Amygdala hyperactivation relates to eating behaviour: a potential indicator of food addiction in Prader-Willi syndrome.

Prader-Willi syndrome is a rare neurodevelopmental genetic disorder characterized by various endocrine, cognitive and behavioural problems. The symptoms include an obsession for food and reduced satiety, which leads to hyperphagia and morbid obesity. Neuropsychological studies have reported that Prader-Willi patients display altered social interactions with a specific weakness in interpreting social information and responding to them, a symptom close to that observed in autism spectrum disorders. In the present case-control study, we hypothesized that brain regions associated with compulsive eating behaviour would be abnormally activated by food-related odours in Prader-Willi syndrome, as these can stimulate the appetite and induce hunger-related behaviour. We conducted a brain imaging study using the olfactory modality because odours have a high-hedonic valence and can cause stronger emotional reactions than other modalities. Further, the olfactory system is also intimately associated with the endocrine regulation of energy balance and is the most appropriate modality for studies of Prader-Willi syndrome. A total of 16 Prader-Willi participants were recruited for this study, which is a significant achievement given the low incidence rate of this rare disease. The second group of 11 control age-matched subjects also participated in the brain imaging study. In the MRI scanner, using an MRI-compatible olfactometer during 56 block sessions, we randomly presented two odours (tulip and caramel), which have different hedonic valence and a different capacity to arouse hunger-related behaviour. Our results demonstrate that Prader-Willi participants have abnormal activity in the brain reward system that regulates eating behaviour. Indeed, we found that these patients had right amygdala activity up to five times higher in response to a food odour (caramel) compared with the tulip odour. In contrast, age-matched control participants had similar activity levels in response to both odours. The amygdala activity levels were found to be associated with the severity of the hyperphagia in Prader-Willi patients. Our results provide evidence for functional alteration of the right amygdala in Prader-Willi syndrome, which is part of the brain network involved in food addiction modulated by the ghrelin and oxytocin systems, which may drive the hyperphagia. Our study provides important new insights into the functioning of emotion-related brain circuits and pathology, and it is one of the few to explore the dysfunction of the neural circuits involved in emotion and addiction in Prader-Willi syndrome. It suggests new directions for the exploration and remediation of addictive behaviours.

Brain plasticity and auditory spatial adaptation in patients with unilateral hearing loss.

The ability to localize sounds in patients with Unilateral Hearing Loss (UHL) is usually disrupted due to alteration in the integration of binaural cues. Nonetheless, some patients are able to compensate deficit using adaptive strategies. In this study, we explored the neural correlates underlying this adaptation. Twenty-one patients with UHL were separated into 3 groups using cluster analysis based on their binaural performance. The resulting clusters were referred to as better, moderate, and poorer performers cluster (BPC, MPC, and PPC). We measured the mismatch negativity (MMN) elicited by deviant sounds located at 10°, 20°, and 100° from a standard positioned at 50° ipsilateral to the deaf ear. The BPC exhibited significant MMN for all 3 deviants, similar to normal hearing (NH) subjects. In contrast, there was no significant MMN for 10° and 20° deviants for the PPC and for NH when one ear was plugged and muffed. Scalp distribution was maximal over central regions in BPC, while PPC showed more frontal MMN distribution. Thus, the BPC exhibited a contralateral activation pattern, similar to NH, while the PPC exhibited more symmetrical hemispheric activation. MMN can be used as a neural marker to reflect spatial adaptation in patients with UHL.

Auditory cortical plasticity after cochlear implantation in asymmetric hearing loss is related to spatial hearing: a PET H215O study.

