Although social cognitive impairments are key determinants of functional outcome in schizophrenia their neural bases are poorly understood. This study investigated neural activity during imitation and observation of finger movements and facial expressions in schizophrenia, and their correlates with self-reported empathy.
23 schizophrenia outpatients and 23 healthy controls were studied with functional magnetic resonance imaging (fMRI) while they imitated, executed, or simply observed finger movements and facial emotional expressions. Between-group activation differences, as well as relationships between activation and self-reported empathy, were evaluated.
Both patients and controls similarly activated neural systems previously associated with these tasks. We found no significant between-group differences in task-related activations. There were, however, between-group differences in the correlation between self-reported empathy and right inferior frontal (pars opercularis) activity during observation of facial emotional expressions. As in previous studies, controls demonstrated a positive association between brain activity and empathy scores. In contrast, the pattern in the patient group reflected a negative association between brain activity and empathy.
Although patients with schizophrenia demonstrated largely normal patterns of neural activation across the finger movement and facial expression tasks, they reported decreased self perceived empathy and failed to show the typical relationship between neural activity and self-reported empathy seen in controls. These findings suggest that patients show a disjunction between automatic neural responses to low level social cues and higher level, integrative social cognitive processes involved in self-perceived empathy.
•Comparable activation patterns were present in both groups for finger and facial stimuli.•There were no group differences on any of the activation tasks.•Self-reported empathy differentially related to neural activation in the two groups.•Empathy related to right inferior frontal activity in controls but not in patients.•Patients showed a disconnect between low- and high-level social cognitive processes.
Imitation; Observation; Simulation; Schizophrenia; Mirror neuron system; Empathy
The mechanisms through which people perceive different types of smiles and judge their authenticity remain unclear. Here, 19 different types of smiles were created based on the Facial Action Coding System (FACS), using highly controlled, dynamic avatar faces. Participants observed short videos of smiles while their facial mimicry was measured with electromyography (EMG) over four facial muscles. Smile authenticity was judged after each trial. Avatar attractiveness was judged once in response to each avatar’s neutral face. Results suggest that, in contrast to most earlier work using static pictures as stimuli, participants relied less on the Duchenne marker (the presence of crow’s feet wrinkles around the eyes) in their judgments of authenticity. Furthermore, mimicry of smiles occurred in the Zygomaticus Major, Orbicularis Oculi, and Corrugator muscles. Consistent with theories of embodied cognition, activity in these muscles predicted authenticity judgments, suggesting that facial mimicry influences the perception of smiles. However, no significant mediation effect of facial mimicry was found. Avatar attractiveness did not predict authenticity judgments or mimicry patterns.
The two major brain networks, i.e., the default mode network (DMN) and the task positive network, typically reveal negative and variable connectivity in resting-state. In the present study, we examined whether the connectivity between the DMN and different components of the task positive network were modulated by other brain regions by using physiophysiological interaction (PPI) on resting-state functional magnetic resonance imaging data. Spatial independent component analysis was first conducted to identify components that represented networks of interest, including the anterior and posterior DMNs, salience, dorsal attention, left and right executive networks. PPI analysis was conducted between pairs of these networks to identify networks or regions that showed modulatory interactions with the two networks. Both network-wise and voxel-wise analyses revealed reciprocal positive modulatory interactions between the DMN, salience, and executive networks. Together with the anatomical properties of the salience network regions, the results suggest that the salience network may modulate the relationship between the DMN and executive networks. In addition, voxel-wise analysis demonstrated that the basal ganglia and thalamus positively interacted with the salience network and the dorsal attention network, and negatively interacted with the salience network and the DMN. The results demonstrated complex modulatory interactions among the DMNs and task positive networks in resting-state, and suggested that communications between these networks may be modulated by some critical brain structures such as the salience network, basal ganglia, and thalamus.
Dynamic connectivity; Salience network; Thalamus; Physiophysiological interaction; Basal ganglia; Modulatory interaction
Social and communication impairments are part of the essential diagnostic criteria used to define Autism Spectrum Disorders (ASDs). Difficulties in appreciating non-literal speech, such as irony in ASDs have been explained as due to impairments in social understanding and in recognizing the speaker’s communicative intention. It has been shown that social-interactional factors, such as a listener’s beliefs about the speaker’s attitudinal propensities (e.g., a tendency to use sarcasm, to be mocking, less sincere and more prone to criticism), as conveyed by an occupational stereotype, do influence a listener’s interpretation of potentially ironic remarks. We investigate the effect of occupational stereotype on irony detection in adults with High Functioning Autism or Asperger Syndrome (HFA/AS) and a comparison group of typically developed adults. We used a series of verbally presented stories containing ironic or literal utterances produced by a speaker having either a “sarcastic” or a “non-sarcastic” occupation. Although individuals with HFA/AS were able to recognize ironic intent and occupational stereotypes when the latter are made salient, stereotype information enhanced irony detection and modulated its social meaning (i.e., mockery and politeness) only in comparison participants. We concluded that when stereotype knowledge is not made salient, it does not automatically affect pragmatic communicative processes in individuals with HFA/AS.
