vision (e.g. detection) as well as higher-level object recognition. By contrast, it is unknown if mid-level vision exhibits multisensory benefits and, if so, through what mechanisms. We hypothesized that sounds would impact the ICeffect. We recorded 128-channel ERPs from 17 healthy, sighted participants who viewed ICs or no-contour (NC) counterparts either in the presence or absence of task-irrelevant sounds. The ICeffect was enhanced by sounds and resulted in the recruitment of a distinct configuration of active brain areas over the 70-170 ms post-stimulus period. IC-related source-level activity within the lateral occipital cortex (LOC), inferior parietal lobe (IPL), as well as primary visual cortex (V1) were enhanced by sounds. Moreover, the activity in these regions was correlated when sounds were present, but not when absent. Results from a control experiment, which employed amodal variants of the stimuli, suggested that sounds impact the perceived brightness of the IC rather than shape formation per se. We provide the first demonstration that multisensory processes augment mid-level vision and everyday visual completion processes, and that one of the mechanisms is brightness enhancement. These results have important implications for the design of treatments and/or visual aids for low-vision patients.

What's what in auditory cortices?

Distinct anatomical and functional pathways are postulated for analysing a sound's object-related ('what') and space-related ('where') information. It remains unresolved to which extent distinct or overlapping neural resources subserve specific object-related dimensions (i.e. who is speaking and what is being said can both be derived from the same acoustic input). To address this issue, we recorded high-density auditory evoked potentials (AEPs) while participants selectively attended and discriminated sounds according to their pitch, speaker identity, uttered syllable ('what' dimensions) or their location ('where'). Sound acoustics were held constant across blocks; the only manipulation involved the sound dimension that participants had to attend to. The task-relevant dimension was varied across blocks. AEPs from healthy participants were analysed within an electrical neuroimaging framework to differentiate modulations in response strength from modulations in response topography; the latter of which forcibly follow from changes in the configuration of underlying sources. There were no behavioural differences in discrimination of sounds across the 4 feature dimensions. As early as 90ms post-stimulus onset, AEP topographies differed across 'what' conditions, supporting a functional sub-segregation within the auditory 'what' pathway. This study characterises the spatio-temporal dynamics of segregated, yet parallel, processing of multiple sound object-related feature dimensions when selective attention is directed to them.

Treatment in early psychosis with N-acetyl-cysteine for 6months improves low-level auditory processing: Pilot study.

Sensory impairments constitute core dysfunctions in schizophrenia. In the auditory modality, impaired mismatch negativity (MMN) has been observed in chronic schizophrenia and may reflect N-methyl-d-aspartate (NMDA) hypo-function, consistent with models of schizophrenia based on oxidative stress. Moreover, a recent study demonstrated deficits in the N100 component of the auditory evoked potential (AEP) in early psychosis patients. Previous work has shown that add-on administration of the glutathione precursor N-acetyl-cysteine (NAC) improves the MMN and clinical symptoms in chronic schizophrenia. To date, it remains unknown whether NAC also improves general low-level auditory processing and if its efficacy would extend to early-phase psychosis. We addressed these issues with a randomized, double-blind study of a small sample (N=15) of early psychosis (EP) patients and 18 healthy controls from whom AEPs were recorded during an active, auditory oddball task. Patients were recorded twice: once prior to NAC/placebo administration and once after six months of treatment. The N100 component was significantly smaller in patients before NAC administration versus controls. Critically, NAC administration improved this AEP deficit. Source estimations revealed increased activity in the left temporo-parietal lobe in patients after NAC administration. Overall, the data from this pilot study, which call for replication in a larger sample, indicate that NAC improves low-level auditory processing in early psychosis.

The coupling of low-level auditory dysfunction and oxidative stress in psychosis patients.

Patients diagnosed with schizophrenia often present with low-level sensory deficits. It is an open question whether there is a functional link between these deficits and the pathophysiology of the disease, e.g. oxidative stress and glutathione (GSH) metabolism dysregulation. Auditory evoked potentials (AEPs) were recorded from 21 psychosis disorder patients and 30 healthy controls performing an active, auditory oddball task. AEPs to standard sounds were analyzed within an electrical neuroimaging framework. A peripheral measure of participants' redox balance, the ratio of glutathione peroxidase and glutathione reductase activities (GPx/GR), was correlated with the AEP data. Patients displayed significantly decreased AEPs over the time window of the P50/N100 complex resulting from significantly weaker responses in the left temporo-parietal lobe. The GPx/GR ratio significantly correlated with patients' brain activity during the time window of the P50/N100 in the medial frontal lobe. We show for the first time a direct coupling between electrophysiological indices of AEPs and peripheral redox dysregulation in psychosis patients. This coupling is limited to stages of auditory processing that are impaired relative to healthy controls and suggests a link between biochemical and sensory dysfunction. The data highlight the potential of low-level sensory processing as a trait-marker of psychosis.

Temporal judgments in multi-sensory space.

To successfully interact with the environment requires a combination of stimulus recognition as well as localization in both space and time, with information moreover coming from multiple senses. Several studies have shown that auditory stimuli last subjectively longer than visual ones of equal duration. Recently, it has also been suggested that stimulus position affects duration perception. The present study investigated how lateral spatial presentation influences sub-second visual and auditory duration judgments. Five experiments were conducted using the duration discrimination paradigm, wherein two stimuli are presented sequentially and participants are asked to judge whether the second stimulus (comparison) is shorter or longer in duration than the first (standard). The number of stimulus positions and the way in which different modality trials were presented (mixed or blocked) varied. Additionally, comparisons were made either within or across modalities. No stable effect of location itself was found. However, in mixed modality experiments there was a clear over-estimation of duration in visual trials when the location of the comparison was different from the standard. This effect was reversed in the same location trials. Auditory judgments were unaffected by location manipulations. Based on these results, we propose the existence of an error-mechanism, according to which a specific duration is added in order to compensate for the loss of duration perception caused by spatial attention shifts between different locations. This mechanism is revealed in spatial and modality-mixed circumstances wherein its over-activation results in a systematic temporal bias.

The context-contingent nature of cross-modal activations of the visual cortex.

Real-world environments are nearly always multisensory in nature. Processing in such situations confers perceptual advantages, but its automaticity remains poorly understood. Automaticity has been invoked to explain the activation of visual cortices by laterally-presented sounds. This has been observed even when the sounds were task-irrelevant and spatially uninformative about subsequent targets. An auditory-evoked contralateral occipital positivity (ACOP) at ~250ms post-sound onset has been postulated as the event-related potential (ERP) correlate of this cross-modal effect. However, the spatial dimension of the stimuli was nevertheless relevant in virtually all prior studies where the ACOP was observed. By manipulating the implicit predictability of the location of lateralised sounds in a passive auditory paradigm, we tested the automaticity of cross-modal activations of visual cortices. 128-channel ERP data from healthy participants were analysed within an electrical neuroimaging framework. The timing, topography, and localisation resembled previous characterisations of the ACOP. However, the cross-modal activations of visual cortices by sounds were critically dependent on whether the sound location was (un)predictable. Our results are the first direct evidence that this particular cross-modal process is not (fully) automatic; instead, it is context-contingent. More generally, the present findings provide novel insights into the importance of context-related factors in controlling information processing across the senses, and call for a revision of current models of automaticity in cognitive sciences.