Preterm infants show an atypical processing of the mother's voice.

To understand the consequences of prematurity on language perception, it is fundamental to determine how atypical early sensory experience affects brain development. At term equivalent age, ten preterm and ten full-term newborns underwent high-density EEG during mother or stranger speech presentation, in the forward or backward order. A general group effect terms > preterms is evident in the theta frequency band, in the left temporal area, with preterms showing significant activation for strangers' and terms for the mother's voice. A significant group contrast in the low and high theta in the right temporal regions indicates higher activations for the stranger's voice in preterms. Finally, only full terms presented a late gamma band increase for the maternal voice, indicating a more mature brain response. EEG time-frequency analysis demonstrate that preterm infants are selectively responsive to stranger voices in both temporal hemispheres, and that they lack selective brain responses to their mother's forward voice.

Deficient Novelty Detection and Encoding in Early Alzheimer's Disease: An ERP Study.

Patients with early Alzheimer's disease (AD) have difficulty in learning new information and in detecting novel stimuli. The underlying physiological mechanisms are not well known. We investigated the electrophysiological correlates of the early (< 400 ms), automatic phase of novelty detection and encoding in AD. We used high-density EEG Queryin patients with early AD and healthy age-matched controls who performed a continuous recognition task (CRT) involving new stimuli (New), thought to provoke novelty detection and encoding, which were then repeated up to 4 consecutive times to produce over-familiarity with the stimuli. Stimuli then reappeared after 9-15 intervening items (N-back) to be re-encoded. AD patients had substantial difficulty in detecting novel stimuli and recognizing repeated ones. Main evoked potential differences between repeated and new stimuli emerged at 180-260 ms: neural source estimations in controls revealed more extended MTL activation for N-back stimuli and anterior temporal lobe activations for New stimuli compared to highly familiar repetitions. In contrast, AD patients exhibited no activation differences between the three stimulus types. In direct comparison, healthy subjects had significantly stronger MTL activation in response to New and N-back stimuli than AD patients. These results point to abnormally weak early MTL activity as a correlate of deficient novelty detection and encoding in early AD.

Shedding light on excessive crying in babies.

BACKGROUND: Excessive and inconsolable crying behavior in otherwise healthy infants (a condition called infant colic (IC)) is very distressing to parents, may lead to maternal depression, and in extreme cases, may result in shaken baby syndrome. Despite the high prevalence of this condition (20% of healthy infants), the underlying neural mechanisms of IC are still unknown. METHODS: By employing the latest magnetic resonance imaging (MRI) techniques in newborns, we prospectively investigated whether newborns' early brain responses to a sensory stimulus (smell) is associated with a subsequent crying behavior. RESULTS: In our sample population of 21 healthy breastfed newborns, those who developed IC at 6 weeks exhibited brain activation and functional connectivity in primary and secondary olfactory brain areas that were distinct from those in babies that did not develop IC. Different activation in brain regions known to be involved in sensory integration was also observed in colicky babies. These responses measured shortly after birth were highly correlated with the mean crying time at 6 weeks of age. CONCLUSIONS: Our results offer novel insights into IC pathophysiology by demonstrating that, shortly after birth, the central nervous system of babies developing IC has already greater reactivity to sensory stimuli than that of their noncolicky peers. IMPACT: Shortly after birth, the central nervous system of colicky infants has a greater sensitivity to olfactory stimuli than that of their noncolicky peers. This early sensitivity explains as much as 48% of their subsequent crying behavior at 6 weeks of life. Brain activation patterns to olfactory stimuli in colicky infants include not only primary olfactory areas but also brain regions involved in pain processing, emotional valence attribution, and self-regulation. This study links earlier findings in fields as diverse as gastroenterology and behavioral psychology and has the potential of helping healthcare professionals to define strategies to advise families.

Neural Correlates of Voice Perception in Newborns and the Influence of Preterm Birth.

Maternal voice is a highly relevant stimulus for newborns. Adult voice processing occurs in specific brain regions. Voice-specific brain areas in newborns and the relevance of an early vocal exposure on these networks have not been defined. This study investigates voice perception in newborns and the impact of prematurity on the cerebral processes. Functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) were used to explore the brain responses to maternal and stranger female voices in full-term newborns and preterm infants at term-equivalent age (TEA). fMRI results and the EEG oddball paradigm showed enhanced processing for voices in preterms at TEA than in full-term infants. Preterm infants showed additional cortical regions involved in voice processing in fMRI and a late mismatch response for maternal voice, considered as a first trace of a recognition process based on memory representation. Full-term newborns showed increased cerebral activity to the stranger voice. Results from fMRI, oddball, and standard auditory EEG paradigms highlighted important change detection responses to novelty after birth. These findings suggest that the main components of the adult voice-processing networks emerge early in development. Moreover, an early postnatal exposure to voices in premature infants might enhance their capacity to process voices.

Music enhances structural maturation of emotional processing neural pathways in very preterm infants.