In asymmetric hearing loss (AHL), the normal pattern of contralateral hemispheric dominance for monaural stimulation is modified, with a shift towards the hemisphere ipsilateral to the better ear. The extent of this shift has been shown to relate to sound localization deficits. In this study, we examined whether cochlear implantation to treat postlingual AHL can restore the normal functional pattern of auditory cortical activity and whether this relates to improved sound localization. The auditory cortical activity was found to be lower in the AHL cochlear implanted (AHL-CI) participants. A cortical asymmetry index was calculated and showed that a normal contralateral dominance was restored in the AHL-CI patients for the nonimplanted ear, but not for the ear with the cochlear implant. It was found that the contralateral dominance for the nonimplanted ear strongly correlated with sound localization performance (rho = 0.8, P < 0.05). We conclude that the reorganization of binaural mechanisms in AHL-CI subjects reverses the abnormal lateralization pattern induced by the deafness, and that this leads to improved spatial hearing. Our results suggest that cochlear implantation enables the reconstruction of the cortical mechanisms of spatial selectivity needed for sound localization.

Functional Reorganization of the Central Auditory System in Children with Single-Sided Deafness: A Protocol Using fNIRS.

In children, single-sided deafness (SSD) affects the development of linguistic and social skills and can impede educational progress. These difficulties may relate to cortical changes that occur following SSD, such as reduced inter-hemispheric functional asymmetry and maladaptive brain plasticity. To investigate these neuronal changes and their evolution in children, a non-invasive technique is required that is little affected by motion artifacts. Here, we present a research protocol that uses functional near-infrared spectroscopy (fNIRS) to evaluate the reorganization of cortical auditory asymmetry in children with SSD; it also examines how the cortical changes relate to auditory and language skills. The protocol is designed for children whose SSD has not been treated, because hearing restoration can alter both brain reorganization and behavioral performance. We propose a single-center, cross-sectional study that includes 30 children with SSD (congenital or acquired moderate-to-profound deafness) and 30 children with normal hearing (NH), all aged 5-16 years. The children undergo fNIRS during monaural and binaural stimulation, and the pattern of cortical activity is analyzed using measures of the peak amplitude and area under the curve for both oxy- and deoxyhemoglobin. These cortical measures can be compared between the two groups of children, and analyses can be run to determine whether they relate to binaural hearing (speech-in-noise and sound localization), speech perception and production, and quality of life (QoL). The results could be of relevance for developing individualized rehabilitation programs for SSD, which could reduce patients' difficulties and prevent long-term neurofunctional and clinical consequences.

Intensity patterns at the peaks of brain activity in fMRI and PET are highly correlated with neural models of spatial integration.

Spatial integration during the brain's cognitive activity prompts changes in energy used by different neuroglial populations. Nevertheless, the organisation of such integration in 3D -brain activity remains undescribed from a quantitative standpoint. In response, we applied a cross-correlation between brain activity and integrative models, which yielded a deeper understanding of information integration in functional brain mapping. We analysed four datasets obtained via fundamentally different neuroimaging techniques (functional magnetic resonance imaging [fMRI] and positron emission tomography [PET]) and found that models of spatial integration with an increasing input to each step of integration were significantly more correlated with brain activity than models with a constant input to each step of integration. In addition, marking the voxels with the maximal correlation, we found exceptionally high intersubject consistency with the initial brain activity at the peaks. Our method demonstrated for the first time that the network of peaks of brain activity is organised strictly according to the models of spatial integration independent of neuroimaging techniques. The highest correlation with models integrating an increasing at each step input suggests that brain activity reflects a network of integrative processes where the results of integration in some neuroglial populations serve as an input to other neuroglial populations.

Supra-normal skills in processing of visuo-auditory prosodic information by cochlear-implanted deaf patients.

