Substrats neuronaux du traitement visuel et sémantique des mots dans le vieillissement normal : apports de la MEG

Bien que l’on ait longtemps considéré que les substrats cérébraux de la mémoire sémantique (MS) demeuraient intacts au cours du vieillissement normal (VN), en raison d’une préservation de la performance des personnes âgées à des épreuves sémantiques, plusieurs études récentes suggèrent que des modifications cérébrales sous-tendant le traitement sémantique opèrent au cours du vieillissement. Celles-ci toucheraient principalement les régions responsables des aspects exécutifs du traitement sémantique, impliqués dans les processus de recherche, de sélection et de manipulation stratégique de l’information sémantique. Cependant, les mécanismes spécifiques régissant la réorganisation cérébrale du traitement sémantique au cours du VN demeurent méconnus, notamment en raison de divergences méthodologiques entre les études. De plus, des données de la littérature suggèrent que des modifications cérébrales associées au vieillissement pourraient également avoir lieu en relation avec les aspects perceptifs visuels du traitement des mots. Puisque le processus de lecture des mots représente un processus interactif et dynamique entre les fonctions perceptuelles de bas niveau et les fonctions de plus haut niveau tel que la MS, il pourrait exister des modifications liées à l’âge au plan des interactions cérébrales entre les aspects perceptifs et sémantiques du traitement des mots. Dans son ensemble, l’objectif de la présente thèse était de caractériser les modifications cérébrales ainsi que le décours temporel du signal cérébral qui sont associés au traitement sémantique ainsi qu’au traitement perceptif des mots en lien avec le VN, ainsi que les relations et les modulations entre les processus sémantiques et perceptifs au cours du VN, en utilisant la magnétoencéphalographie (MEG) comme technique d’investigation. Dans un premier temps (chapitre 2), les patrons d’activation cérébrale d’un groupe de participants jeunes et d’un groupe de participants âgés sains ont été comparés alors qu’ils effectuaient une tâche de jugement sémantique sur des mots en MEG, en se concentrant sur le signal autour de la N400, une composante associée au traitement sémantique. Les résultats démontrent que des modifications cérébrales liées à l’âge touchent principalement les structures impliquées dans les aspects exécutifs du traitement sémantique. Une activation plus importante du cortex préfrontal inférieur (IPC) a été observée chez les participants jeunes que chez les participants âgés, alors que ces derniers activaient davantage les régions temporo-pariétales que les jeunes adultes. Par ailleurs, le lobe temporal antérieur (ATL) gauche, considéré comme une région centrale et amodale du traitement sémantique, était également davantage activé par les participants âgés que par les jeunes adultes. Dans un deuxième temps (chapitre 3), les patrons d’activation cérébrale d’un groupe de participants jeunes et d’un groupe de participants âgés sains ont été comparés en se concentrant sur le signal associé au traitement perceptif visuel, soit dans les 200 premières millisecondes du traitement des mots. Les résultats montrent que des modifications cérébrales liées à l’âge touchent le gyrus fusiforme mais aussi le réseau sémantique, avec une plus grande activation pour le groupe de participants âgés, malgré une absence de différence d’activation dans le cortex visuel extrastrié entre les deux groupes. Les implications théoriques des résultats de ces deux études sont ensuite discutées, et les limites et perspectives futures sont finalement adressées (chapitre 4).

Changes in cortical and sub-cortical patterns of activity associated with aging during the performance of a lexical set-shifting task