Recent research suggests that facial mimicry underlies accurate interpretation of subtle facial expressions. In three experiments, we manipulated mimicry and tested its role in judgments of the genuineness of true and false smiles. Experiment 1 used facial EMG to show that a new mouthguard technique for blocking mimicry modifies both the amount and the time course of facial reactions. In Experiments 2 and 3, participants rated true and false smiles either while wearing mouthguards or when allowed to freely mimic the smiles with or without additional distraction, namely holding a squeeze ball or wearing a finger-cuff heart rate monitor. Results showed that blocking mimicry compromised the decoding of true and false smiles such that they were judged as equally genuine. Together the experiments highlight the role of facial mimicry in judging subtle meanings of facial expressions.
Since the discovery of mirror neurons in premotor and parietal areas of the macaque monkey, the idea that action and perception may share the same neural code has been of central interest in social, developmental, and cognitive neurosciences. A fundamental question concerns how a putative human mirror neuron system may be tuned to the motor experiences of the individual. The current study tested the hypothesis that prior motor experience modulated the sensorimotor mu and beta rhythms. Specifically, we hypothesized that these sensorimotor rhythms would be more desynchronized after active motor experience compared to passive observation experience. To test our hypothesis, we collected EEG from adult participants during the observation of a relatively novel action: an experimenter used a claw-like tool to pick up a toy. Prior to EEG collection, we trained one group of adults to perform this action with the tool (performers). A second group comprised trained video coders, who only had experience observing the action (observers). Both the performers and the observers had no prior motor and visual experience with the action. A third group of novices was also tested. Performers exhibited the greatest mu rhythm desynchronization in the 8–13 Hz band, particularly in the right hemisphere compared to observers and novices. This study is the first to contrast active tool-use experience and observation experience in the mu rhythm and to show modulation with relatively shorter amounts of experience than prior mirror neuron expertise studies. These findings are discussed with respect to its broader implication as a neural signature for a mechanism of early social learning.
More empathetic physicians are more likely to achieve higher patient satisfaction, adherence to treatments, and health outcomes. In the context of medical education, it is thus important to understand how personality might condition the empathetic development of medical students. Single institutional evidence shows associations between students' personality and empathy. This multi-institutional study aimed to assess such associations across institutions, looking for personality differences between students with high empathy and low empathy levels.
Participants were 472 students from three medical schools in Portugal. They completed validated adaptations to Portuguese of self-report measures of the NEO-Five Factor Inventory(NEO-FFI) and the Jefferson Scale of Physician Empathy(JSPE-spv). Students were categorized into two groups: “Bottom” (low empathy, N = 165) and “Top” (high empathy, N = 169) according to their empathy JSPE-spv total score terciles. Correlation analysis, binary logistic regression analysis and ROC curve analysis were conducted.
A regression model with gender, age and university had a predictive power (pseudo R2) for belonging to the top or bottom group of 6.4%. The addition of personality dimensions improved the predictive power to 16.8%. Openness to experience and Agreeableness were important to predict top or bottom empathy scores when gender, age and university were considered.” Based on the considered predictors the model correctly classified 69.3% of all students.
The present multi-institutional cross-sectional study in Portugal revealed across-school associations between the Big5 dimensions Agreeableness and Openness to experience and the empathy of medical students and that personality made a significant contribution to identify the more empathic students. Therefore, medical schools may need to pay attention to the personality of medical students to understand how to enhance the empathy of medical students.