Cochlear implanted (CI) adults with acquired deafness are known to depend on multisensory integration skills (MSI) for speech comprehension through the fusion of speech reading skills and their deficient auditory perception. But, little is known on how CI patients perceive prosodic information relating to speech content. Our study aimed to identify how CI patients use MSI between visual and auditory information to process paralinguistic prosodic information of multimodal speech and the visual strategies employed. A psychophysics assessment was developed, in which CI patients and hearing controls (NH) had to distinguish between a question and a statement. The controls were separated into two age groups (young and aged-matched) to dissociate any effect of aging. In addition, the oculomotor strategies used when facing a speaker in this prosodic decision task were recorded using an eye-tracking device and compared to controls. This study confirmed that prosodic processing is multisensory but it revealed that CI patients showed significant supra-normal audiovisual integration for prosodic information compared to hearing controls irrespective of age. This study clearly showed that CI patients had a visuo-auditory gain more than 3 times larger than that observed in hearing controls. Furthermore, CI participants performed better in the visuo-auditory situation through a specific oculomotor exploration of the face as they significantly fixate the mouth region more than young NH participants who fixate the eyes, whereas the aged-matched controls presented an intermediate exploration pattern equally reported between the eyes and mouth. To conclude, our study demonstrated that CI patients have supra-normal skills MSI when integrating visual and auditory linguistic prosodic information, and a specific adaptive strategy developed as it participates directly in speech content comprehension.

When two is worse than one: The deleterious impact of multisensory stimulation on response inhibition.

Multisensory facilitation is known to improve the perceptual performances and reaction times of participants in a wide range of tasks, from detection and discrimination to memorization. We asked whether a multimodal signal can similarly improve action inhibition using the stop-signal paradigm. Indeed, consistent with a crossmodal redundant signal effect that relies on multisensory neuronal integration, the threshold for initiating behavioral responses is known for being reached faster with multisensory stimuli. To evaluate whether this phenomenon also occurs for inhibition, we compared stop signals in unimodal (human faces or voices) versus audiovisual modalities in natural or degraded conditions. In contrast to the expected multisensory facilitation, we observed poorer inhibition efficiency in the audiovisual modality compared with the visual and auditory modalities. This result was corroborated by both response probabilities and stop-signal reaction times. The visual modality (faces) was the most effective. This is the first demonstration of an audiovisual impairment in the domain of perception and action. It suggests that when individuals are engaged in a high-level decisional conflict, bimodal stimulation is not processed as a simple multisensory object improving the performance but is perceived as concurrent visual and auditory information. This absence of unity increases task demand and thus impairs the ability to revise the response.

Evidence of a functional reorganization in the auditory dorsal stream following unilateral hearing loss.

Unilateral hearing loss (UHL) generates a disruption of binaural hearing mechanisms, which impairs sound localization and speech understanding in noisy environments. We conducted an original study using fMRI and psychoacoustic assessments to investigate the relationships between the extent of cortical reorganization across the auditory areas for UHL patients, the severity of unilateral hearing loss, and the deficit in binaural abilities. Twenty-eight volunteers (14 UHL patients) were recruited (twenty-two females and six males). The brain imaging analysis demonstrated that UHL induces a shift in aural dominance favoring the better ear, with a cortical reorganization located in the non-primary auditory areas, ipsilateral (same side) to the better ear. This reorganization is correlated not only to the hearing loss severity but also to spatial localization abilities. A regression analysis between brain activity and patient's performance clearly showed that the spatial hearing deficit was linked to a functional alteration of the posterior auditory areas known to process spatial hearing. Altogether, our study reveals that UHL alters the dorsal auditory stream, which is deleterious to spatial hearing.

Stimulus-specific information is represented as local activity patterns across the brain.

Modern neuroimaging represents three-dimensional brain activity, which varies across brain regions. It remains unknown whether activity of different brain regions has similar spatial organization to reflect similar cognitive processes. We developed a rotational cross-correlation method allowing a straightforward analysis of spatial activity patterns distributed across the brain in stimulation specific contrast images. Results of this method were verified using several statistical approaches on real and simulated random datasets. We found, for example, that the seed patterns in the fusiform face area were robustly correlated to brain regions involved in face-specific representations. These regions differed from the non-specific visual network meaning that activity structure in the brain is locally preserved in stimulus-specific regions. Our findings indicate spatially correlated perceptual representations in cerebral activity and suggest that the 3D coding of the processed information is organized using locally preserved activity patterns across the brain. More generally, our results demonstrate that information is represented and shared in the local spatial configurations of brain activity.