Prematurity disrupts brain maturation by exposing the developing brain to different noxious stimuli present in the neonatal intensive care unit (NICU) and depriving it from meaningful sensory inputs during a critical period of brain development, leading to later neurodevelopmental impairments. Musicotherapy in the NICU environment has been proposed to promote sensory stimulation, relevant for activity-dependent brain plasticity, but its impact on brain structural maturation is unknown. Neuroimaging studies have demonstrated that music listening triggers neural substrates implied in socio-emotional processing and, thus, it might influence networks formed early in development and known to be affected by prematurity. Using multi-modal MRI, we aimed to evaluate the impact of a specially composed music intervention during NICU stay on preterm infant's brain structure maturation. 30 preterm newborns (out of which 15 were exposed to music during NICU stay and 15 without music intervention) and 15 full-term newborns underwent an MRI examination at term-equivalent age, comprising diffusion tensor imaging (DTI), used to evaluate white matter maturation using both region-of-interest and seed-based tractography approaches, as well as a T2-weighted image, used to perform amygdala volumetric analysis. Overall, WM microstructural maturity measured through DTI metrics was reduced in preterm infants receiving the standard-of-care in comparison to full-term newborns, whereas preterm infants exposed to the music intervention demonstrated significantly improved white matter maturation in acoustic radiations, external capsule/claustrum/extreme capsule and uncinate fasciculus, as well as larger amygdala volumes, in comparison to preterm infants with standard-of-care. These results suggest a structural maturational effect of the proposed music intervention on premature infants' auditory and emotional processing neural pathways during a key period of brain development.

Early vocal contact and music in the NICU: new insights into preventive interventions.

It is now clearly established that the environment and the sensory stimuli, particularly during the perinatal period, have an impact on infant's development. During the last trimester of gestation, activity-dependent plasticity shapes the fetal brain, and prematurity has been shown to alter the typical developmental trajectories. In this delicate period, preventive interventions aiming at modulating these developmental trajectories through activity-inducing interventions are currently underway to be tested. The purpose of this review paper is to describe the potentialities of early vocal contact and music on the preterm infant's brain development, and their potential beneficial effect on early development. Scientific evidence supports a behavioral orientation of the newborn to organized sounds, such as those of voice and music, and recent neuroimaging studies further confirm full cerebral processing of music as multisensory stimuli. However, the impact of long-term effects of music exposure and early vocal contact on preterm infants' long-term neurodevelopment needs be further investigated. To conclude, it is necessary to establish the neuroscientific bases of the early perception and the long-term effects of music and early vocal contact on the premature newborns' development. Scientific projects are currently on the way to fill this gap in knowledge.

Absence of an early hippocampal encoding signal after medial temporal lesions: No consequence for the spacing effect.

Immediately repeated meaningful pictures in a continuous recognition task induce a positive frontal potential at about 200-300 ms, which appears to emanate from the medial temporal lobe (MTL) centered on the hippocampus, as concluded from inverse solutions, coherence measurements, and depth electrode recordings in humans. In this study, we tested patients with unilateral MTL lesions due to stroke to verify the provenance of this signal and its association with the spacing effect (SE)-the improved learning of material encountered in spaced rather than massed presentation. We found that unilateral left or right MTL lesions abolished the early frontal MTL-mediated signal but not the spacing effect. We conclude that the SE does not depend on MTL integrity. We suggest that the early frontal signal at 200-300 ms after immediate picture repetition may serve as a direct biomarker of MTL integrity that may be useful in the early stages of diseases like Alzheimer's.

fMRI-based Neuronal Response to New Odorants in the Newborn Brain.

The sense of smell is one of the oldest and the most primitive senses mammals possess, it helps to evaluate the surrounding environment. From birth, smell is an important sensory modality, highly relevant for neonatal behavioral adaptation. Even though human newborns seem to be able to perceive and react to olfactory stimuli, there is still a lack of knowledge about the ontogeny of smell and the underlying central processing involved in odor perception in newborns. Brain networks involved in chemosensory perception of odorants are well described in adults, however in newborns there is no evidence that central olfaction is functional given the largely unmyelinated neonatal central nervous system. To examine this question, we used functional magnetic resonance imaging (fMRI) in the newborn to characterize cortical response to olfactory and trigeminal odorants. Here we show that brain response to odors can be measured and localized using functional MRI in newborns. Furthermore, we found that the developing brain, only few days after birth, processes new artificial odorants in similar cortical areas than adults, including piriform cortex, orbitofrontal cortex and insula. Our work provides evidence that human olfaction at birth relies on brain functions that involve all levels of the cortical olfactory system.

Anatomical and functional predictors of disorientation after first-ever brain damage.