Imitation plays a central role in the acquisition of culture. People preferentially imitate others who are self-similar, prestigious or successful. Because race can indicate a person's self-similarity or status, race influences whom people imitate. Prior studies of the neural underpinnings of imitation have not considered the effects of race. Here we measured neural activity with fMRI while European American participants imitated meaningless gestures performed by actors of their own race, and two racial outgroups, African American, and Chinese American. Participants also passively observed the actions of these actors and their portraits. Frontal, parietal and occipital areas were differentially activated while participants imitated actors of different races. More activity was present when imitating African Americans than the other racial groups, perhaps reflecting participants' reported lack of experience with and negative attitudes towards this group, or the group's lower perceived social status. This pattern of neural activity was not found when participants passively observed the gestures of the actors or simply looked at their faces. Instead, during face-viewing neural responses were overall greater for own-race individuals, consistent with prior race perception studies not involving imitation. Our findings represent a first step in elucidating neural mechanisms involved in cultural learning, a process that influences almost every aspect of our lives but has thus far received little neuroscientific study.
Race; Imitation; Mirror neuron system; Neuroimaging; Cultural learning
Using functional magnetic resonance imaging, we show that a distributed fronto-parietal visuomotor integration network is recruited to overcome automatic responses to both biological and non-biological cues. Activity levels in these areas are similar for both cue types. The functional connectivity of this network, however, reveals differential coupling with thalamus and precuneus (biological cues) and extrastriate cortex (non biological cues). This suggests that a set of cortical areas equally activated in two tasks may accomplish task goals differently depending on their network interactions. This supports models of brain organization that emphasize efficient coding through changing patterns of integration between regions of specialized function.
Imitative Behavior; Functional MRI; Space Perception; Intention; Executive Function
Objective. To explore the influences of discrete positive and negative emotions on cooperation in the context of a social dilemma game.
Design. Two controlled studies were undertaken. In Study 1, 69 participants were randomly assigned to an essay emotion manipulation task designed to induce either guilt, joy or no strong emotion. In Study 2, 95 participants were randomly assigned to one of the same three tasks, and the impact of emotional condition on cooperation was explored using a repeated Prisoner’s Dilemma Game.
Results. Study 1 established that the manipulation task was successful in inducing the specified emotions. The analysis from Study 2 revealed no significant main effects for emotions, in contrast to previous research. However, there was a significant effect for participants’ pre-existing tendency to cooperate (social value orientation; SVO).
Conclusion. Methodological explanations for the result are explored, including the possible impact of trial-and-error strategies, different cooperation games and endogenous vs exogenous emotions.
Well-being; Positive and negative emotions; Cooperation; Social dilemma games
Adolescence is often described as a period of heightened reactivity to emotions paired with reduced regulatory capacities, a combination suggested to contribute to risk-taking and susceptibility to peer influence during puberty. However, no longitudinal research has definitively linked these behavioral changes to underlying neural development. Here, 38 neurotypical participants underwent two fMRI sessions across the transition from late childhood (10 years) to early adolescence (13 years). Responses to affective facial displays exhibited a combination of general and emotion-specific changes in ventral striatum (VS), ventromedial PFC, amygdala, and temporal pole. Furthermore, VS activity increases correlated with decreases in susceptibility to peer influence and risky behavior. VS and amygdala responses were also significantly more negatively coupled in early adolescence than in late childhood while processing sad and happy versus neutral faces. Together, these results suggest that VS responses to viewing emotions may play a regulatory role that is critical to adolescent interpersonal functioning.
The mirror neuron system (MNS) has been proposed to play an important role in social cognition by providing a neural mechanism by which others’ actions, intentions, and emotions can be understood. Here functional magnetic resonance imaging was used to directly examine the relationship between MNS activity and two distinct indicators of social functioning in typically-developing children (aged 10.1 years±7 months): empathy and interpersonal competence. Reliable activity in pars opercularis, the frontal component of the MNS, was elicited by observation and imitation of emotional expressions. Importantly, activity in this region (as well as in the anterior insula and amygdala) was significantly and positively correlated with established behavioral measures indexing children’s empathic behavior (during both imitation and observation) and interpersonal skills (during imitation only). These findings suggest that simulation mechanisms and the MNS may indeed be relevant to social functioning in everyday life during typical human development.