In vivo localization of cortical areas using a 3D computerized atlas of the marmoset brain.

We created a volumetric template of the marmoset (Callithrix jacchus) brain, which enables localization of the cortical areas defined in the Paxinos et al. (The marmoset brain in stereotaxic coordinates. Elsevier Academic Press, Cambridge, 2012) marmoset brain atlas, as well as seven broader cortical regions (occipital, temporal, parietal, prefrontal, motor, limbic, insular), different brain compartments (white matter, gray matter, cerebro-spinal fluid including ventricular spaces), and various other structures (brain stem, cerebellum, olfactory bulb, hippocampus). The template was designed from T1-weighted MR images acquired using a 3 T MRI scanner. It was based on a single fully segmented marmoset brain image, which was transported onto the mean of 13 adult marmoset brain images using a diffeomorphic strategy that fully preserves the brain topology. In addition, we offer an automatic segmentation pipeline which fully exploits the proposed template. The segmentation pipeline was quantitatively assessed by comparing the results of manual and automated segmentations. An associated program, written in Python, can be used from a command-line interface, or used interactively as a module of the 3DSlicer software. This program can be applied to the analysis of multimodal images, to map specific cortical areas in lesions or to define the seeds for further tractography analyses.

Categorization of everyday sounds by cochlear implanted children.

Auditory categorization is an important process in the perception and understanding of everyday sounds. The use of cochlear implants (CIs) may affect auditory categorization and result in poor abilities. The current study was designed to compare how children with normal hearing (NH) and children with CIs categorize a set of everyday sounds. We tested 24 NH children and 24 children with CI on a free-sorting task of 18 everyday sounds corresponding to four a priori categories: nonlinguistic human vocalizations, environmental sounds, musical sounds, and animal vocalizations. Multiple correspondence analysis revealed considerable variation within both groups of child listeners, although the human vocalizations and musical sounds were similarly categorized. In contrast to NH children, children with CIs categorized some sounds according to their acoustic content rather than their associated semantic information. These results show that despite identification deficits, children with CIs are able to categorize environmental and vocal sounds in a similar way to NH children, and are able to use categorization as an adaptive process when dealing with everyday sounds.

Categorisation of natural sounds at different stages of auditory recovery in cochlear implant adult deaf patients.

Previous studies have demonstrated that cochlear implant (CI) patients are more efficient at performing sound categorisation than sound identification. However, it remains unclear how this categorisation capacity develops with time during the rehabilitation period after implantation. To investigate the role of the post-implantation auditory experience in the broad sound categorisation in CI patients, we recruited CI patients with different durations of CI experience: Newly implanted CI patients (less than six months), Intermediate CI patients (6-14 months) and Experienced CI patients with a duration of implantation greater than 14 months. The patients completed a Free Sorting Task (FST), which allowed them to categorise 16 natural sounds based on their own criteria. We found an early deficit in categorisation, especially for vocal sounds; the categorisation started to improve after approximately six months post-implantation with a change of categorisation strategy which relied on different acoustic cues as a function of time after CI. The separation of the category of vocal sounds from other sounds significantly increased between the Newly implanted and Intermediate groups, i.e. as experience with the cochlear implant was acquired. The categorisation accuracy of vocal sounds was significantly correlated with the post-implantation period only in the group of newly implanted CI patients. This is the first study to show that the categorisation of vocal sounds with respect to non-vocal sounds improves during the rehabilitation period post-implantation. The first six-month post-implantation period appears to be crucial in this process. Our results demonstrate that patients in different rehabilitation periods use different acoustic cues, which increase their complexity with the CI experience.

