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.

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.

fMRIflows: A Consortium of Fully Automatic Univariate and Multivariate fMRI Processing Pipelines.

How functional magnetic resonance imaging (fMRI) data are analyzed depends on the researcher and the toolbox used. It is not uncommon that the processing pipeline is rewritten for each new dataset. Consequently, code transparency, quality control and objective analysis pipelines are important for improving reproducibility in neuroimaging studies. Toolboxes, such as Nipype and fMRIPrep, have documented the need for and interest in automated pre-processing analysis pipelines. Recent developments in data-driven models combined with high resolution neuroimaging dataset have strengthened the need not only for a standardized preprocessing workflow, but also for a reliable and comparable statistical pipeline. Here, we introduce fMRIflows: a consortium of fully automatic neuroimaging pipelines for fMRI analysis, which performs standard preprocessing, as well as 1st- and 2nd-level univariate and multivariate analyses. In addition to the standardized pre-processing pipelines, fMRIflows provides flexible temporal and spatial filtering to account for datasets with increasingly high temporal resolution and to help appropriately prepare data for advanced machine learning analyses, improving signal decoding accuracy and reliability. This paper first describes fMRIflows' structure and functionality, then explains its infrastructure and access, and lastly validates the toolbox by comparing it to other neuroimaging processing pipelines such as fMRIPrep, FSL and SPM. This validation was performed on three datasets with varying temporal sampling and acquisition parameters to prove its flexibility and robustness. fMRIflows is a fully automatic fMRI processing pipeline which uniquely offers univariate and multivariate single-subject and group analyses as well as pre-processing.

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.

Chronotopic maps in human supplementary motor area.

Time is a fundamental dimension of everyday experiences. We can unmistakably sense its passage and adjust our behavior accordingly. Despite its ubiquity, the neuronal mechanisms underlying the capacity to perceive time remains unclear. Here, in two experiments using ultrahigh-field 7-Tesla (7T) functional magnetic resonance imaging (fMRI), we show that in the medial premotor cortex (supplementary motor area [SMA]) of the human brain, neural units tuned to different durations are orderly mapped in contiguous portions of the cortical surface so as to form chronomaps. The response of each portion in a chronomap is enhanced by neighboring durations and suppressed by nonpreferred durations represented in distant portions of the map. These findings suggest duration-sensitive tuning as a possible neural mechanism underlying the recognition of time and demonstrate, for the first time, that the representation of an abstract feature such as time can be instantiated by a topographical arrangement of duration-sensitive neural populations.

Topological Features of Electroencephalography are Robust to Re-referencing and Preprocessing.

Electroencephalography (EEG) is among the most widely diffused, inexpensive, and adopted neuroimaging techniques. Nonetheless, EEG requires measurements against a reference site(s), which is typically chosen by the experimenter, and specific pre-processing steps precede analyses. It is therefore valuable to obtain quantities that are minimally affected by reference and pre-processing choices. Here, we show that the topological structure of embedding spaces, constructed either from multi-channel EEG timeseries or from their temporal structure, are subject-specific and robust to re-referencing and pre-processing pipelines. By contrast, the shape of correlation spaces, that is, discrete spaces where each point represents an electrode and the distance between them that is in turn related to the correlation between the respective timeseries, was neither significantly subject-specific nor robust to changes of reference. Our results suggest that the shape of spaces describing the observed configurations of EEG signals holds information about the individual specificity of the underlying individual's brain dynamics, and that temporal correlations constrain to a large degree the set of possible dynamics. In turn, these encode the differences between subjects' space of resting state EEG signals. Finally, our results and proposed methodology provide tools to explore the individual topographical landscapes and how they are explored dynamically. We propose therefore to augment conventional topographic analyses with an additional-topological-level of analysis, and to consider them jointly. More generally, these results provide a roadmap for the incorporation of topological analyses within EEG pipelines.

Selective Enhancement of Object Representations through Multisensory Integration.

