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Using a set of psychophysical tests, we compared the olfactory abilities of 8 persons who became blind early in life and 16 sighted persons in a control group who were matched for age, sex, and handedness. The results indicated that those who became blind early in life developed compensatory perceptual mechanisms in the olfactory domain that involve basic sensory processes, such as the detection of odors. [ABSTRACT FROM AUTHOR]

Face perception in humans and nonhuman primates is accomplished by a patchwork of specialized cortical regions. How these regions develop has remained controversial. In sighted individuals, facial information is primarily conveyed via the visual modality. Early blind individuals, on the other hand, can recognize shapes using auditory and tactile cues. Here we demonstrate that such individuals can learn to distinguish faces from houses and other shapes by using a sensory substitution device (SSD) presenting schematic faces as sound-encoded stimuli in the auditory modality. Using functional MRI, we then asked whether a face-selective brain region like the fusiform face area (FFA) shows selectivity for faces in the same subjects, and indeed, we found evidence for preferential activation of the left FFA by sound-encoded faces. These results imply that FFA development does not depend on experience with visual faces per se but may instead depend on exposure to the geometry of facial configurations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Plaza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The present data article provides a dataset of psychological scores, additional description of used measures, and descriptive data of participants related to the research article entitled "Impact of physical exercise on depression and anxiety in adolescent inpatients: a randomized controlled trial" (Philippot et al., 2022). This randomized controlled trial aimed at assessing the effect of add-on treatment with structured physical exercise compared to social relaxation activities in a clinical population of adolescents hospitalized for depression and anxiety in a psychiatric hospital. A group of 40 adolescents was randomly assigned to either a physical exercise or a control program three to four times per week over six weeks. The primary outcome was the Hospital Anxiety Depression Scale (HADS) for evaluation of depression and anxiety symptoms. Secondary outcomes were psychological self-assessments (The Zung Self-Assessment Depression Scale (SDS), Beck's abbreviated Depression Inventory (BDI-13), The Child Depression Inventory (CDI), The State-Trait Anxiety Inventory (STAI)), diagnostic interview (Hamilton Depression Rating Scale), and physical examinations (an adapted version of the Astrand-Rhyming Sub-Maximal Effort Test and BMI measures). These questionnaires and tests were filled at baseline and after intervention., Competing Interests: AG De Volder is Senior Research Associate at the Belgian National Fund for Scientific Research. This study was supported by sponsorship of the Baillet-Latour asbl Funds (Belgium) to Prof. V. Dubois in the AREA+ hospital. The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2022 The Authors. Published by Elsevier Inc.)

Background: Physical exercise therapy is of proven efficacy in the treatment of adults with depression, but corresponding evidence is lacking in depressed adolescent inpatients. The aim of this study was to document the effect of add-on treatment with structured physical exercise in a clinical population of adolescents hospitalized for depression and anxiety in a psychiatric hospital., Methods: A group of 52 adolescent inpatients was randomly assigned to a physical exercise or control program three to four times per week over a six-week period (20 hours in total). The primary outcome was the Hospital Anxiety Depression Scale (HADS) for evaluation of depression and anxiety symptoms. Secondary outcomes were psychological self-assessments, diagnostic interviews, and physical examinations., Results: Six participants were lost in each group, leaving 20 inpatients each in the intervention and control groups. A linear mixed model with F-test revealed a significant interaction in favor of physical exercise in reducing the mean depression score (HADS-D) by 3.8 points [95% (CI), range 1.8 to 5.7], compared to a mean reduction score of 0.7 [95% (CI), range -0,7 to 2.0] in the control group. No significant interaction was found for anxiety symptoms (HADS-A)., Limitations: The investigation was limited to the six-week hospital window and the small sample size prevented exploring differences in social characteristics., Conclusion: Structured physical exercise add-on therapy integrated into the psychiatric hospitalization of adolescents has led to a reduction in their depressive symptoms, demonstrating its effectiveness in the care of adolescent inpatients with depression., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Using functional magnetic resonance imaging, here we monitored the brain activity in 12 early blind subjects and 12 blindfolded control subjects, matched for age, gender and musical experience, during a beat detection task. Subjects were required to discriminate regular ("beat") from irregular ("no beat") rhythmic sequences composed of sounds or vibrotactile stimulations. In both sensory modalities, the brain activity differences between the two groups involved heteromodal brain regions including parietal and frontal cortical areas and occipital brain areas, that were recruited in the early blind group only. Accordingly, early blindness induced brain plasticity changes in the cerebral pathways involved in rhythm perception, with a participation of the visually deprived occipital brain areas whatever the sensory modality for input. We conclude that the visually deprived cortex switches its input modality from vision to audition and vibrotactile sense to perform this temporal processing task, supporting the concept of a metamodal, multisensory organization of this cortex.

Aim: The intensity of the most appropriate exercise to use in depressed youth is unclear due to differences in methodology and the lack of evidence documenting the effect of physical activity in children. Therefore, the authors of this study attempted to document the effectiveness of different training intensities to reduce symptoms of depression and anxiety in pre-teens., Methods: The study included twenty-seven, randomly selected pre-adolescents (aged between 9-11 years of age) all of whom had Primary education. The participants were enrolled and, over a 5-week period, were subject to either intensive or low-to-moderate exercise programs four times a week. Psychological self-reports, as well as physical examinations, were conducted before and after such programs in blinded assessments. Psychological effects were considered the primary outcome, whilst physical condition was secondary., Results: Four subjects were lost and twenty-three were analyzed. General linear model with 2 criteria revealed significant changes ( p = 0.05) in trait anxiety symptoms over time in the low-to-moderate intensity group (LMIG). Within group changes followed a significant decrease in levels of anxiety (38.82 ± 2.20 to 33.36 ± 2.83, p = 0.004) and depression (10.36 ± 2.83 to 6.73 ± 1.88, p = 0.006) related symptoms amongst those in the LMIG., Interpretation: This study indicated that depression and anxiety symptoms were reduced amongst a non-clinical sample of Primary educated pre-adolescents when they were subject to a low-to-moderate exercise program. The program focused on associating movement with pleasure, encouraged positive and non-competitive interactions between participants., Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02970825, autumn 2016, updated May 7, 2018 (https://clinicaltrials.gov/ct2/show/NCT02970825).