Bien que le passage du temps altère le cerveau, la cognition ne suit pas nécessairement le même destin. En effet, il existe des mécanismes compensatoires qui permettent de préserver la cognition (réserve cognitive) malgré le vieillissement. Les personnes âgées peuvent utiliser de nouveaux circuits neuronaux (compensation neuronale) ou des circuits existants moins susceptibles aux effets du vieillissement (réserve neuronale) pour maintenir un haut niveau de performance cognitive. Toutefois, la façon dont ces mécanismes affectent l’activité corticale et striatale lors de tâches impliquant des changements de règles (set-shifting) et durant le traitement sémantique et phonologique n’a pas été extensivement explorée. Le but de cette thèse est d’explorer comment le vieillissement affecte les patrons d’activité cérébrale dans les processus exécutifs d’une part et dans l’utilisation de règles lexicales d’autre part. Pour cela nous avons utilisé l’imagerie par résonance magnétique fonctionnelle (IRMf) lors de la performance d’une tâche lexicale analogue à celle du Wisconsin. Cette tâche a été fortement liée à de l’activité fronto-stritale lors des changements de règles, ainsi qu’à la mobilisation de régions associées au traitement sémantique et phonologique lors de décisions sémantiques et phonologiques, respectivement. Par conséquent, nous avons comparé l’activité cérébrale de jeunes individus (18 à 35 ans) à celle d’individus âgés (55 à 75 ans) lors de l’exécution de cette tâche. Les deux groupes ont montré l’implication de boucles fronto-striatales associées à la planification et à l’exécution de changements de règle. Toutefois, alors que les jeunes semblaient activer une « boucle cognitive » (cortex préfrontal ventrolatéral, noyau caudé et thalamus) lorsqu’ils se voyaient indiquer qu’un changement de règle était requis, et une « boucle motrice » (cortex postérieur préfrontal et putamen) lorsqu’ils devaient effectuer le changement, les participants âgés montraient une activation des deux boucles lors de l’exécution des changements de règle seulement. Les jeunes adultes tendaient à présenter une augmentation de l’activité du cortex préfrontal ventrolatéral, du gyrus fusiforme, du lobe ventral temporale et du noyau caudé lors des décisions sémantiques, ainsi que de l’activité au niveau de l’aire de Broca postérieur, de la junction temporopariétale et du cortex moteur lors de décisions phonologiques. Les participants âgés ont montré de l’activité au niveau du cortex préfrontal latéral et moteur durant les deux types de décisions lexicales. De plus, lorsque les décisions sémantiques et phonologiques ont été comparées entre elles, les jeunes ont montré des différences significatives au niveau de plusieurs régions cérébrales, mais pas les âgés. En conclusion, notre première étude a montré, lors du set-shifting, un délai de l’activité cérébrale chez les personnes âgées. Cela nous a permis de conceptualiser l’Hypothèse Temporelle de Compensation (troisième manuscrit) qui consiste en l’existence d’un mécanisme compensatoire caractérisé par un délai d’activité cérébrale lié au vieillissement permettant de préserver la cognition au détriment de la vitesse d’exécution. En ce qui concerne les processus langagiers (deuxième étude), les circuits sémantiques et phonologiques semblent se fusionner dans un seul circuit chez les individus âgés, cela représente vraisemblablement des mécanismes de réserve et de compensation neuronales qui permettent de préserver les habilités langagières.

Le rôle de la méthylation de l’ADN dans les fonctions cérébrales fronto-limbiques et la réactivité au stress quotidien

La sérotonine (5-HT) joue un rôle crucial dans l'étiologie des troubles mentaux comme la dépression majeure, les troubles de comportement et les troubles anxieux. Des études ont montré que des altérations précoces du système 5-HT peuvent potentiellement influencer le développement du cerveau et le fonctionnement du système fronto-limbique, engendrant des conséquences pour la régulation émotionnelle. Il existe aussi des évidences que le stress précoce peut affecter la méthylation de l'ADN résultant d'une altération de l'expression génique. Toutefois, le lien entre la méthylation de l'ADN et la réactivité comportementale à des facteurs de stress de la vie quotidienne est inconnu. La méthylation du gène transporteur 5-HT (SLC6A4) est d'un intérêt particulier, étant donné le rôle de SLC6A4 dans le développement du cerveau, les troubles mentaux et la régulation du stress. L'objectif de cette thèse est d'étudier l'association entre (1) les niveaux périphériques de méthylation de l'ADN dans le gène SLC6A4 et les réponses neurales aux stimuli émotionnels dans les circuits fronto-limbiques du cerveau, ainsi qu’entre (2) la méthylation périphérique de SLC6A4 et la réactivité comportementale au stress de la vie quotidienne. Nous explorons également l'association entre les réponses neuronales fronto-limbique à des stimuli émotionnels et la réactivité comportementale au stress de la vie quotidienne (3). À cette fin, vingt-deux personnes (11 femmes) d’âge moyen de 34,0 ans (SD : 1,5) avec différents niveaux de méthylation au gène SLC6A4 ont été recrutés à partir de deux études longitudinales. Les participants ont subi une analyse IRMf qui comprenait une tâche de traitement émotionnel. Un questionnaire en ligne sur la réactivité au stress quotidien de la vie a été réalisé pendant 5 jours consécutifs. Des analyses corrélationnelles et de régression ont été effectuées pour examiner les associations entre les variables primaires. Les résultats préliminaires de cette étude ont montré que la méthylation de l'ADN est associée à la désactivation significative du gyrus précentral et gyrus fusiforme respectivement face à des stimuli de peur et de tristesse. Aucune association significative n'a été observée entre les niveaux de méthylation et l'activation de l'amygdale. En outre, les scores obtenus aux variables de stress de la vie quotidienne tels que la détresse chronique ont été associées à la désactivation du précuneus et du cortex cingulaire postérieur face à la tristesse. Ces résultats suggèrent l'implication potentielle des processus épigénétiques dans l'activation cérébrale spécifique et la sensibilité au stress de la vie courante.