BACKGROUND AND OBJECTIVES: Disorientation is a frequent consequence of acute brain injury or diffuse disorders, such as confusional states or dementia. Its anatomical correlates are debated. Impaired memory as its commonly assumed mechanism predicts that disorientation is associated with medial temporal damage. The alternative is that disorientation reflects defective orbitofrontal reality filtering (ORFi) - a specific failure to identify whether thoughts or memories refer to present reality or not. The latter is a function of the posterior orbitofrontal cortex and connected structures. This study examined the mechanisms and anatomical basis of disorientation in an unselected group of patients with first-ever subacute brain injury. METHODS: Participants hospitalized for neurorehabilitation were asked to participate in this observational cohort study if they had first-ever organic hemispheric brain dysfunction as evident in a localizable brain lesion or verbal amnesia (often without localizable brain damage). Orientation to time, place, situation and person was tested with a 20-items questionnaire. To identify the mechanisms of disorientation, we determined its correlations with executive tasks, verbal episodic memory, and ORFi in all patients. ORFi was examined with a continuous recognition task, which measures learning and item recognition in the first run, and ORFi as reflected in the increase of false positive responses in the second run (temporal context confusion). Lesions of patients having localizable brain damage were manually delineated and normalized before entering multivariate lesion-symptom-mapping (LSM) to determine anatomical predictors of orientation. RESULTS: Eighty-four patients (61.1 ± 14.4 years, 29 women) were included. Among measures of memory and executive functioning, a step-wise regression retained temporal context confusion (R = -0.71, p < 0.0001), item recognition (R = 0.67, p < 0.0001) and delayed free recall (R = 0.63, p < 0.0001) as significant predictors of orientation. LSM was possible in 67 participants; it revealed an association of disorientation with damage of the right OFC and the bilateral head of the caudate nucleus. CONCLUSION: Disorientation in non-confused, non-demented patients with first-ever brain damage is associated with impaired orbitofrontal reality filtering and memory dysfunction, but not with executive dysfunction. Its main anatomical determinant is damage to the orbitofrontal cortex and its subcortical relay, the head of the caudate.

Flexible adjustment of anticipations in human outcome processing.

To sense whether thoughts refer to current reality or not, a capacity called orbitofrontal reality filtering, depends on an orbitofrontal signal when anticipated outcomes fail to occur. Here, we explored the flexibility and precision of outcome processing in a deterministic reversal learning task. Healthy subjects decided which one of two colored squares hid a target stimulus. Brain activity was measured with high-density electroencephalography. Stimuli resembling, but not identical with, the target stimuli were initially processed like different stimuli from 210 to 250 ms, irrespective of behavioral relevance. From 250 ms on, they were processed according to behavioral relevance: If they required a subsequent switch, they were processed like different stimuli; if they had been declared potential targets, they were treated like true targets. Stimuli requiring a behavioral switch induced strong theta activity in orbitofrontal, ventromedial, and medial temporal regions. The study indicates flexible adaptation of anticipations but precise processing of outcomes, mainly determined by behavioral relevance.

Distinct outcome processing in deterministic and probabilistic reversal learning.

Anticipations that fail to happen are important drivers of behavioral adaptation. Their processing appears to depend on the context. In a deterministic environment, where a stimulus unequivocally predicts the outcome, processing of absent outcomes involves the posterior orbitofrontal cortex (OFC). Failure has been linked to reality confusion with confabulations and disorientation. In a probabilistic environment, absent outcomes appear to be processed by the anterior cingulate cortex (ACC) rather than the OFC. Failure has been associated with poor decision making and schizophrenia. These data suggest different mechanisms depending on the context. Here, healthy human subjects made two formally similar reversal learning tasks, but one with deterministic, the other with probabilistic instructions. Brain activity was monitored using high-density electroencephalography. We found that in the deterministic task, negative outcomes, which unequivocally call for a behavioral switch, induced a distinct frontal potential at 200-300 msec. Computational modeling indicated a strong association of evoked potentials with prediction error, surprise, and behavioral adaptation. In the probabilistic task, where behavioral adaptation follows the cumulated processing of outcomes, negative outcomes evoked potentials that were associated with prediction error and surprise, but had a weak link with subsequent behavior. Outcome processing in the probabilistic task induced stronger activation than the deterministic task of an extended network including the ACC, OFC and striatum at 300-400 msec. In both tasks, negative outcomes were processed differently from positive outcomes at 400-600 msec, possibly reflecting updating of the outcome record. We conclude that the brain disposes of at least two distinct systems processing outcomes with unequivocal or ambiguous behavioral significance. These systems differ along behavioral, clinical, electrophysiological and anatomical dimensions.

Rapid Sequential Implication of the Human Medial Temporal Lobe in Memory Encoding and Recognition.

The medial temporal lobe (MTL) is crucial for memory encoding and recognition. The time course of these processes is unknown. The present study juxtaposed encoding and recognition in a single paradigm. Twenty healthy subjects performed a continuous recognition task as brain activity was monitored with a high-density electroencephalography. The task presented New pictures thought to evoke encoding. The stimuli were then repeated up to 4 consecutive times to produce over-familiarity. These repeated stimuli served as "baseline" for comparison with the other stimuli. Stimuli later reappeared after 9-15 intervening items, presumably associated with new encoding and recognition. Encoding-related differences in evoked response potential amplitudes and in spatiotemporal analysis were observed at 145-300 ms, whereby source estimation indicated MTL and orbitofrontal activity from 145 to 205 ms. Recognition-related activity evoked by late repetitions occurred at 405-470 ms, implicating the MTL and neocortical structures. These findings indicate that encoding of information is initiated before it is recognized. The result helps to explain modifications of memories over time, including false memories, confabulation, and consolidation.