Speech-in-noise perception in unilateral hearing loss: Relation to pure-tone thresholds and brainstem plasticity.

We investigated speech recognition in noise in subjects with mild to profound levels of unilateral hearing loss. Thirty-five adults were evaluated using an adaptive signal-to-noise ratio (SNR50) sentence recognition threshold test in three spatial configurations. The results revealed a significant correlation between pure-tone average audiometric thresholds in the poorer ear and SNR thresholds in the two conditions where speech and noise were spatially separated: dichotic - with speech presented to the poorer ear and reverse dichotic - with speech presented to the better ear. This first result suggested that standard pure-tone air-conduction thresholds can be a reliable predictor of speech recognition in noise for binaural conditions. However, a subgroup of 14 subjects was found to have poorer-than-expected speech recognition scores, especially in the reverse dichotic listening condition. In this subgroup 9 subjects had been diagnosed with vestibular schwannoma at stage III or IV likely affecting the lower brainstem function. These subjects showed SNR thresholds in the reverse dichotic condition on average 4dB poorer (higher) than for the other 21 normally-performing subjects. For the 7 of 9 subjects whose vestibular schwannoma was removed, the deficit was no longer apparent on average 5 months following the surgical procedure. These results suggest that following unilateral hearing loss the capacity to use monaural spectral information is supported by the lower brainstem.

Crossmodal interactions during non-linguistic auditory processing in cochlear-implanted deaf patients.

Due to signal distortion, speech comprehension in cochlear-implanted (CI) patients relies strongly on visual information, a compensatory strategy supported by important cortical crossmodal reorganisations. Though crossmodal interactions are evident for speech processing, it is unclear whether a visual influence is observed in CI patients during non-linguistic visual-auditory processing, such as face-voice interactions, which are important in social communication. We analyse and compare visual-auditory interactions in CI patients and normal-hearing subjects (NHS) at equivalent auditory performance levels. Proficient CI patients and NHS performed a voice-gender categorisation in the visual-auditory modality from a morphing-generated voice continuum between male and female speakers, while ignoring the presentation of a male or female visual face. Our data show that during the face-voice interaction, CI deaf patients are strongly influenced by visual information when performing an auditory gender categorisation task, in spite of maximum recovery of auditory speech. No such effect is observed in NHS, even in situations of CI simulation. Our hypothesis is that the functional crossmodal reorganisation that occurs in deafness could influence nonverbal processing, such as face-voice interaction; this is important for patient internal supramodal representation.

Deficits in voice and multisensory processing in patients with Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental and genetic disorder that is characterized by various expression of endocrine, cognitive and behavioral problems, among which a true obsession for food and a deficit of satiety that leads to hyperphagia and severe obesity. Neuropsychological studies have reported that PWS display altered social interactions with a specific weakness in interpreting social information and in responding to them, a symptom closed to that observed in autism spectrum disorders (ASD). Based on the hypothesis that atypical multisensory integration such as face and voice interactions would contribute in PWS to social impairment we investigate the abilities of PWS to process communication signals including the human voice. Patients with PWS recruited from the national reference center for PWS performed a simple detection task of stimuli presented in an uni-o or bimodal condition, as well as a voice discrimination task. Compared to control typically developing (TD) individuals, PWS present a specific deficit in discriminating human voices from environmental sounds. Further, PWS present a much lower multisensory benefits with an absence of violation of the race model indicating that multisensory information do not converge and interact prior to the initiation of the behavioral response. All the deficits observed in PWS were stronger for the subgroup of patients suffering from Uniparental Disomy, a population known to be more sensitive to ASD. Altogether, our study suggests that the deficits in social behavior observed in PWS derive at least partly from an impairment in deciphering the social information carried by voice signals, face signals, and the combination of both. In addition, our work is in agreement with the brain imaging studies revealing an alteration in PWS of the "social brain network" including the STS region involved in processing human voices.

