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.

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 subsequenttargets. 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 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.

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.

AbstractAttentional control outside of the laboratory operates in multisensory settings, but the development of mechanisms subserving such control remains poorly understood. We investigated when, over the course of childhood, adult-like attentional control mechanisms begin to emerge. Children aged five, seven, and nine were compared with adults on behavioural performance in a computer game-like multisensory spatial cueing task, while simultaneous 129-channel EEG was recorded. Markers of attentional control were behavioural spatial cueing effects and the N2pc ERP component (analysed both traditionally and using a novel, multivariate electrical neuroimaging framework). In behaviour, adult-like visual attentional control was present from age 7 onwards, whereas multisensory control was not seen in children. In EEG, multivariate analyses of the activity over the N2pc time-window, revealed stable patterns of brain activity in children. Adult activity patterns linked to visual attentional control were present age 7 onwards, mirroring behaviour. Activity patterns linked to multisensory control were found in 9-year-olds, even though such patterns were not noted in behaviour. By combining rigorous yet naturalistic paradigms with multivariate signal analyses, we provided new insights into the development of visual attentional control skills vis-à-vis multisensory attentional control, thus generating a more complete account of attentional development.HighlightsBehaviourally, visual attentional control, as measured by task-set contingent attentional capture, was found to reach an adult-like state as early as age 7Behaviourally, attentional enhancement from multisensory stimuli was not found in 9-year-olds, but their EEG topographic patterns were different for multisensory vs. purely visual distractorsTraditional visual attentional event-related analyses, such as the N2pc, are not sensitive to detect attentional enhancement for multisensory objects in adults, and visual or multisensory attention in childrenSensitive, multivariate analyses of the event-related potential signal, such as electrical neuroimaging, are adept at revealing the neural underpinnings of attentional control processes over development