Neural responses to emotional faces in women recovered from anorexia nervosa

Impairments in emotional processing have been associated with anorexia nervosa. However, it is unknown whether neural and behavioural differences in the processing of emotional stimuli persist following recovery. The aim of this study was to investigate the neural processing of emotional faces in individuals recovered from anorexia nervosa compared with healthy controls. Thirty-two participants (16 recovered anorexia nervosa, 16 healthy controls) underwent a functional magnetic resonance imaging (fMRI) scan. Participants viewed fearful and happy emotional faces and indicated the gender of the face presented. Whole brain analysis revealed no significant differences between the groups to the contrasts of fear versus happy and vice versa. Region of interest analysis demonstrated no significant differences in the neural response to happy or fearful stimuli between the groups in the amygdala or fusiform gyrus. These results suggest that processing of emotional faces may not be aberrant after recovery from anorexia nervosa.

Atypical processing of voice sounds in infants at risk for Autism Spectrum Disorder

Adults diagnosed with autism spectrum disorder (ASD) show a reduced sensitivity (degree of selective response) to social stimuli such as human voices. In order to determine whether this reduced sensitivity is a consequence of years of poor social interaction and communication or is present prior to significant experience, we used functional MRI to examine cortical sensitivity to auditory stimuli in infants at high familial risk for later emerging ASD (HR group, N = 15), and compared this to infants with no family history of ASD (LR group, N = 18). The infants (aged between 4 and 7 months) were presented with voice and environmental sounds while asleep in the scanner and their behaviour was also examined in the context of observed parent-infant interaction. Whereas LR infants showed early specialisation for human voice processing in right temporal and medial frontal regions, the HR infants did not. Similarly, LR infants showed stronger sensitivity than HR infants to sad vocalisations in the right fusiform gyrus and left hippocampus. Also, in the HR group only, there was an association between each infant's degree of engagement during social interaction and the degree of voice sensitivity in key cortical regions. These results suggest that at least some infants at high-risk for ASD have atypical neural responses to human voice with and without emotional valence. Further exploration of the relationship between behaviour during social interaction and voice processing may help better understand the mechanisms that lead to different outcomes in at risk populations.

Nonlinear estimation of neural processing time from BOLD signal with application to decision-making

The extraction of information about neural activity timing from BOLD signal is a challenging task as the shape of the BOLD curve does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. The face validity and applicability of the concept of NPT are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. The experiment that was analyzed consisted of a decision-making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas, like the fusiform gyrus, is approximately the stimulus presentation duration. On the other hand, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the NPT in right but not left dorsal lateral prefrontal cortex depends on the stimulus emotional content. The summary measures of HRF obtained by a standard approach did not detect the variations observed in the NPT. Hum Brain Mapp, 2012. (C) 2010 Wiley Periodicals, Inc.