Quality of life and auditory performance in adults with asymmetric hearing loss.

We evaluated the relationship between binaural hearing deficits and quality of life. The study included 49 adults with asymmetric hearing loss (AHL), and 11 adult normal-hearing listeners (NHL) served as controls. Speech reception thresholds (SRT) were assessed with the French Matrix Test. Quality of life was evaluated with the Speech, Spatial and Qualities of Hearing Scale (SSQ) and the Glasgow Health Status Inventory. Speech recognition in noise was significantly poorer for AHL subjects [-0.12 dB signal-to-noise ratio (SNR) in dichotic (with speech presented to the poorer ear and noise to the better ear), -1.72 dB in diotic and -6.84 dB in reverse-dichotic conditions] compared to NHL (-4.98 dB in diotic and -9.58 dB in dichotic conditions). Scores for quality-of-life questionnaires were significantly below norms. Significant correlations were found between the SRT for the dichotic condition and the SSQ total score (r = -0.38, p = 0.01), and pure-tone average thresholds for both groups.

Brain prediction of auditory emphasis by facial expressions during audiovisual continuous speech.

The visual cues involved in auditory speech processing are not restricted to information from lip movements but also include head or chin gestures and facial expressions such as eyebrow movements. The fact that visual gestures precede the auditory signal implicates that visual information may influence the auditory activity. As visual stimuli are very close in time to the auditory information for audiovisual syllables, the cortical response to them usually overlaps with that for the auditory stimulation; the neural dynamics underlying the visual facilitation for continuous speech therefore remain unclear. In this study, we used a three-word phrase to study continuous speech processing. We presented video clips with even (without emphasis) phrases as the frequent stimuli and with one word visually emphasized by the speaker as the non-frequent stimuli. Negativity in the resulting ERPs was detected after the start of the emphasizing articulatory movements but before the auditory stimulus, a finding that was confirmed by the statistical comparisons of the audiovisual and visual stimulation. No such negativity was present in the control visual-only condition. The propagation of this negativity was observed between the visual and fronto-temporal electrodes. Thus, in continuous speech, the visual modality evokes predictive coding for the auditory speech, which is analysed by the cerebral cortex in the context of the phrase even before the arrival of the corresponding auditory signal.

Integrative activity of neural networks may code virtual spaces with internal representations.

It was shown recently in neuroimaging that spatial differentiation of brain activity provides novel information about brain function. This confirms the integrative organisation of brain activity, but given present technical limitations of neuroimaging approaches, the exact role of integrative activity remains unclear. We trained a neural network to integrate information using random numbers so as to imitate the "centre-periphery" pattern of brain activity in neuroimaging. Only the hierarchical organisation of the network permitted the learning of fast and reliable integration. We presented images to the trained network and, by spatial differentiation of the network activity, obtained virtual spaces with the presented images. Thus, our study established the necessity of the hierarchical organisation of neural networks for integration and demonstrated that the role of neural integration in the brain may be to create virtual spaces with internal representations of the objects.

Neuroenergetics at the brain-mind interface: a conceptual approach.

Modern neuroimaging techniques, such as PET and fMRI, attracted specialists in cognitive processing to the problems of brain energy and its transformations in relation to information processing. Neuroenergetics has experienced explosive progress during the last decade, complex biochemical and biophysical models of energy turnover in the brain necessitate the search of the general principles behind them, which could be linked to the cognitive view of the brain. In our conceptual descriptive generalization, we consider how the basic thermodynamical reasoning can be used to better understand brain energy. We suggest how thermodynamical principles can be applied to the existing data and theories to obtain the holistic framework of energetic processes in the brain coupled with information processing. This novel and purely descriptive framework permits the integration of approaches of different disciplines to cognitive processing: psychology, physics, physiology, mathematics, molecular biology, biochemistry, etc. Thus, the proposed general principled approach would be helpful for specialists from different fields of cognition.