Introduction: Since we recently showed in behavioural tasks that the top-down cognitive control was specifically altered in tinnitus sufferers, here we wanted to establish the link between this impaired executive function and brain alterations in the frontal cortex in tinnitus patients., Method: Using functional magnetic resonance imaging (fMRI), we monitored the brain activity changes in sixteen tinnitus patients (TP) and their control subjects (CS) while they were performing a spatial Stroop task, both in audition and vision., Results: We observed that TP differed from CS in their functional recruitment of the dorsolateral prefrontal cortex (dlPFC, BA46), the cingulate gyrus and the ventromedial prefrontal cortex (vmPFC, BA10). This recruitment was higher during interference conditions in tinnitus participants than in controls, whatever the sensory modality. Furthermore, the brain activity level in the right dlPFC and vmPFC correlated with the performance in the Stroop task in TP., Conclusion: Due to the direct link between poor executive functions and prefrontal cortex alterations in TP, we postulate that a lack of inhibitory modulation following an impaired top-down cognitive control may maintain tinnitus by hampering habituation mechanisms. This deficit in executive functions caused by prefrontal cortex alterations would be a key-factor in the generation and persistence of tinnitus.

Hearing a beat recruits a wide neural network that involves the auditory cortex and motor planning regions. Perceiving a beat can potentially be achieved via vision or even touch, but it is currently not clear whether a common neural network underlies beat processing. Here, we used functional magnetic resonance imaging (fMRI) to test to what extent the neural network involved in beat processing is supramodal, that is, is the same in the different sensory modalities. Brain activity changes in 27 healthy volunteers were monitored while they were attending to the same rhythmic sequences (with and without a beat) in audition, vision and the vibrotactile modality. We found a common neural network for beat detection in the three modalities that involved parts of the auditory dorsal pathway. Within this network, only the putamen and the supplementary motor area (SMA) showed specificity to the beat, while the brain activity in the putamen covariated with the beat detection speed. These results highlighted the implication of the auditory dorsal stream in beat detection, confirmed the important role played by the putamen in beat detection and indicated that the neural network for beat detection is mostly supramodal. This constitutes a new example of convergence of the same functional attributes into one centralized representation in the brain., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented "visual" cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here.

Early blindness results in both structural and functional changes of the brain. However, these changes have rarely been studied in relation to each other. We measured alterations in cortical thickness (CT) caused by early visual deprivation and their relationship with cortical activity. Structural and functional magnetic resonance imaging was performed in 12 early blind (EB) humans and 12 sighted controls (SC). Experimental conditions included one-back tasks for auditory localization and pitch identification, and a simple sound-detection task. Structural and functional data were analyzed in a whole-brain approach and within anatomically defined regions of interest in sensory areas of the spared (auditory) and deprived (visual) modalities. Functional activation during sound-localization or pitch-identification tasks correlated negatively with CT in occipital areas of EB (calcarine sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus) and in nonprimary auditory areas of SC. These results suggest a link between CT and activation and demonstrate that the relationship between cortical structure and function may depend on early sensory experience, probably via selective pruning of exuberant connections. Activity-dependent effects of early sensory deprivation and long-term practice are superimposed on normal maturation and aging. Together these processes shape the relationship between brain structure and function over the lifespan., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Tinnitus is the perception of sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. In experiment 1, we used a go/no-go paradigm to evaluate the target detection speed and the inhibitory control in tinnitus participants (TP) and control subjects (CS), both in unimodal and bimodal conditions in the auditory and visual modalities. We also tested whether the sound frequency used for target and distractors affected the performance. We observed that TP were slower and made more false alarms than CS in all unimodal auditory conditions. TP were also slower than CS in the bimodal conditions. In addition, when comparing the response times in bimodal and auditory unimodal conditions, the expected gain in bimodal conditions was present in CS, but not in TP when tinnitus-matched frequency sounds were used as targets. In experiment 2, we tested the sensitivity to cross-modal interference in TP during auditory and visual go/no-go tasks where each stimulus was preceded by an irrelevant pre-stimulus in the untested modality (e.g. high frequency auditory pre-stimulus in visual no/no-go condition). We observed that TP had longer response times than CS and made more false alarms in all conditions. In addition, the highest false alarm rate occurred in TP when tinnitus-matched/high frequency sounds were used as pre-stimulus. We conclude that the inhibitory control is altered in TP and that TP are abnormally sensitive to cross-modal interference, reflecting difficulties to ignore irrelevant stimuli. The fact that the strongest interference effect was caused by tinnitus-like auditory stimulation is consistent with the hypothesis according to which such stimulations generate emotional responses that affect cognitive processing in TP. We postulate that executive functions deficits play a key-role in the perception and maintenance of tinnitus.

Purpose: Tinnitus is the perception of a sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. Here, we hypothesize that these brain alterations affect top-down cognitive control mechanisms that play a role in the regulation of sensations, emotions and attention resources., Methods: The efficiency of the executive control as well as simple reaction speed and processing speed were evaluated in tinnitus participants (TP) and matched control subjects (CS) in both the auditory and the visual modalities using a spatial Stroop paradigm., Results: TP were slower and less accurate than CS during both the auditory and the visual spatial Stroop tasks, while simple reaction speed and stimulus processing speed were affected in TP in the auditory modality only., Conclusions: Tinnitus is associated both with modality-specific deficits along the auditory processing system and an impairment of cognitive control mechanisms that are involved both in vision and audition (i.e. that are supra-modal). We postulate that this deficit in the top-down cognitive control is a key-factor in the development and maintenance of tinnitus and may also explain some of the cognitive difficulties reported by tinnitus sufferers.