Objects are the fundamental building blocks of how we create a representation of the external world. One major distinction among objects is between those that are animate versus those that are inanimate. In addition, many objects are specified by more than a single sense, yet the nature by which multisensory objects are represented by the brain remains poorly understood. Using representational similarity analysis of male and female human EEG signals, we show enhanced encoding of audiovisual objects when compared with their corresponding visual and auditory objects. Surprisingly, we discovered that the often-found processing advantages for animate objects were not evident under multisensory conditions. This was due to a greater neural enhancement of inanimate objects-which are more weakly encoded under unisensory conditions. Further analysis showed that the selective enhancement of inanimate audiovisual objects corresponded with an increase in shared representations across brain areas, suggesting that the enhancement was mediated by multisensory integration. Moreover, a distance-to-bound analysis provided critical links between neural findings and behavior. Improvements in neural decoding at the individual exemplar level for audiovisual inanimate objects predicted reaction time differences between multisensory and unisensory presentations during a Go/No-Go animate categorization task. Links between neural activity and behavioral measures were most evident at intervals of 100-200 ms and 350-500 ms after stimulus presentation, corresponding to time periods associated with sensory evidence accumulation and decision-making, respectively. Collectively, these findings provide key insights into a fundamental process the brain uses to maximize the information it captures across sensory systems to perform object recognition.SIGNIFICANCE STATEMENT Our world is filled with ever-changing sensory information that we are able to seamlessly transform into a coherent and meaningful perceptual experience. We accomplish this feat by combining different stimulus features into objects. However, despite the fact that these features span multiple senses, little is known about how the brain combines the various forms of sensory information into object representations. Here, we used EEG and machine learning to study how the brain processes auditory, visual, and audiovisual objects. Surprisingly, we found that nonliving (i.e., inanimate) objects, which are more difficult to process with one sense alone, benefited the most from engaging multiple senses.

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.

A computational model for grid maps in neural populations.

Grid cells in the entorhinal cortex, together with head direction, place, speed and border cells, are major contributors to the organization of spatial representations in the brain. In this work we introduce a novel theoretical and algorithmic framework able to explain the optimality of hexagonal grid-like response patterns. We show that this pattern is a result of minimal variance encoding of neurons together with maximal robustness to neurons' noise and minimal number of encoding neurons. The novelty lies in the formulation of the encoding problem considering neurons as an overcomplete basis (a frame) where the position information is encoded. Through the modern Frame Theory language, specifically that of tight and equiangular frames, we provide new insights about the optimality of hexagonal grid receptive fields. The proposed model is based on the well-accepted and tested hypothesis of Hebbian learning, providing a simplified cortical-based framework that does not require the presence of velocity-driven oscillations (oscillatory model) or translational symmetries in the synaptic connections (attractor model). We moreover demonstrate that the proposed encoding mechanism naturally explains axis alignment of neighbor grid cells and maps shifts, rotations and scaling of the stimuli onto the shape of grid cells' receptive fields, giving a straightforward explanation of the experimental evidence of grid cells remapping under transformations of environmental cues.

Electrocorticography Evidence of Tactile Responses in Visual Cortices.

There is ongoing debate regarding the extent to which human cortices are specialized for processing a given sensory input versus a given type of information, independently of the sensory source. Many neuroimaging and electrophysiological studies have reported that primary and extrastriate visual cortices respond to tactile and auditory stimulation, in addition to visual inputs, suggesting these cortices are intrinsically multisensory. In particular for tactile responses, few studies have proven neuronal processes in visual cortex in humans. Here, we assessed tactile responses in both low-level and extrastriate visual cortices using electrocorticography recordings in a human participant. Specifically, we observed significant spectral power increases in the high frequency band (30-100 Hz) in response to tactile stimuli, reportedly associated with spiking neuronal activity, in both low-level visual cortex (i.e. V2) and in the anterior part of the lateral occipital-temporal cortex. These sites were both involved in processing tactile information and responsive to visual stimulation. More generally, the present results add to a mounting literature in support of task-sensitive and sensory-independent mechanisms underlying functions like spatial, motion, and self-processing in the brain and extending from higher-level as well as to low-level cortices.

Kinematic and Somatosensory Gains in Infants with Cerebral Palsy After a Multi-Component Upper-Extremity Intervention: A Randomized Controlled Trial.

Upper extremity (UE) impairments in infants with cerebral palsy (CP) result from reduced quality of motor experiences and "noisy" sensory inputs. We hypothesized that a neuroscience-based multi-component intervention would improve somatosensory processing and motor measures of more-affected (UEs) in infants with CP and asymmetric UE neurologic impairments, while remaining safe for less-affected UEs. Our randomized controlled trial compared infants (6-24 months) with CP receiving intervention (N = 37) versus a waitlisted group (N = 36). Treatment effects tested a direct measurement of reach smoothness (3D-kinematics), a measure of unimanual fine motor function (Bayley unimanual fine motor raw scores), and EEG measures of cortical somatosensory processing. The four-week therapist-directed, parent-administered intervention included daily (1) bimanual play; (2) less-affected UE wearing soft-constraint (6 h/day, electronically-monitored); (3) reach training on more-affected UE; (4) graduated motor-sensory training; and (5) parent education. Waitlist infants received only bimanual play. Effectiveness and safety were tested; z-scores from 54 posttest-matched typically-developing infants provided benchmarks for treatment effects. Intervention and waitlist infants had no pretest differences. Median weekly constraint wear was 38 h; parent-treatment fidelity averaged > 92%. On the more affected side, the intervention significantly increased smoothness of reach (Cohen's d = - 0.90; p < .001) and unimanual fine motor skill (d = 0.35; p = .004). Using unadjusted p values, intervention improved somatosensory processing (d = 0.53; p = .04). All intervention effects referenced well to typically developing children. Safety of the intervention was demonstrated through positive- or non-effects on measurements involving the constrained, less-affected UE and gross motor function; unexpected treatment effects on reach smoothness occurred in less-affected UEs (d = - 0.85; p = .01). This large clinical trial demonstrated intervention effectiveness and safety for developing sensory and motor systems with improvements in reach smoothness, and developmental abilities.Clinical Trail Registration: ClinicalTrials.gov NCT02567630, registered October 5, 2015.

