Evaluation of the proposed anti-N-methyl-d-aspartate receptor encephalitis clinical diagnostic criteria in psychiatric patients.

OBJECTIVE: The gold standard for diagnosing anti-NMDAR encephalitis is demonstration of the antibody in CSF. Clinical diagnostic criteria have been proposed for when this is not available in a timely manner which is evaluated, in this study, for a psychiatric population. METHODS: This study retrospectively assessed the proposed criteria in patients presenting to psychiatric services for the first time with known anti-NMDAR antibody status. Antibody-positive cases were derived from the literature (conception to December 2019) and a state-wide (Queensland, Australia) cohort. Antibody-negative cases were derived from a service-wide (Metro South, Queensland, Australia) cohort of psychiatric cases which underwent antibody testing for routine organic screening. Sensitivity and specificity were calculated at 1 week following admission and the point of discharge. RESULTS: The proposed criteria were applied to 641 cases (500 antibody-positive and 141 antibody-negative), demonstrating a sensitivity which increased from around 19% after 1 week to 49% by the point of discharge. Specificity was 100% at both time points. The mean average time to become positive using the proposed criteria was 19.5 days compared to 34.9 days for return of antibody testing. CONCLUSIONS: High specificity of the proposed criteria, seen in this study, suggests that cases which are positive can be considered for expedited commencement of treatment. However, if clinical suspicion is high despite criteria being negative, it is essential to test CSF for anti-NMDAR antibody.

Group membership and racial bias modulate the temporal estimation of in-group/out-group body movements.

Social group categorization has been mainly studied in relation to ownership manipulations involving highly-salient multisensory cues. Here, we propose a novel paradigm that can implicitly activate the embodiment process in the presence of group affiliation information, whilst participants complete a task irrelevant to social categorization. Ethnically White participants watched videos of White- and Black-skinned models writing a proverb. The writing was interrupted 7, 4 or 1 s before completion. Participants were tasked with estimating the residual duration following interruption. A video showing only hand kinematic traces acted as a control condition. Residual duration estimates for out-group and control videos were significantly lower than those for in-group videos only for the longest duration. Moreover, stronger implicit racial bias was negatively correlated to estimates of residual duration for out-group videos. The underestimation bias for the out-group condition might be mediated by implicit embodiment, affective and attentional processes, and finalized to a rapid out-group categorization.

Frequent expression of the tumor necrosis factor receptor-associated factor 1 in latent membrane protein 1-positive posttransplant lymphoproliferative disease and HIV-associated lymphomas.

The tumor necrosis factor receptor-associated factor 1 (TRAF1) participates in the signal transduction of various members of the tumor necrosis factor receptor (TNFR) family, including TNFR2, CD40, CD30, and the Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1). In vitro, TRAF1 is induced by LMP1, and previous studies have suggested that expression of TRAF1 is higher in EBV-associated tumors than in their EBV-negative counterparts. To determine whether this was the case in posttransplant lymphoproliferative disease (PTLD) and related disorders, we used immunohistochemistry to analyze expression of TRAF1 in a total of 42 such lesions arising in a variety of immunosuppressive states. The specimens consisted of 22 PTLD lesions, 18 acquired immunodeficiency syndrome-associated lymphomas, including 6 primary central nervous system lymphomas, and 2 cases of Hodgkin disease. The presence of latent EBV infection was determined by EBER in situ hybridization, and expression of EBV-LMP1 was detected by immunohistochemistry. Latent EBV infection, as determined by a positive EBER signal, was detected in 36 of 42 tumors. Of the EBER-positive specimens, 30 of 36 also expressed LMP1. Twenty-four of 30 LMP1-positive tumors, including both Hodgkin disease specimens, expressed TRAF1, compared with only 3 of 12 LMP1-negative tumors. This difference was statistically significant (P <.005). These results show frequent expression of TRAF1 at the protein level in LMP1-positive PTLD and related disorders and suggest an important role for LMP1-mediated TRAF1 signaling in the pathogenesis of EBV-positive tumors arising in immunosuppressive states.

Cognitive development: children's knowledge about the mind.