The "neural Darwinism" theory predicts that when one sensory modality is lacking, as in congenital blindness, the target structures are taken over by the afferent inputs from other senses that will promote and control their functional maturation (Edelman, 1993). This view receives support from both cross-modal plasticity experiments in animal models and functional imaging studies in man, which are presented here., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Although early blind (EB) individuals are thought to have a better musical sense than sighted subjects, no study has investigated the musical rhythm and beat processing abilities in EB individuals. Using an adaptive 'up and down' procedure, we measured the beat asynchrony detection threshold and the duration discrimination threshold, in the auditory and vibrotactile modalities in both EB and sighted control (SC) subjects matched for age, gender, and musical experience. We observed that EB subjects were better than SC in the beat asynchrony detection task; that is, they showed lower thresholds than SC, both in the auditory and in the vibrotactile modalities. In addition, EB subjects had a lower threshold than SC for duration discrimination in the vibrotactile modality only. These improved beat asynchrony detection abilities may contribute to the known excellent musical abilities often observed in many blind subjects.

In number comparison tasks, the performance is better when the distance between the numbers to compare increases. It has been shown that this so-called numerical distance effect (NDE) decreases with age but the neuroanatomical correlates of these age-related changes are poorly known. Using functional magnetic resonance imaging (fMRI), we recorded the brain activity changes in children aged from 8 to 14 years while they performed a number comparison task on pairs of Arabic digits and a control color comparison task on non-numerical symbols. On the one hand, we observed developmental changes in the recruitment of frontal regions and the left intraparietal sulcus (IPS), with lower activation as age increased. On the other hand, we found that a behavioral index of selective sensitivity to the NDE was positively correlated with higher brain activity in a right lateralized occipito-temporo-parietal network including the IPS. This leads us to propose that the left IPS would be engaged in the refinement of cognitive processes involved in number comparison during development, while the right IPS would underlie the semantic representation of numbers and its activation would be mainly affected by the numerical proximity between them.

Using functional magnetic resonance imaging (fMRI) in ten early blind humans, we found robust occipital activation during two odor-processing tasks (discrimination or categorization of fruit and flower odors), as well as during control auditory-verbal conditions (discrimination or categorization of fruit and flower names). We also found evidence for reorganization and specialization of the ventral part of the occipital cortex, with dissociation according to stimulus modality: the right fusiform gyrus was most activated during olfactory conditions while part of the left ventral lateral occipital complex showed a preference for auditory-verbal processing. Only little occipital activation was found in sighted subjects, but the same right-olfactory/left-auditory-verbal hemispheric lateralization was found overall in their brain. This difference between the groups was mirrored by superior performance of the blind in various odor-processing tasks. Moreover, the level of right fusiform gyrus activation during the olfactory conditions was highly correlated with individual scores in a variety of odor recognition tests, indicating that the additional occipital activation may play a functional role in odor processing.

While the effects of early visual deprivation on auditory and tactile functions have been widely studied, little is known about olfactory function in early blind subjects. The present study investigated the potential effect of early blindness on the electrophysiological correlates of passive odour perception. Event-related potentials (ERPs) were recorded in eight early blind humans and eight sighted controls matched for age, sex and handedness during olfactory stimulation with 2-phenyl ethyl alcohol and trigeminal stimulation with CO2 Latencies, amplitudes and topographical distributions were analysed. As expected, the olfactory and trigeminal ERP components showed normal latencies, amplitudes and topography in both groups. Olfactory stimuli generated responses of smaller amplitude than those observed in response to trigeminal stimulation. In addition, ERP analyses did not reveal any major difference in electrocortical responses in occipital areas in early blind and sighted subjects. These results suggest that passive olfactory and trigeminal stimulation elicit the same electrophysiological responses in both groups, confirming that the neurophysiological correlates of the cross-modal compensatory mechanisms in early blind subjects do not appear during passive olfactory and trigeminal perception.

It has been shown that the volume of the olfactory bulb (OB) changes with function. The aim of this study was to investigate whether the OB volume and the olfactory function in early blind (EB) subjects increase compared with controls. Psychophysical testing of olfactory performances and OB volumetric measurements assessed by an MRI scan were studied. Quantitative olfactory function expressed in the odor discrimination and odor-free identification scores was higher in EB subjects compared with controls. The mean of right, left and total OB volume was 65.40, 75.48, and 140.89 mm, respectively for the EB subjects and 54.47, 52.11, and 106.60 mm, respectively for the controls, with these differences being significant. EB subjects have superior olfactory abilities and presented with significantly higher OB volume than the sighted controls. OB plasticity may explain this compensatory mechanism between visual deprivation and enhanced olfactory perception.

We describe the development and evaluation of a computer-controlled system for delivering odors in a magnetic resonance imaging (MRI) environment. The system allows a timely presentation of different odors in synchrony with MRI sequences and participant's inspiration phase. The rise/fall time of odor deliverance has been optimized to generate prompt and strong stimulations. Equipped with a user-friendly programming interface, the system can be used reliably in a wide range of experimental paradigms. We have paid particular attention to developing a portable system that is relatively easy, rapid, and inexpensive to replicate. The equipment has been tested in a 3-Tesla MRI in a boxcar paradigm, in which stimulation conditions alternated with rest periods (no stimulation). The experiment demonstrated the good functioning of the device and its efficiency in producing the expected activation in the olfactory cortex; it also revealed some methodological and technical aspects to be improved.