Neonatal Multisensory Processing in Preterm and Term Infants Predicts Sensory Reactivity and Internalizing Tendencies in Early Childhood.

Multisensory processes include the capacity to combine information from the different senses, often improving stimulus representations and behavior. The extent to which multisensory processes are an innate capacity or instead require experience with environmental stimuli remains debated. We addressed this knowledge gap by studying multisensory processes in prematurely born and full-term infants. We recorded 128-channel event-related potentials (ERPs) from a cohort of 55 full-term and 61 preterm neonates (at an equivalent gestational age) in response to auditory, somatosensory, and combined auditory-somatosensory multisensory stimuli. Data were analyzed within an electrical neuroimaging framework, involving unsupervised topographic clustering of the ERP data. Multisensory processing in full-term infants was characterized by a simple linear summation of responses to auditory and somatosensory stimuli alone, which furthermore shared common ERP topographic features. We refer to the ERP topography observed in full-term infants as "typical infantile processing" (TIP). In stark contrast, preterm infants exhibited non-linear responses and topographies less-often characterized by TIP; there were distinct patterns of ERP topographies to multisensory and summed unisensory conditions. We further observed that the better TIP characterized an infant's ERPs, independently of prematurity, the more typical was the score on the Infant/Toddler Sensory Profile (ITSP) at 12 months of age and the less likely was the child to the show internalizing tendencies at 24 months of age. Collectively, these results highlight striking differences in the brain's responses to multisensory stimuli in children born prematurely; differences that relate to later sensory and internalizing functions.

Encoding of Auditory Temporal Gestalt in the Human Brain.

The perception of an acoustic rhythm is invariant to the absolute temporal intervals constituting a sound sequence. It is unknown where in the brain temporal Gestalt, the percept emerging from the relative temporal proximity between acoustic events, is encoded. Two different relative temporal patterns, each induced by three experimental conditions with different absolute temporal patterns as sensory basis, were presented to participants. A linear support vector machine classifier was trained to differentiate activation patterns in functional magnetic resonance imaging data to the two different percepts. Across the sensory constituents the classifier decoded which percept was perceived. A searchlight analysis localized activation patterns specific to the temporal Gestalt bilaterally to the temporoparietal junction, including the planum temporale and supramarginal gyrus, and unilaterally to the right inferior frontal gyrus (pars opercularis). We show that auditory areas not only process absolute temporal intervals, but also integrate them into percepts of Gestalt and that encoding of these percepts persists in high-level associative areas. The findings complement existing knowledge regarding the processing of absolute temporal patterns to the processing of relative temporal patterns relevant to the sequential binding of perceptual elements into Gestalt.

Contributions of Intraindividual and Interindividual Differences to Multisensory Processes.

Most evidence on the neural and perceptual correlates of sensory processing derives from studies that have focused on only a single sensory modality and averaged the data from groups of participants. Although valuable, such studies ignore the substantial interindividual and intraindividual differences that are undoubtedly at play. Such variability plays an integral role in both the behavioral/perceptual realms and in the neural correlates of these processes, but substantially less is known when compared with group-averaged data. Recently, it has been shown that the presentation of stimuli from two or more sensory modalities (i.e., multisensory stimulation) not only results in the well-established performance gains but also gives rise to reductions in behavioral and neural response variability. To better understand the relationship between neural and behavioral response variability under multisensory conditions, this study investigated both behavior and brain activity in a task requiring participants to discriminate moving versus static stimuli presented in either a unisensory or multisensory context. EEG data were analyzed with respect to intraindividual and interindividual differences in RTs. The results showed that trial-by-trial variability of RTs was significantly reduced under audiovisual presentation conditions as compared with visual-only presentations across all participants. Intraindividual variability of RTs was linked to changes in correlated activity between clusters within an occipital to frontal network. In addition, interindividual variability of RTs was linked to differential recruitment of medial frontal cortices. The present findings highlight differences in the brain networks that support behavioral benefits during unisensory versus multisensory motion detection and provide an important view into the functional dynamics within neuronal networks underpinning intraindividual performance differences.