This chapter reviews theory and research on the development of children's knowledge about the mental world, focusing especially on work done during the past 15 years under the rubric of theory-of-mind development. The three principal approaches to explaining this development--theory theory, modular theory, and simulation theory--are described first. Next comes a description of infant precursors or protoforms of theory-of-mind knowledge in infancy, including a beginning awareness of the intentionality and goal-directedness of human actions. This discussion is followed by a summary of the postinfancy development of children's understanding of visual perception, attention, desires, emotions, intentions, beliefs, knowledge, pretense, and thinking. Briefly considered next are intracultural, intercultural, and interspecies differences in theory-of-mind development. The chapter then concludes with some guesses about the future of the field.

The development of knowledge about visual perception.

This chapter describes recent theory and research in one limited area of social-cognitive development, namely, the childhood acquisition of knowledge about visual perception. The author and his co-workers have hypothesized that there are two developmental levels of such knowledge. At earlier-developing Level 1, the child understands that others as well as the self see objects, and is also able to infer correctly what objects they do or do not currently see if provided with adequate cues. At later-developing Level 2, the child understands not only that people can see objects, but also that they can have differing visual experiences while seeing the same object; most notably, they can have different spatial perspectival views of it when looking at it from different positions. Arguments and evidence for the developmental distinction between Level 1 and Level 2 knowledge are briefly presented in Section I. A more detailed model of Level 1 knowledge is presented in Section II, together with an account of several studies of its development during the first four years of life. During these early years, children appear to learn a great deal about how to produce visual percepts in others (showing and pointing to things), how to deprive others of percepts (hide objects), and how to diagnose the percepts they currently have (follow others' direction of gaze and pointing gestures). Section III similarly reviews recent theory and research on the development of Level 2 perspective-taking knowledge in older children. This work is focused mainly on the acquisition and use of very general perspective-taking rules, such as the rule that two observers who look at an object array from the same spatial position must on that account necessarily have identical perspectival views of the array. Section IV described further developmental research that could be or is being done on Level 2 knowledge, Level 1 knowledge, and on the Level 1-Level 2 distinction.

Young children's understanding of "remember" and "forget".

3 studies examined young children's understanding that if one "remembers" or "forgot," one must have known at a prior time. In Study 1, 4-year-olds but not 3-year-olds understood the prior knowledge component of "forgot"; both groups understood that a character with prior knowledge was "gonna remember." Study 2 controlled for the possibility that good performance on "remember" might be due to a simple association of remembering with knowledge. A significant number of 4-year-olds but not 3-year-olds understood that when 2 characters currently knew, the one with prior knowledge remembered, and that when neither character currently knew, the one with prior knowledge forgot. Study 3 made prior knowledge more salient by making the remembered or forgotten item visible to the subjects throughout. 4-year-olds performed near ceiling on both verbs, whereas 3-year-olds' performance did not differ from chance. The results are discussed in relation to children's developing understanding of the mind.

Young children's knowledge about visual perception: projective size and shape.

Although recent research indicates that an increased sensitivity to visual appearances develops around 4 or 5 years of age, evidence from perceptual studies suggests that certain types of appearances, that is, projective size and shape, are not noticed or understood until at least 7. 4 experiments investigated preschool children's knowledge of the projective size--distance and projective shape--orientation relationships. In Experiment 1, 3- and 4-year-olds were asked whether an object should be moved farther or nearer in order to increase or decrease its apparent size. 4-year-olds performed significantly better than chance, but 3-year-olds did not. Experiment 2 showed that 3-year-olds are able to perceive projective size changes, indicating that although they do not fully understand the projective size-distance relationship, the necessary perceptual information is potentially available to them. In Experiment 3, 3- and 4-year-olds were asked to indicate how a circular object should be rotated to make it appear either circular or elliptical. Again, 4-year-olds performed significantly better than chance, but 3-year-olds did not. Again also, the results of Experiment 4 indicate that although 3-year-olds are not aware of the projective shape-orientation relationship, they are capable of attending to changes in projective shape. Thus, the constraints on children's knowledge of the projective size-distance and projective shape-orientation relationships seem to be at least partly cognitive rather than wholly perceptual. These results are interpreted as further evidence for the acquisition of level 2 percept knowledge during early childhood.

Young children's understanding of forgetting over time.

2 studies investigated young children's understanding that as the retention interval increases, so do the chances that one will forget. In Study 1 (24 3-year-olds and 24 4-year-olds), 4-year-olds but not 3-year-olds understood that of 2 characters who simultaneously saw an object, the character who waited longer before attempting to find it would not remember where it was. In study 2 (24 3-year-olds and 24 4-year-olds), 4-year-olds but not 3-year-olds understood that of 2 objects seen by a character, the object that was seen a "long long time ago" would be forgotten and the object seen "a little while ago" would be remembered. The findings are discussed in relation to research on young children's understanding of the acquisition, retention, and retrieval of knowledge over time.