Neuroelectromagnetic correlates of perceptual closure processes

Perceptual closure refers to the coherent perception of an object under circumstances when the visual information is incomplete. Although the perceptual closure index observed in electroencephalography reflects that an object has been recognized, the full spatiotemporal dynamics of cortical source activity underlying perceptual closure processing remain unknown so far. To address this question, we recorded magnetoencephalographic activity in 15 subjects (11 females) during a visual closure task and performed beamforming over a sequence of successive short time windows to localize high-frequency gamma-band activity (60–100 Hz). Two-tone images of human faces (Mooney faces) were used to examine perceptual closure. Event-related fields exhibited a magnetic closure index between 250 and 325 ms. Time-frequency analyses revealed sustained high-frequency gamma-band activity associated with the processing of Mooney stimuli; closure-related gamma-band activity was observed between 200 and 300 ms over occipitotemporal channels. Time-resolved source reconstruction revealed an early (0–200 ms) coactivation of caudal inferior temporal gyrus (cITG) and regions in posterior parietal cortex (PPC). At the time of perceptual closure (200–400 ms), the activation in cITG extended to the fusiform gyrus, if a face was perceived. Our data provide the first electrophysiological evidence that perceptual closure for Mooney faces starts with an interaction between areas related to processing of three-dimensional structure from shading cues (cITG) and areas associated with the activation of long-term memory templates (PPC). Later, at the moment of perceptual closure, inferior temporal cortex areas specialized for the perceived object are activated, i.e., the fusiform gyrus related to face processing for Mooney stimuli.

The word-length effect in acquired alexia, and real and virtual hemianopia

A word-length effect is often described in pure alexia, with reading time proportional to the number of letters in a word. Given the frequent association of right hemianopia with pure alexia, it is uncertain whether and how much of the word-length effect may be attributable to the hemifield loss. To isolate the contribution of the visual field defect, we simulated hemianopia in healthy subjects with a gaze-contingent paradigm during an eye-tracking experiment. We found a minimal word-length effect of 14 ms/letter for full-field viewing, which increased to 38 ms/letter in right hemianopia and to 31 ms/letter in left hemianopia. We found a correlation between mean reading time and the slope of the word-length effect in hemianopic conditions. The 95% upper prediction limits for the word-length effect were 51 ms/letter in subjects with full visual fields and 161 ms/letter with simulated right hemianopia. These limits, which can be considered diagnostic criteria for an alexic word-length effect, were consistent with the reading performance of six patients with diagnoses based independently on perimetric and imaging data: two patients with probable hemianopic dyslexia, and four with alexia and lesions of the left fusiform gyrus, two with and two without hemianopia. Two of these patients also showed reduction of the word-length effect over months, one with and one without a reading rehabilitation program. Our findings clarify the magnitude of the word-length effect that originates from hemianopia alone, and show that the criteria for a word-length effect indicative of alexia differ according to the degree of associated hemifield loss.

Social Cognition And Functional Brain Imaging: Extending The Broader Autism Phenotype

Evidence suggests that the social cognition deficits prevalent in autism spectrum disorders (ASDs) are widely distributed in first degree and extended relatives. This ¿broader autism phenotype¿ (BAP) can be extended into non-clinical populations and show wide distributions of social behaviors such as empathy and social responsiveness ¿ with ASDs exhibiting these behaviors on the lower ends of the distributions. Little evidence has previously shown relationships between self-report measures of social cognition and more objective tasks such as face perception in functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs). In this study, three specific hypotheses were addressed: a) increased social ability, as measured by an increased Empathy Quotient, decreased Social Responsiveness Scale (SRS-A) score, and increased Social Attribution Task score, will predict increased activation of the fusiform gyrus in response to faces as compared to houses; b) these same measures will predict N170 amplitude and latency showing decreased latency and increased amplitude for faces as compared to houses with increased social ability; c) increased amygdala volume will predict increased fusiform gyrus activation when viewing faces as compared to houses. Findings supported all of the hypotheses. Empathy scores significantly predicted both right FFG activation [F(1,20) = 4.811, p = .041, ß = .450, R2 = 0.20] and left FFG activation [F(1,20) = 7.70, p = .012, ß = .537, R2 = 0.29]. Based on ERP results increased right lateralization face-related N170 was significantly predicted by the EQ [F(1,54) = 6.94, p = .011, ß = .338, R2 = 0.11]. Finally, total amygdala volume significantly predicted right [F(1,20) = 7.217, p = .014, ß = .515, R2 = 0.27] and left [F(1,20) = 36.77, p < .001, ß = .805, R2 = 0.65] FFG activation. Consistent with the a priori hypotheses, traits attributed to the BAP can significantly predict neural responses to faces in a non-clinical population. This is consistent with the face processing deficits seen in ASDs. The findings presented here contribute to the extension of the BAP from unaffected relatives of individuals with ASDs to the general population. These findings also give continued evidence in support of a continuous distribution of traits found in psychiatric illnesses in place of a traditional, dichotomous ¿all-or-nothing¿ diagnostic framework of neurodevelopmental and neuropsychiatric disorders.