In the automatic imitation task (AIT) participants make a cued response during simultaneous exposure to a congruent or incongruent action made by another agent. Participants are slower to make the cued response on incongruent trials, which is thought to reflect conflict between the motor representation activated by the cue and the motor representation activated by the observed action. On incongruent trials, good performance requires the capacity to suppress the imitative action, in favor of producing the cued response. Here, we introduce a new experimental paradigm that complements the AIT, and is therefore a useful task for studying the control of self and other activated representations. In what we term the “Controlled Imitation Task (CIT)”, participants are cued to make an action, but on 50% of trials, within 100 ms of this cue, an on-screen hand makes a congruent or incongruent action. If the onscreen hand moves, the participant must suppress the cued response, and instead imitate the observed action as quickly and accurately as possible. In direct contrast to the AIT, the CIT requires suppression of a self-activated motor representation, and prioritization of an imitative response. In experiment 1, we report a robust pattern of interference effects in the CIT, such that participants are slower to make the imitative response on incongruent compared to congruent trials. In experiment 2, we replicate this effect while including a non-imitative spatial-cue control condition to show that the effect is particularly robust for imitative response tendencies per se. Owing to the essentially opposite control requirements of the CIT versus the AIT (i.e., suppression of self-activated motor representations instead of suppression of other-activated motor representations), we propose that this new task is a potentially informative complementary paradigm to the AIT that can be used in studies of self-other control processes.
Imitation; Automatic imitation; Controlled imitation; Mirror system; Motor resonance; Automatic imitation Task; Self-related processing; Other-related processing; Self-other control
Background. Normally one habituates rapidly to steady, faint sensations. People with sensory hypersensitivity (SH), by contrast, continue to attend to such stimuli and find them noxious. SH is common in Tourette syndrome (TS) and autism, and methods to quantify SH may lead to better understanding of these disorders. In an attempt to objectively quantify SH severity, the authors tested whether a choice reaction time (CRT) task was a sensitive enough measure to detect significant distraction from a steady tactile stimulus, and to detect significantly greater distraction in subjects with more severe SH.
Methods. Nineteen ambulatory adult volunteers with varying scores on the Adult Sensory Questionnaire (ASQ), a clinical measure of SH, completed a CRT task in the alternating presence and absence of tactile stimulation.
Results. Tactile stimulation interfered with attention (i.e., produced longer reaction times), and this effect was significantly greater in participants with more SH (higher ASQ scores). Accuracy on the CRT was high in blocks with and without stimulation. Habituation within stimulation blocks was not detected.
Conclusion. This approach can detect distraction from a cognitive task by a steady, faint tactile stimulus that does not degrade response accuracy. The method was also sensitive to the hypothesized enhancement of this effect by SH. These results support the potential utility of this approach to quantifying SH, and suggest possible refinements for future studies.
Attention; Sensory hypersensitivity; Habituation; Tourette syndrome; Reaction time; Tactile stimulation
To examine mirror neuron abnormalities in autism, high-functioning children with autism and matched controls underwent fMRI while imitating and observing emotional expressions. Although both groups performed the tasks equally well, children with autism showed no mirror neuron activity in the inferior frontal gyrus (pars opercularis). Notably, activity in this area was inversely related to symptom severity in the social domain, suggesting that a dysfunctional ‘mirror neuron system’ may underlie the social deficits observed in autism.
Parietal and premotor cortices of the macaque monkey contain distinct populations of neurons which, in addition to their motor discharge, are also activated by visual stimulation. Among these visuomotor neurons, a population of grasping neurons located in the anterior intraparietal area (AIP) shows discharge modulation when the own hand is visible during object grasping. Given the dense connections between AIP and inferior frontal regions, we aimed at investigating whether two hand-related frontal areas, ventral premotor area F5 and primary motor cortex (area F1), contain neurons with similar properties. Two macaques were involved in a grasping task executed in various light/dark conditions in which the to-be-grasped object was kept visible by a dim retro-illumination. Approximately 62% of F5 and 55% of F1 motor neurons showed light/dark modulations. To better isolate the effect of hand-related visual input, we introduced two further conditions characterized by kinematic features similar to the dark condition. The scene was briefly illuminated (i) during hand preshaping (pre-touch flash, PT-flash) and (ii) at hand-object contact (touch flash, T-flash). Approximately 48% of F5 and 44% of F1 motor neurons showed a flash-related modulation. Considering flash-modulated neurons in the two flash conditions, ∼40% from F5 and ∼52% from F1 showed stronger activity in PT- than T-flash (PT-flash-dominant), whereas ∼60% from F5 and ∼48% from F1 showed stronger activity in T- than PT-flash (T-flash-dominant). Furthermore, F5, but not F1, flash-dominant neurons were characterized by a higher peak and mean discharge in the preferred flash condition as compared to light and dark conditions. Still considering F5, the distribution of the time of peak discharge was similar in light and preferred flash conditions. This study shows that the frontal cortex contains neurons, previously classified as motor neurons, which are sensitive to the observation of meaningful phases of the own grasping action. We conclude by discussing the possible functional role of these populations.