Seeing and believing: children's understanding of the distinction between appearance and reality.

When young children are asked questions about objects with misleading appearances, they make two kinds of errors: (1) phenomenism--they report appearance when asked to report reality; and (2) intellectual realism--they report reality when asked to report appearance. Two studies with 3-year-old children tested the hypothesis that phenomenism errors predominate when children are asked about objects' real and apparent properties, whereas intellectual realism errors predominate when children are asked about objects' real and apparent identities. The results of these studies provided some support for the property-identity hypothesis; children's appearance-reality judgments about properties tended to differ from those about identities. More phenomenism errors were elicited when the stimuli were described to the children in terms of their properties than when the very same stimulus objects were described in terms of their identities. Identity tasks were not found to elicit predominantly intellectual realism errors, although the data showed trends in this direction. The implications of these results for theories about young children's tendency to accept things in terms of their perceptual characteristics were briefly discussed.

Development of knowledge about communication: children's evaluations of explicitly ambiguous messages.

Kindergartners and second graders evaluated the communicative clarity of brief oral instructions under 3 conditions: (1) unambiguous: referentially unambiguous instructions that the subjects saw a puppet listener correctly carry out; (2) no closure: ambiguous instructions that the puppet explicitly identified as ambiguous and refused to try to carry out; (3) closure: equally ambiguous instructions that the puppet also explicitly identified as ambiguous but nonetheless carried out, confidently asserting that he thought the speaker meant a specific 1 of the 2 equally possible referents. The younger, but not the older, subjects were influenced by the listener's behavior as well as by the speaker's: That is, they rated the closure instructions as clearer than the no-closure instructions, although less clear than the unambiguous ones. These results suggest that the growth of children's knowledge about communication includes the developing awareness that, in communication situations like the above, an ambiguous message is intrinsically unclear and remains a poor message regardless of the listener's response to it.

Young children's preference for mental state versus behavioral descriptions of human action.

Young children have traditionally been conceived of as little behaviorists who focus on the external and lack knowledge of internal states. In contrast, some recent research suggests that they do have a fundamentally correct understanding of mental life. Children may often focus on the external, not because they are unaware of the internal but because in test situations the external has been more cognitively available to them. Our studies asked whether 3-year-olds prefer to describe human action in behavioral terms when a mental state description is made equally available and salient. 3-year-olds were presented with 3 differently colored photocopies of the same picture. The first copy was described with reference to the mental state of the person in the picture, and the second copy was described with reference to the person's behavior, or vice versa. Then the third copy was presented, and the child was asked to tell a puppet about this picture--effectively, to choose between the mental state description and the behavioral description. In each of 2 studies, 20 3-year-olds made 12 such choices. In both studies, children tended to choose mentalistic descriptions significantly more often than behavioral ones, even when there was better pictorial support for the behavioral ones. These findings suggest that, given equally available options, young children may prefer to describe people in terms of their mental states rather than their behaviors.

Inferring false beliefs from actions and reactions.

Current evidence suggests that young children have little understanding of false belief. Standard false belief tasks, however, may underestimate children's ability for 2 reasons. First, the only cue to belief in these tasks is a protagonist's lack of perceptual access to some critical event, and this may not be a very salient cue for young children. Second, the standard tasks require children to make forward-looking predictions from the causes of a belief (e.g., from what a protagonist has or has not perceived) to either the protagonist's belief or the protagonist's action, and children may not be very skilled at making such predictions. In 2 experiments we investigated whether 3-year-olds would do better on tasks in which the belief cues were stronger, and in which they could reason backward to the belief from its effects (e.g., from a protagonist's actions and reactions). Even on these easy tasks, however, they did not perform well. These findings provide strong support for the view that children of this age do not fully understand the representational nature of belief.

Understanding and remembering: children's knowledge about the differential effects of strategy and task variables on comprehension and memorization.

Developmental changes in knowledge about the differences between the mental processes of comprehension and memory were investigated in 3 studies using first graders, third graders, and undergraduates as subjects. 2 types of knowledge were assessed: (a) knowledge about the types of strategies appropriate to achieving the goals of comprehension, memorization, or a combination of the 2; (b) knowledge about how different task variables differentially affect comprehension and memorization tasks. With respect to the former, only the 2 older groups showed some understanding of the differential effectiveness of rehearsal and word familiarity for memory versus comprehension and thus showed some understanding of the comprehension-memory distinction with respect to strategy knowledge. As for the latter, only undergraduates correctly differentiated between the 2 mental processes with respect to the task variables of list length, item familiarity, and the categorical organization of the items.