The occipital cortex (OC) of early-blind humans is activated during various nonvisual perceptual and cognitive tasks, but little is known about its modular organization. Using functional MRI we tested whether processing of auditory versus tactile and spatial versus nonspatial information was dissociated in the OC of the early blind. No modality-specific OC activation was observed. However, the right middle occipital gyrus (MOG) showed a preference for spatial over nonspatial processing of both auditory and tactile stimuli. Furthermore, MOG activity was correlated with accuracy of individual sound localization performance. In sighted controls, most of extrastriate OC, including the MOG, was deactivated during auditory and tactile conditions, but the right MOG was more activated during spatial than nonspatial visual tasks. Thus, although the sensory modalities driving the neurons in the reorganized OC of blind individuals are altered, the functional specialization of extrastriate cortex is retained regardless of visual experience., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Aim: Sensory substitution (SS) represents a unique opportunity to provide congenitally blind persons with visual-like experience. Although visual experience influences the way we perceive the external world, little is known about the effects of SS experience., Purpose: To investigate the effects of perceptual experience (visual versus sensory substitution) on depth perception through an SS system, object localization abilities of early blind (n = 10), and blindfolded sighted control subjects (n = 20) were assessed before and after a practicing period with a visual-to-auditory SS device., Method: During the pre- and post-test, subjects had to replace, by hand, an object previously localized using the device. The practicing phase consisted of three sessions during which subjects tried to localize and grasp an object using the device. Results. At the pre-test, sighted subjects spontaneously used efficiently different pictorial depth cues to estimate object distance while the blind subjects were affected by their lack of visual experience and were significantly less accurate. Post-test showed that the brief practicing phase sufficed to enable blind subjects to acquire the rules of visual depth and to use them efficiently with the device., Conclusions: These results suggest the possibility to compensate for some effects of early and long-lasting blindness by providing visual-like experience via SS. Theoretical implications are discussed.

Previous studies showed that early blind humans develop superior abilities in the use of their remaining senses, hypothetically due to a functional reorganization of the deprived visual brain areas. While auditory and tactile functions have been investigated for long, little is known about the effects of early visual deprivation on olfactory processing. However, blind humans make an extensive use of olfactory information in their daily life. Here we investigated olfactory discrimination and identification abilities in early blind subjects and age-matched sighted controls. Three levels of cuing were used in the identification task, i.e., free-identification (no cue), categorization (semantic cues) and multiple choice (semantic and phonological cues). Early blind subjects significantly outperformed the controls in odour discrimination, free-identification and categorization. In addition, the larger group difference was observed in the free-identification as compared to the categorization and the multiple choice conditions. This indicated that a better access to the semantic information from odour perception accounted for part of the improved olfactory performances in odour identification in the blind. We concluded that early blind subjects have both improved perceptual abilities and a better access to the information stored in semantic memory than sighted subjects.

Congenital blindness is one of the rare human models to explore the role of experience-driven cross-modal compensation after early sensory deprivation. We re-examined spatial attention abilities in congenitally blind participants and sighted controls using a paradigm comparable to the one of our previous study (Collignon, Renier, Bruyer, Tranduy, & Veraart, 2006), except that this time the auditory and tactile stimuli were now presented in sequence. Although both groups performed the task with similar accuracy, we observed that blind participants had shorter reaction times than sighted controls for the detection of spatial targets in both sensory modalities. Moreover, this finding held true for both the selective and divided attention conditions. These results not only confirm previous reports on the superiority of the blind during auditory and tactile attention tasks, but also broaden our knowledge of the mechanisms underlying cross-modal compensation., ((c) 2009 APA, all rights reserved.)

The segregation between cortical pathways for the identification and localization of objects is thought of as a general organizational principle in the brain. Yet, little is known about the unimodal versus multimodal nature of these processing streams. The main purpose of the present study was to test whether the auditory and tactile dual pathways converged into specialized multisensory brain areas. We used functional magnetic resonance imaging (fMRI) to compare directly in the same subjects the brain activation related to localization and identification of comparable auditory and vibrotactile stimuli. Results indicate that the right inferior frontal gyrus (IFG) and both left and right insula were more activated during identification conditions than during localization in both touch and audition. The reverse dissociation was found for the left and right inferior parietal lobules (IPL), the left superior parietal lobule (SPL) and the right precuneus-SPL, which were all more activated during localization conditions in the two modalities. We propose that specialized areas in the right IFG and the left and right insula are multisensory operators for the processing of stimulus identity whereas parts of the left and right IPL and SPL are specialized for the processing of spatial attributes independently of sensory modality.

It is well known that, following an early visual deprivation, the neural network involved in processing auditory spatial information undergoes a profound reorganization. In particular, several studies have demonstrated an extensive activation of occipital brain areas, usually regarded as essentially "visual", when early blind subjects (EB) performed a task that requires spatial processing of sounds. However, little is known about the possible consequences of the activation of occipitals area on the function of the large cortical network known, in sighted subjects, to be involved in the processing of auditory spatial information. To address this issue, we used event-related transcranial magnetic stimulation (TMS) to induce virtual lesions of either the right intra-parietal sulcus (rIPS) or the right dorsal extrastriate occipital cortex (rOC) at different delays in EB subjects performing a sound lateralization task. Surprisingly, TMS applied over rIPS, a region critically involved in the spatial processing of sound in sighted subjects, had no influence on the task performance in EB. In contrast, TMS applied over rOC 50 ms after sound onset, disrupted the spatial processing of sounds originating from the contralateral hemifield. The present study shed new lights on the reorganisation of the cortical network dedicated to the spatial processing of sounds in EB by showing an early contribution of rOC and a lesser involvement of rIPS.