Single-neuron recording; Grasping; Visuomotor; Frontal cortex
A growing body of evidence suggests that autism spectrum disorders (ASDs) are related to altered communication between brain regions. Here, we present findings showing that ASD is characterized by a pattern of reduced functional integration as well as reduced segregation of large-scale brain networks. Twenty-three children with ASD and 25 typically developing matched controls underwent functional magnetic resonance imaging while passively viewing emotional face expressions. We examined whole-brain functional connectivity of two brain structures previously implicated in emotional face processing in autism: the amygdala bilaterally and the right pars opercularis of the inferior frontal gyrus (rIFGpo). In the ASD group, we observed reduced functional integration (i.e., less long-range connectivity) between amygdala and secondary visual areas, as well as reduced segregation between amygdala and dorsolateral prefrontal cortex. For the rIFGpo seed, we observed reduced functional integration with parietal cortex and increased integration with right frontal cortex as well as right nucleus accumbens. Finally, we observed reduced segregation between rIFGpo and the ventromedial prefrontal cortex. We propose that a systems-level approach—whereby the integration and segregation of large-scale brain networks in ASD is examined in relation to typical development—may provide a more detailed characterization of the neural basis of ASD.
amygdala; connectivity; default mode network; face processing; mirror neuron system
The ability to process facial expressions can be modified by altering the spatial frequency of the stimuli, an effect that has been attributed to differential properties of visual pathways that convey different types of information to distinct brain regions at different speeds. While this effect suggests a potential influence of spatial frequency on the processing speed of facial emotion, this hypothesis has not been examined directly. We addressed this question using a facial emotion identification task with photographs containing either high spatial frequency (HSF), low spatial frequency (LSF), or broadband spatial frequency (BSF). Temporal processing of emotion perception was manipulated by suppressing visual perception with a single-pulse transcranial magnetic stimulation (TMS), delivered to the visual cortex at six intervals prior to (forward masking) or following (backward masking) stimulus presentation. Participants performed best in the BSF, followed by LSF, and finally HSF condition. A spatial frequency by forward/backward masking interaction effect demonstrated reduced performance in the forward masking component in the BSF condition and a reversed performance pattern in the HSF condition, with no significant differences between forward and backward masking in the LSF condition. Results indicate that LSF information may play a greater role than HSF information in emotional processing, but may not be sufficient for fast conscious perception of emotion. As both LSF and HSF filtering reduced the speed of extracting emotional information from faces, it is possible that intact BSF faces have an inherent perceptual advantage and hence benefit from faster temporal processing.
Affect perception; facial emotion; transcranial magnetic stimulation; visual masking
We used Support Vector Machine (SVM) to perform multivariate pattern classification based on brain activation during emotional processing in healthy participants with subclinical depressive symptoms. Six-hundred undergraduate students completed the Beck Depression Inventory II (BDI-II). Two groups were subsequently formed: (i) subclinical (mild) mood disturbance (n = 17) and (ii) no mood disturbance (n = 17). Participants also completed a self-report questionnaire on subclinical psychotic symptoms, the Community Assessment of Psychic Experiences Questionnaire (CAPE) positive subscale. The functional magnetic resonance imaging (fMRI) paradigm entailed passive viewing of negative emotional and neutral scenes. The pattern of brain activity during emotional processing allowed correct group classification with an overall accuracy of 77% (p = 0.002), within a network of regions including the amygdala, insula, anterior cingulate cortex and medial prefrontal cortex. However, further analysis suggested that the classification accuracy could also be explained by subclinical psychotic symptom scores (correlation with SVM weights r = 0.459, p = 0.006). Psychosis proneness may thus be a confounding factor for neuroimaging studies in subclinical depression.
Machine learning; Support vector machine; fMRI; Emotion; Subclinical depression; Psychosis proneness; Neuroimaging
Adolescence is marked by profound psychosocial and physiological changes. Although investigations into the interactions between these forces have begun to shed light on the neural correlates of affective processing during the transition to adolescence, relatively little is known about the relationship between pubertal development and emotion perception at the neural level. In the current longitudinal study, 45 neurotypical participants were shown affective facial displays while undergoing fMRI, at ages 10 and 13. Neural responses to emotional expressions at both time points were then correlated with a self-report measure of pubertal development, revealing positive associations with activity in amygdala, thalamus and visual cortical areas at age 10 that increased in magnitude and extent by age 13. At the latter time point, pubertal development was additionally correlated with enhanced responses to faces in temporal pole, ventrolateral prefrontal cortex (PFC) and dorsomedial PFC. Longitudinal comparisons revealed that the relationships between pubertal development and activity in the amygdala, hippocampus and temporal pole were significantly stronger during early adolescence than late childhood. These results suggest that pubertal development per se is linked to neural processing of socioemotional stimuli, particularly with respect to the integration of complex perceptual input and higher order cortical processing of affective content.