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.

Distinct brain representations of processed and unprocessed foods.

Among all of the stimuli surrounding us, food is arguably the most rewarding for the essential role it plays in our survival. In previous visual recognition research, it has already been demonstrated that the brain not only differentiates edible stimuli from non-edible stimuli but also is endowed with the ability to detect foods' idiosyncratic properties such as energy content. Given the contribution of the cooked diet to human evolution, in the present study we investigated whether the brain is sensitive to the level of processing food underwent, based solely on its visual appearance. We thus recorded visual evoked potentials (VEPs) from normal-weight healthy volunteers who viewed color images of unprocessed and processed foods equated in caloric content. Results showed that VEPs and underlying neural sources differed as early as 130 ms post-image onset when participants viewed unprocessed versus processed foods, suggesting a within-category early discrimination of food stimuli. Responses to unprocessed foods engaged the inferior frontal and temporal regions and the premotor cortices. In contrast, viewing processed foods led to the recruitment of occipito-temporal cortices bilaterally, consistently with other motivationally relevant stimuli. This is the first evidence of diverging brain responses to food as a function of the transformation undergone during its preparation that provides insights on the spatiotemporal dynamics of food recognition.

Randomized controlled trial protocol to improve multisensory neural processing, language and motor outcomes in preterm infants.

BACKGROUND: Premature infants are at risk for abnormal sensory development due to brain immaturity at birth and atypical early sensory experiences in the Neonatal Intensive Care Unit. This altered sensory development can have downstream effects on other more complex developmental processes. There are currently no interventions that address rehabilitation of sensory function in the neonatal period. METHODS: This study is a randomized controlled trial of preterm infants enrolled at 32-36 weeks postmenstrual age to either standard care or standard care plus multisensory intervention in order to study the effect of multisensory intervention as compared to standard care alone. The study population will consist of 100 preterm infants in each group (total n = 200). Both groups will receive standard care, consisting of non-contingent recorded parent's voice and skin-to-skin by parent. The multisensory group will also receive contemporaneous holding and light pressure containment for tactile stimulation, playing of the mother's voice contingent on the infant's pacifier sucking for auditory stimulation, exposure to a parent-scented cloth for olfactory stimulation, and exposure to carefully regulated therapist breathing that is mindful and responsive to the child's condition for vestibular stimulation. The primary outcome is a brain-based measure of multisensory processing, measured using time locked-EEG. Secondary outcomes include sensory adaptation, tactile processing, speech sound differentiation, motor and language function, measured at one and two years corrected gestational age. DISCUSSION: This is the first randomized controlled trial of a multisensory intervention using brain-based measurements in order to explain the causal effects of the multisensory intervention on neural processing changes to mediate neurodevelopmental outcomes in former preterm infants. In addition to contributing a critical link in our understanding of these processes, the protocolized multisensory intervention in this study is therapist administered, parent supported and leverages simple technology. Thus, this multisensory intervention has the potential to be widely implemented in various NICU settings, with the opportunity to potentially improve neurodevelopment of premature infants. TRIAL REGISTRATION: NIH Clinical Trials ( clinicaltrials.gov ): NCT03232931 . Registered July 2017.

Brain mechanisms for perceiving illusory lines in humans.

Illusory contours (ICs) are perceptions of visual borders despite absent contrast gradients. The psychophysical and neurobiological mechanisms of IC processes have been studied across species and diverse brain imaging/mapping techniques. Nonetheless, debate continues regarding whether IC sensitivity results from a (presumably) feedforward process within low-level visual cortices (V1/V2) or instead are processed first within higher-order brain regions, such as lateral occipital cortices (LOC). Studies in animal models, which generally favour a feedforward mechanism within V1/V2, have typically involved stimuli inducing IC lines. By contrast, studies in humans generally favour a mechanism where IC sensitivity is mediated by LOC and have typically involved stimuli inducing IC forms or shapes. Thus, the particular stimulus features used may strongly contribute to the model of IC sensitivity supported. To address this, we recorded visual evoked potentials (VEPs) while presenting human observers with an array of 10 inducers within the central 5°, two of which could be oriented to induce an IC line on a given trial. VEPs were analysed using an electrical neuroimaging framework. Sensitivity to the presence vs. absence of centrally-presented IC lines was first apparent at ∼200 ms post-stimulus onset and was evident as topographic differences across conditions. We also localized these differences to the LOC. The timing and localization of these effects are consistent with a model of IC sensitivity commencing within higher-level visual cortices. We propose that prior observations of effects within lower-tier cortices (V1/V2) are the result of feedback from IC sensitivity that originates instead within higher-tier cortices (LOC).

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.