It has been suggested that both the posterior parietal cortex (PPC) and the extrastriate occipital cortex (OC) participate in the spatial processing of sounds. However, the precise time-course of their contribution remains unknown, which is of particular interest, considering that it could give new insights into the mechanisms underlying auditory space perception. To address this issue, we have used event-related transcranial magnetic stimulation (TMS) to induce virtual lesions of either the right PPC or right OC at different delays in subjects performing a sound lateralization task. Our results confirmed that these two areas participate in the spatial processing of sounds. More precisely, we found that TMS applied over the right OC 50 msec after the stimulus onset significantly impaired the localization of sounds presented either to the right or to the left side. Moreover, right PPC virtual lesions induced 100 and 150 msec after sound presentation led to a rightward bias for stimuli delivered on the center and on the left side, reproducing transiently the deficits commonly observed in hemineglect patients. The finding that the right OC is involved in sound processing before the right PPC suggests that the OC exerts a feedforward influence on the PPC during auditory spatial processing.

A major question in the field of sensory substitution concerns the nature of the perception generated by sensory substitution prostheses. Is the perception determined by the nature of the substitutive modality or is it determined by the nature of the information transmitted by the device? Is it a totally new, amodal, perception? This paper reviews the recent neuroimaging studies which have investigated the neural bases of sensory substitution. The detailed analysis of available results led us to propose a general scheme of the neural mechanisms underlying sensory substitution. Two different main processes may be responsible for the visual area recruitment observed in the different studies: cross-modality and mental (visual) imagery. Based on our results analysis, we propose that cross-modality is the predominant process in early blind subjects whereas mental imagery is predominant in blindfolded sighted subjects. This model implies that, with training, sensory substitution mainly induces visual-like perception in sighted subjects and mainly auditory or tactile perception in blind subjects. This framework leads us to make some predictions that could easily be tested.

We have previously shown that some visual motion areas can be specifically recruited by auditory motion processing in blindfolded sighted subjects [Poirier, C., Collignon, O., De Volder, A.G., Renier, L., Vanlierde, A., Tranduy, D., Scheiber, C., 2005. Specific activation of V5 brain area by auditory motion processing: an fMRI study. Brain Res. Cogn. Brain Res. 25, 650-658]. The present fMRI study investigated whether auditory motion processing may recruit the same brain areas in early blind subjects. The task consisted of simultaneously determining both the nature of a sound stimulus (pure tone or complex sound) and the presence or absence of its movement. When a movement was present, blind subjects had to identify its direction. Auditory motion processing, as compared to static sound processing, activated the brain network of auditory and visual motion processing classically observed in sighted subjects. Accordingly, brain areas previously considered as specific to visual motion processing could be specifically recruited in blind people by motion stimuli presented through the auditory modality. This indicates that the occipital cortex of blind people could be organized in a modular way, as in sighted people. The similarity of these results with those we previously observed in sighted subjects suggests that occipital recruitment in blind people could be mediated by the same anatomical connections as in sighted subjects.

This experiment was undertaken to investigate the effect of sensory modality (vision vs. audition) and of visual status (early blind vs. sighted) on susceptibility to the vertical-horizontal illusion. Early blind volunteers and blindfolded sighted subjects explored variants of the vertical-horizontal illusion using a device that substituted audition for vision, whereas sighted subjects from an independent group inspected the same stimuli visually. Sensitivity to the vertical-horizontal illusion, including an illusion of moderate strength when using the sensory substitution device, was observed only in the two sighted groups. The existence of an illusion effect when using such a device supports the idea of a visual perception provided by sensory substitution, whereas the attenuation of the vertical-horizontal illusion strength is consistent with the visual field shape theory (Künnapas, 1955a). The absence of the illusion effect in early blind subjects suggests that the sensory experience influences the nature of perception and that the visual experience plays a crucial role in the vertical-horizontal illusion, in accordance with the size-constancy scaling theory (Gregory, 1963).

The learning process related to pattern and object recognition is difficult to study because the human brain has a remarkable capacity to recognise complex visual forms from early infancy. In the present study, we investigated on-going neural changes underlying the learning process of visual pattern recognition by means of a device substituting audition for vision. Functional MRI evidenced the gradual pattern recognition-induced recruitment of the ventral visual stream, bilaterally, from learning session 1 to session 3, and a slight decrease in these activation foci from session 3 to session 4. The initial increase in activation is thought to reflect the gradually enhanced visualisation of patterns in the subjects' mind across sessions. By contrast the subsequent decrease reported at the end of the training period is interpreted as the progressive optimisation of neuronal responses elicited by the task. Our results, in accordance with previous observations, suggest that the succession of activation increase and decrease in sensori-motor areas could be a general rule in sensory and sensori-motor learning.

Sensory substitution refers to the use of one sense to pick up information normally gathered by another sensory organ. With recent technological advances and scientific progress, sensory substitution appears as an interesting alternative for restoring some functions of a defective sensory organ (e.g., the sight in case of blindness). At the same time, our knowledge about cognitive and brain mechanisms involved in sensory substitution has grown considerably, bringing new insights into human perception and neural plasticity. From this perspective, sensory substitution can be considered as both a tool to investigate human cognition and brain functions, and a research topic in its own right. This paper addresses some of the major questions raised by sensory substitution, demonstrates how the study of sensory substitution enhances our understanding of human perception and brain plasticity and provides an overview of rehabilitation potentialities.

Previous neuroimaging studies identified multimodal brain areas in the visual cortex that are specialized for processing specific information, such as visual-haptic object recognition. Here, we test whether visual brain areas are involved in depth perception when auditory substitution of vision is used. Nine sighted volunteers were trained blindfolded to use a prosthesis substituting vision with audition both to recognize two-dimensional figures and to estimate distance of an object in a real three-dimensional environment. Using positron emission tomography, regional cerebral blood flow was assessed while the prosthesis was used to explore virtual 3D images; subjects focused either on 2D features (target search) or on depth (target distance comparison). Activation foci were found in visual association areas during both the target search task, which recruited the occipito-parietal cortex, and the depth perception task, which recruited occipito-parietal and occipito-temporal areas. This indicates that some brain areas of the visual cortex are relatively multimodal and may be recruited for depth processing via a sense other than vision.