Social Cognition and Neural Substrates of Face Perception: Implications for Neurodevelopmental and Neuropsychiatric Disorders

BACKGROUND: Social cognition is an important aspect of social behavior in humans. Social cognitive deficits are associated with neurodevelopmental and neuropsychiatric disorders. In this study we examine the neural substrates of social cognition and face processing in a group of healthy young adults to examine the neural substrates of social cognition. METHODS: Fifty-seven undergraduates completed a battery of social cognition tasks and were assessed with electroencephalography (EEG) during a face-perception task. A subset (N=22) were administered a face-perception task during functional magnetic resonance imaging. RESULTS: Variance in the N170 EEG was predicted by social attribution performance and by a quantitative measure of empathy. Neurally, face processing was more bilateral in females than in males. Variance in fMRI voxel count in the face-sensitive fusiform gyrus was predicted by quantitative measures of social behavior, including the Social Responsiveness Scale (SRS) and the Empathizing Quotient. CONCLUSIONS: When measured as a quantitative trait, social behaviors in typical and pathological populations share common neural pathways. The results highlight the importance of viewing neurodevelopmental and neuropsychiatric disorders as spectrum phenomena that may be informed by studies of the normal distribution of relevant traits in the general population. Copyright 2014 Elsevier B.V. All rights reserved.

Patterns of regional brain hypometabolism associated with knowledge of semantic features and categories in Alzheimer's disease

The study of semantic memory in patients with Alzheimer's disease (AD) has raised important questions about the representation of conceptual knowledge in the human brain. It is still unknown whether semantic memory impairments are caused by localized damage to specialized regions or by diffuse damage to distributed representations within nonspecialized brain areas. To our knowledge, there have been no direct correlations of neuroimaging of in vivo brain function in AD with performance on tasks differentially addressing visual and functional knowledge of living and nonliving concepts. We used a semantic verification task and resting 18-fluorodeoxyglucose positron emission tomography in a group of mild to moderate AD patients to investigate this issue. The four task conditions required semantic knowledge of (1) visual, (2) functional properties of living objects, and (3) visual or (4) functional properties of nonliving objects. Visual property verification of living objects was significantly correlated with left posterior fusiform gyrus metabolism (Brodmann's area [BA] 37/19). Effects of visual and functional property verification for non-living objects largely overlapped in the left anterior temporal (BA 38/20) and bilateral premotor areas (BA 6), with the visual condition extending more into left lateral precentral areas. There were no associations with functional property verification for living concepts. Our results provide strong support for anatomically separable representations of living and nonliving concepts, as well as visual feature knowledge of living objects, and against distributed accounts of semantic memory that view visual and functional features of living and nonliving objects as distributed across a common set of brain areas.

Functional imbalance of visual pathways indicates alternative face processing strategies in autism

OBJECTIVE: To investigate whether autistic subjects show a different pattern of neural activity than healthy individuals during processing of faces and complex patterns. METHODS: Blood oxygen level-dependent (BOLD) signal changes accompanying visual processing of faces and complex patterns were analyzed in an autistic group (n = 7; 25.3 [6.9] years) and a control group (n = 7; 27.7 [7.8] years). RESULTS: Compared with unaffected subjects, autistic subjects demonstrated lower BOLD signals in the fusiform gyrus, most prominently during face processing, and higher signals in the more object-related medial occipital gyrus. Further signal increases in autistic subjects vs controls were found in regions highly important for visual search: the superior parietal lobule and the medial frontal gyrus, where the frontal eye fields are located. CONCLUSIONS: The cortical activation pattern during face processing indicates deficits in the face-specific regions, with higher activations in regions involved in visual search. These findings reflect different strategies for visual processing, supporting models that propose a predisposition to local rather than global modes of information processing in autism.