adolescence; puberty; emotion; fMRI; amygdala; longitudinal
Autism spectrum disorders (ASD) are characterized by significant social impairments, including deficits in orienting attention following social cues. Behavioral studies investigating social orienting in ASD, however, have yielded mixed results, as the use of naturalistic paradigms typically reveals clear deficits whereas computerized laboratory experiments often report normative behavior. The present study is the first to examine the neural mechanisms underlying social orienting in ASD in order to provide new insight into the social attention impairments that characterize this disorder. Using fMRI, we examined the neural correlates of social orienting in children and adolescents with ASD and in a matched sample of typically developing (TD) controls while they performed a spatial cueing paradigm with social (eye gaze) and nonsocial (arrow) cues. Cues were either directional (indicating left or right) or neutral (indicating no direction), and directional cues were uninformative of the upcoming target location in order to engage automatic processes by minimizing expectations. Behavioral results demonstrated intact orienting effects for social and nonsocial cues, with no differences between groups. The imaging results, however, revealed clear group differences in brain activity. When attention was directed by social cues compared to nonsocial cues, the TD group showed increased activity in frontoparietal attention networks, visual processing regions, and the striatum, whereas the ASD group only showed increased activity in the superior parietal lobule. Significant group × cue type interactions confirmed greater responsivity in task-relevant networks for social cues than nonsocial cues in TD as compared to ASD, despite similar behavioral performance. These results indicate that, in the autistic brain, social cues are not assigned the same privileged status as they are in the typically developing brain. These findings provide the first empirical evidence that the neural circuitry involved in social orienting is disrupted in ASD and highlight that normative behavioral performance in a laboratory setting may reflect compensatory mechanisms rather than intact social attention.
autism; attention; functional magnetic resonance imaging; gaze; social cue
The investigation of cultural phenomena using neuroscientific methods—cultural neuroscience (CN)—is receiving increasing attention. Yet it is unclear whether the integration of cultural study and neuroscience is merely additive, providing additional evidence of neural plasticity in the human brain, or truly synergistic, yielding discoveries that neither discipline could have achieved alone. We discuss how the parent fields to CN: cross-cultural psychology, psychological anthropology and cognitive neuroscience inform the investigation of the role of cultural experience in shaping the brain. Drawing on well-established methodologies from cross-cultural psychology and cognitive neuroscience, we outline a set of guidelines for CN, evaluate 17 CN studies in terms of these guidelines, and provide a summary table of our results. We conclude that the combination of culture and neuroscience is both additive and synergistic; while some CN methodologies and findings will represent the direct union of information from parent fields, CN studies employing the methodological rigor required by this logistically challenging new field have the potential to transform existing methodologies and produce unique findings.
cross-cultural; cross disciplinary; cultural-neuroscience; culture; neuroscience; neuroimaging
In the course of developing an atlas and reference system for the normal human brain throughout the human age span from structural and functional brain imaging data, the International Consortium for Brain Mapping (ICBM) developed a set of “normal” criteria for subject inclusion and the associated exclusion criteria. The approach was to minimize inclusion of subjects with any medical disorders that could affect brain structure or function. In the past two years, a group of 1,685 potential subjects responded to solicitation advertisements at one of the consortium sites (UCLA). Subjects were screened by a detailed telephone interview and then had an in-person history and physical examination. Of those who responded to the advertisement and considered themselves to be normal, only 31.6% (532 subjects) passed the telephone screening process. Of the 348 individuals who submitted to in-person history and physical examinations, only 51.7% passed these screening procedures. Thus, only 10.7% of those individuals who responded to the original advertisement qualified for imaging. The most frequent cause for exclusion in the second phase of subject screening was high blood pressure followed by abnormal signs on neurological examination. It is concluded that the majority of individuals who consider themselves normal by self-report are found not to be so by detailed historical interviews about underlying medical conditions and by thorough medical and neurological examinations. Recommendations are made with regard to the inclusion of subjects in brain imaging studies and the criteria used to select them.