We tested the effects of using a prosthesis for substitution of vision with audition (PSVA) on sensitivity to the Ponzo illusion. The effects of visual experience on the susceptibility to this illusion were also assessed. In one experiment, both early-blind and blindfolded sighted volunteers used the PSVA to explore several variants of the Ponzo illusion as well as control stimuli. No effects of the illusion were observed. The results indicate that subjects focused their attention on the two central horizontal bars of the stimuli, without processing the contextual cues that convey perspective in the Ponzo figure. In a second experiment, we required subjects to use the PSVA to consider the two converging oblique lines of the stimuli before comparing the length of the two horizontal bars. Here we were able to observe susceptibility to the Ponzo illusion in the sighted group, but to a lesser extent than in a sighted non-PSVA control group. No clear effect of the ilusion was obtained in early-blind subjects. These results suggest that, at least in sighted subjects, perception obtained with the PSVA shares perceptual processes with vision. Visual experience appears mandatory for a Ponzo illusion to occur with the PSVA.

Using functional magnetic resonance imaging, the brain activation related to unilateral sequential finger-to-thumb opposition was studied in six children with a right congenital hemiplegia of cortical origin. They were compared to six age-matched controls. In the control group, movements with either hand asymmetrically activated the sensorimotor cortex and premotor areas in both cerebral hemispheres with a typical contralateral predominance. By contrast, paretic finger movements activated both hemispheres in the hemiplegic patients, with a strong ipsilateral predominance favoring the undamaged hemisphere. The activation induced by nonparetic finger movements was restricted to the contralateral undamaged hemisphere. Furthermore, the level of activation in the undamaged cortex was partly related to residual finger dexterity, according to covariance analysis. These activation patterns indicate an adaptive reorganization of the cortical motor networks in this group of patients, with a prominent involvement of the undamaged hemisphere in the control of finger movements with either hand.

Using positron emission tomography, regional cerebral blood flow was studied in five early blind and five control volunteers during visuo-spatial imagery. Subjects were instructed to generate a mental representation of verbally provided bidimensional patterns that were placed in a grid and to assess pattern symmetry in relation to a grid axis. This condition was contrasted with a verbal memory task. Cerebral activation in both groups was similar during the visuo-spatial imagery task. It involved the precuneus (BA 7), superior parietal lobule (BA 7), and occipital gyrus (BA 19). These results are in accordance with previous studies conducted in sighted subjects that indicated that the same occipito-parietal areas are involved in visual perception as well as in mental imagery dealing with spatial components. The dorsal pathway seems to be involved in visuo-spatial imagery in early blind subjects, indicating that this pathway undergoes development in the absence of vision.

Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

The resting brain metabolism was estimated in six children suffering from a right congenital hemiplegia (CH) of subcortical origin. This estimate was based on the 18F-labeled 2-deoxy-2-fluoro-d-glucose (FDG) uptake measured by means of positron emission tomography and compared, using statistical parametric mapping (SPM99), with that of six control subjects. The contrast [CH children - Controls] showed that CH children had two loci of relatively higher FDG uptake. The larger voxel cluster was found in the ipsilesional hemisphere and comprised the primary motor and somatosensory cortices and left inferior parietal lobule. The other cluster was located in the contralesional hemisphere and encompassed the primary motor cortex, callosomarginal sulcus, and cingulate gyrus. The reverse contrast [Controls - CH children] showed that control subjects had a relatively higher FDG uptake bilaterally in the temporal and hippocampal gyri, the rostral part of the brain stem, the thalami, the putamen, and the superior frontal gyri. A crossed cerebellar diaschisis was not observed in CH children. This relatively higher FDG uptake in the ipsi- and contralesional motor areas of CH children stands out in contrast to the hypometabolism (diaschisis) frequently observed in adult stroke patients with a subcortical lesion. This increased FDG uptake in the disconnected ipsilesional motor areas may reflect a long-term adaptation leading, for example, to an increased synaptic density and/or activity or to a change in the density of glucose transporters., ((C)2002 Elsevier Science (USA).)

Hypothyroidism is often associated with defective memory, psychomotor slowing, and depression. However, the relationship between thyroid status and cognitive or psychiatric disturbances remains unclear. Using psychometric scales, 10 patients who had undergone total thyroidectomy for thyroid carcinoma were evaluated for depression, anxiety, and psychomotor slowing; they were examined both when euthyroid and hypothyroid after thyroid hormone withdrawal. Positron emission tomography was used, with oxygen-15-labeled water and fluorine-18F-labeled 2-deoxy-2fluoro-D-glucose as the tracers, to correlate the regional cerebral blood flow and cerebral glucose metabolism with the mental state in patients. Two different image analysis techniques (regions of interest and statistical parametric maps) were applied. In hypothyroidism, there was a generalized decrease in regional cerebral blood flow (23.4%, P < 0.001) and in cerebral glucose metabolism (12.1%, P < 0.001) and there were no specific local defects. Patients were also significantly more depressed (P < 0.001), anxious (P < 0.001) and psychomotor slowed (P < 0.005) in hypo than in euthyroid status. These results indicate that the brain activity was globally reduced in severe hypothyroidism of short duration without the regional modifications usually observed in primary depression.

Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision.