About the role of visual field defects in pure alexia

Pure alexia is an acquired reading disorder characterized by a disproportionate prolongation of reading time as a function of word length. Although the vast majority of cases reported in the literature show a right-sided visual defect, little is known about the contribution of this low-level visual impairment to their reading difficulties. The present study was aimed at investigating this issue by comparing eye movement patterns during text reading in six patients with pure alexia with those of six patients with hemianopic dyslexia showing similar right-sided visual field defects. We found that the role of the field defect in the reading difficulties of pure alexics was highly deficit-specific. While the amplitude of rightward saccades during text reading seems largely determined by the restricted visual field, other visuo-motor impairments-particularly the pronounced increases in fixation frequency and viewing time as a function of word length-may have little to do with their visual field defect. In addition, subtracting the lesions of the hemianopic dyslexics from those found in pure alexics revealed the largest group differences in posterior parts of the left fusiform gyrus, occipito-temporal sulcus and inferior temporal gyrus. These regions included the coordinate assigned to the centre of the visual word form area in healthy adults, which provides further evidence for a relation between pure alexia and a damaged visual word form area. Finally, we propose a list of three criteria that may improve the differential diagnosis of pure alexia and allow appropriate therapy recommendations.

The emotional power of music: How music enhances the feeling of affective pictures

Music is an intriguing stimulus widely used in movies to increase the emotional experience. However, no brain imaging study has to date examined this enhancement effect using emotional pictures (the modality mostly used in emotion research) and musical excerpts. Therefore, we designed this functional magnetic resonance imaging study to explore how musical stimuli enhance the feeling of affective pictures. In a classical block design carefully controlling for habituation and order effects, we presented fearful and sad pictures (mostly taken from the IAPS) either alone or combined with congruent emotional musical excerpts (classical pieces). Subjective ratings clearly indicated that the emotional experience was markedly increased in the combined relative to the picture condition. Furthermore, using a second-level analysis and regions of interest approach, we observed a clear functional and structural dissociation between the combined and the picture condition. Besides increased activation in brain areas known to be involved in auditory as well as in neutral and emotional visual-auditory integration processes, the combined condition showed increased activation in many structures known to be involved in emotion processing (including for example amygdala, hippocampus, parahippocampus, insula, striatum, medial ventral frontal cortex, cerebellum, fusiform gyrus). In contrast, the picture condition only showed an activation increase in the cognitive part of the prefrontal cortex, mainly in the right dorsolateral prefrontal cortex. Based on these findings, we suggest that emotional pictures evoke a more cognitive mode of emotion perception, whereas congruent presentations of emotional visual and musical stimuli rather automatically evoke strong emotional feelings and experiences.

Modulation of anticipatory emotion and perception processing by cognitive control.

Strategies of cognitive control are helpful in reducing anxiety experienced during anticipation of unpleasant or potentially unpleasant events. We investigated the associated cerebral information processing underlying the use of a specific cognitive control strategy during the anticipation of affect-laden events. Using functional magnetic resonance imaging, we examined differential brain activity during anticipation of events of unknown and negative emotional valence in a group of eighteen healthy subjects that used a cognitive control strategy, similar to "reality checking" as used in psychotherapy, compared with a group of sixteen subjects that did not exert cognitive control. While expecting unpleasant stimuli, the "cognitive control" group showed higher activity in left medial and dorsolateral prefrontal cortex areas but reduced activity in the left extended amygdala, pulvinar/lateral geniculate nucleus and fusiform gyrus. Cognitive control during the "unknown" expectation was associated with reduced amygdalar activity as well and further with reduced insular and thalamic activity. The amygdala activations associated with cognitive control correlated negatively with the reappraisal scores of an emotion regulation questionnaire. The results indicate that cognitive control of particularly unpleasant emotions is associated with elevated prefrontal cortex activity that may serve to attenuate emotion processing in for instance amygdala, and, notably, in perception related brain areas.