This PET study aimed at investigating the neural structures involved in pattern recognition in early blind subjects using sensory substitution equipment (SSE). Six early blind and six blindfolded sighted subjects were studied during three auditory processing tasks: a detection task with noise stimuli, a detection task with familiar sounds, and a pattern recognition task using the SSE. The results showed a differential activation pattern with the SSE as a function of the visual experience: in addition to the regions involved in the recognition process in sighted control subjects, occipital areas of early blind subjects were also activated. The occipital activation was more important when the early blind subjects used SSE than during the other auditory tasks. These results suggest that activity of the extrastriate visual cortex of early blind subjects can be modulated and bring additional evidence that early visual deprivation leads to cross-modal cerebral reorganization., (Copyright 2001 Academic Press.)

As a first approach to study the effect of early visual deprivation in the GABA-ergic inhibitory system, the distribution of benzodiazepine receptors (BZR) was accurately estimated using [11C]flumazenil ([11C]FMZ). Measurements were carried out in five subjects who became blind early in life and in five sighted control subjects. The interactions between [11C]FMZ and BZR were described using a non-linear compartmental analysis which permitted to estimate the BZR synaptic density independently of other model parameters. The distribution of BZR in the visual areas and other cortical regions of blind subjects was qualitatively and quantitatively similar to that of controls. However, the BZR density in the cerebellum was significantly lower in blind than in control subjects (P<0.01). Our findings suggest that modifications of the cerebellar neural circuitry may be concomitant to the already observed compensatory reorganization in cerebral areas of blind subjects.

The regional cerebral blood flow (rCBF) and metabolic rate for glucose (rCMRGlc) are associated with functional activity of the neural cells. The present work reports a comparison study between rCBF and rCMRGlc in a normal population as a function of age. 10 young (25.9+/-5.6 years) and 10 old (65.4+/-6.1 years) volunteers were similarly studied at rest. In each subject, rCBF and rCMRGlc were measured in sequence, during the same session. Both rCBF and rCMRGlc values were found to decrease from young (mean rCBF=43.7 ml/100 g per min; mean rCMRGlc=40.6 micromol/100 g per min) to old age (mean rCBF=37.3 ml/100 g per min; mean rCMRGlc=35.2 micromol/100 g per min), resulting in a drop over 40 years of 14.8% (0.37%/year) and 13.3% (0.34%/year), respectively. On a regional basis, the frontal and the visual cortices were observed to have, respectively, the highest and the lowest reduction in rCBF, while, for rCMRGlc, these extremes were observed in striatum and cerebellum. Despite these differences, the ratio of rCBF to rCMRGlc was found to have a similar behavior in all brain regions for young and old subjects as shown by a correlation coefficient of 88%. This comparative study indicates a decline in rCBF and rCMRGlc values and a coupling between CBF and CMRGlc as a function of age.

In this work, a mathematical correction for metabolites has been validated which estimates the relative amount of [11C]flumazenil ([11C]FMZ) in the total plasma curve from the tissue kinetic data without the need for direct metabolite measurement in blood plasma samples. Kinetic data were obtained using a 90-min three-injection protocol on five normal volunteers. First, the relative amount of [11C]FMZ in plasma was modelled by a two-parameter exponential function. The parameters were estimated either directly by fitting this model to the blood plasma metabolite measurements, or indirectly from the simultaneous fitting of tissue time activity curves from several brain regions with a non-linear FMZ kinetic model. Second, the direct and indirect metabolite corrections were fixed and the FMZ compartmental parameters were determined on a regional basis in the brain. The validation was performed by comparing the regional values of benzodiazepine receptor density Bmax and equilibrium dissociation constant Kd obtained with the direct metabolite correction with those values obtained with the indirect correction. For Bmax, the correlation coefficient r2 was above 0.97 for all subjects and the slope values of the linear regression were within the interval [0.97, 1.2]. For Kd, r2 was above 0.96, and the slope values of the linear regression were within the interval [0.99, 1.1]. Simulation studies were performed in order to evaluate whether this metabolite correction method could be used in a clinical protocol where only a single [11C]FMZ injection and a linear compartmental model are used. The resulting [11C]FMZ distribution volume estimates were found to be linearly correlated with the true values, with r2=1.0 and a slope value of 1.1. The mathematical metabolite correction proved to be a feasible and reliable method to estimate the relative amount of [11C]FMZ in plasma and the compartmental model parameters for three-injection protocols. Although validation with real data is necessary, simulation results suggest that our analysis method may also be applied to single-injection protocols.

Quantitative estimation of brain glucose metabolism (rCMRGlc) with positron emission tomography and fluorodeoxyglucose involves arterial blood sampling to estimate the delivery of radioactivity to the brain. Usually, for an intravenous injection of 30 s duration, an accurate input curve requires a frequency of one sample every 5 s or less to determine the peak activity in arterial plasma during the first 2 min after injection. In this work, 13 standardized sampling times were shown to be sufficient to accurately define the input curve. This standardized input curve was subsequently fitted by a polynomial function for its rising part and by spectral analysis for its decreasing part. Using the measured, the standardized, and the fitted input curves, rCMRGlc was estimated in 32 cerebral regions of interest in 20 normal volunteers. Comparison of rCMRGlc values obtained with the measured and the fitted input curves showed that both procedures gave consistent results, with a maximal relative error in mean rCMRGlc of 1% when using the autoradiographic method and 2% using kinetic analysis of dynamic data. This input-curve-fitting technique, which is not dependent on the peak time occurrence, allows an accurate determination of the input-curve shape from reduced sampling schemes.

The purpose of this study was to investigate the neural networks involved when using an ultrasonic echolocation device, which is a substitution prosthesis for blindness through audition. Using positron emission tomography with fluorodeoxyglucose, regional brain glucose metabolism was measured in the occipital cortex of early blind subjects and blindfolded controls who were trained to use this prosthesis. All subjects were studied under two different activation conditions: (i) during an auditory control task, (ii) using the ultrasonic echolocation device in a spatial distance and direction evaluation task. Results showed that the abnormally high metabolism already observed in early blind occipital cortex at rest [C. Veraart, A.G. De Volder, M.C. Wanet-Defalque, A. Bol, C. Michel, A.M. Goffinet, Glucose utilization in human visual cortex is, respectively elevated and decreased in early versus late blindness, Brain Res. 510 (1990) 115-121.] was also present during the control task and showed a trend to further increase during the use of the ultrasonic echolocation device. This specific difference in occipital cortex activity between the two tasks was not observed in control subjects. The metabolic recruitment of the occipital cortex in early blind subjects using a substitution prosthesis could reflect a concurrent stimulation of functional cross-modal sensory connections. Given the unfamiliarity of the task, it could be interpreted as a prolonged plasticity in the occipital cortex early deprived of visual afferences., (Copyright 1999 Elsevier Science B.V.)

During the first years of life, the human brain undergoes repetitive modifications in its anatomical, functional, and synaptic construction to reach the complex functional organization of the adult central nervous system. As an attempt to gain further insight in those maturation processes, the evolution of cerebral metabolic activity was investigated as a function of age in epileptic infants, children and adolescents. The regional cerebral metabolic rates for glucose (rCMRGlc) were measured with positron emission tomography (PET) in 60 patients aged from 6 weeks to 19 years, who were affected by complex partial epilepsy. They were scanned at rest, without premedication, in similar conditions to 20 epileptic adults and in 49 adult controls. The distribution of brain metabolic activity successively extended from sensorimotor areas and thalamus in epileptic newborns to temporo-parietal and frontal cortices and reached the adult pattern after 1 year of age. The measured rCMRGlc in the cerebral cortex, excluding the epileptic lesions, increased from low values in infants to a maximum between 4 and 12 years, before it declined to stabilize at the end of the second decade of life. Similar age-related changes in glucose metabolic rates were not observed in the adult groups. Despite the use of medications, the observed variations of rCMRGlc with age in young epileptic humans confirm those previously described in pediatric subjects. These metabolic changes are in full agreement with the current knowledge of the synaptic density evolution in the human brain.

As an attempt to better understand the metabolic basis for the previously reported increases in glucose metabolism in the visual cortex of congenitally blind subjects, cerebral blood flow, oxygen consumption and glucose utilization were investigated with multitracer positron emission tomography. Measurements were carried out in three subjects who became blind early in life and in three age-matched blindfolded controls. Regional analysis of cerebral blood flow, metabolic rates for oxygen and glucose utilization revealed that these parameters were relatively higher in the visual cortex in case of early blindness (109.7 +/- 2.4%; 114.3 +/- 1.5%; 118.0 +/- 5.5%, respectively) than in controls (98.1 +/- 3.9%; 108.6 +/- 3.6%; 105.2 +/- 4.8%). There were slight differences, albeit statistically not significant, between early blind and control subjects in terms of oxygen-to-glucose metabolic ratios. The relatively preserved stoichiometry in the visual areas of blind subjects points to the lack of variation in the yield of glucose oxidation in this cortex. Those observations suggest that the high level of energy metabolism disclosed in early blind visual cortex is related to neural activity.

Regional brain glucose utilization was investigated with positron emission tomography and fluorodeoxyglucose in 2 patients with a seizure disorder associated with diffuse band heterotopia, a condition known as "double cortex." Although 1 patient was examined shortly after the onset of the first seizures, the other had a long history of intractable epilepsy before examination. Magnetic resonance imaging revealed a symmetric and generalized band of ectopic gray matter and an overlying normal-looking cortex, without focal abnormality. Metabolic studies yielded comparable results in both patients, with similar and even higher glucose uptake in the layer of gray matter heterotopia compared to the normal cortex. These data suggest the persistence of some synaptic activity in the heterotopic neurons, which seems unaffected by age or by the time-course of epilepsy.

Regional brain glucose utilisation was investigated with PET and fluorodeoxyglucose (FDG) in a case of epileptic aphasia (Landau-Kleffner syndrome) associated with a left sylvian arachnoid cyst. CT and MRI had failed to disclose any mass effect of the cyst on surrounding brain structures. Sequential metabolic measurements showed a comparable pronounced hypometabolism in cortical regions around the cyst, involving speech areas, and suggested mild but chronic compression of the developing brain. After placement of a cyst-peritoneal shunt system, significant metabolic improvement occurred in all cortical regions, especially the inferior frontal gyrus and the perisylvian area, with predominant residual deficit in the left superior temporal gyrus. These findings were correlated with a pronounced increase in word fluency and slower progress in verbal auditory comprehension. This report suggests that PET is able to evaluate the functional disturbances associated with expanding arachnoid cysts, and to follow the neurological improvement after drainage.

Using positron emission tomography (PET), thirteen studies of regional brain glucose utilization were performed in 12 patients with postanoxic syndrome due to cardiac arrest. Investigations were carried out at least one month after brain anoxia. Seven subjects were in a persistent vegetative state. The others had regained normal consciousness with various residual neurological signs. When compared with normal values obtained in 16 normal, age-matched subjects, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative cases, and to a lesser degree (+/- 25%) in conscious subjects. The most consistent regional alterations were observed in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories. Other selective anomalies were found in the frontomesial junction (5 cases), the striatum (3 cases with dystonia), and the visual cortex (2 cases with cortical blindness). This study suggests that cerebral anoxia results in a global brain hypometabolism, which appears related to the vigilance state, as well as in regional disturbances preferentially located in arterial border zones. Although our findings remain to be confirmed in larger series, they suggest that PET provides a useful index of residual brain tissue function after anoxia and may assist in the monitoring of postanoxic encephalopathies.