Development of the ability to distinguish communicative intention and literal message meaning.

Children's ability to distinguish the literal meaning of a message and the speaker's communicative intent was investigated in 2 experiments. First- and second-grade children evaluated brief referential communication messages for ambiguity under 2 conditions. In an informed condition, the children knew which referent the speaker had intended. In an uninformed condition, they did not know the intended referent. 2 communication systems were used. In Experiment 1, the messages were written on cards and read to the child; in Experiment 2, a novel communication system was used. The developmental pattern of results was similar for both studies. The results showed that the first graders in the informed condition often claimed that an ambiguous message could not refer to a referent the speaker had not meant, whereas children in the uninformed condition were able to detect the referential ambiguity of the message. There were no condition differences for the second graders. The results suggest that young children's ability to analyze the literal meaning of a message is affected by the accessibility of the speaker's communicative intent and that children may develop a general ability to analyze representations of communicative intention.

Intellectual realism: the role of children's interpretations of pictures and perceptual verbs.

Intellectual realism refers to the tendency of young children to indicate incorrectly all that is present in an object array when asked to indicate only what they can see of it from a particular perspective. 3 experiments tested and confirmed the hypotheses that children's interpretation of (a) pictorial conventions and of (b) the expression "look like" may increase this tendency. The results of this and other studies suggest that young children's difficulties with adult pictorial conventions, with the wording of task instructions, and with the concept of a momentary, view-determined appearance can all lead to intellectual realism errors.

Development of knowledge about the appearance-reality distinction.

7 studies of the acquisition of knowledge about the appearance-reality distinction suggest the following course of development. Many 3-year-olds seem to possess little or no understanding of the distinction. They fail the simplest Appearance-Reality (AR) tasks and are unresponsive to efforts to teach them the distinction. Skill in solving simple AR tasks is highly correlated with skill in solving simple perceptual Perspective-taking (PT) tasks; this suggests the hypothesis that the ability to represent the selfsame stimulus in two different, seemingly incompatible ways may underlie both skills. Children of 6-7 years have acquired both skills but nevertheless find it very difficult to reflect on and talk about such appearance-reality concepts as "looks like," "really and truly," and "looks different from the way it really and truly is." In contrast, children of 11-12 years, and to an even greater degree college students, possess a substantial body of rich, readily accessible, and explicit knowledge in this area.

Children's understanding of the stream of consciousness.

Children and adults were tested for their understanding that there is a virtually continuous flow of mental content in a waking person, a "stream of consciousness" that continues to run even when the person is not examining stimuli perceptually or trying to solve a problem. There was a marked increase with age from preschool to adulthood in subjects' tendency to say that a person who was just waiting quietly was having "some thoughts and ideas" rather than "a mind empty of thoughts and ideas." 4-year-olds also tended to say that the mind of a waiting person was "not doing anything," whether that person was another individual or themselves, and that a person who wanted to could keep his or her "mind completely empty of all thoughts and ideas" for 3 min. These results suggest that preschoolers' conceptions of people's mental lives may be quite different from those of older children and adults.

Young children's ability to differentiate appearance-reality and level 2 perspectives in the tactile modality.

A key acquisition in the child's developing knowledge of the mind is the subjective-objective distinction, which includes a clear understanding that things may appear to be other than the way they really are (appearance-reality distinction) and may present different appearances to self and others (Level 2 perspective-taking). Previous studies using tasks involving visual appearances have found that most children do not show such understanding until 4 or 5 years of age. However, a conceptual analysis of tactile as compared to visual and other perceptual experiences suggested the hypothesis that this understanding might appear earlier if the appearances the child must identify are tactile rather than visual. This hypothesis was supported by the results of 3 studies. In Studies 1 and 2, 3-year-old subjects could correctly indicate, for example, that an ice cube they were feeling with a heavily gloved finger did not feel cold to that finger (tactile appearance for the self), did feel cold to the experimenter's ungloved or thinly gloved finger (tactile appearance for another person), and was a cold ice cube, really and truly (reality). In contrast, and consistent with previous research findings, they were much poorer at distinguishing between real and visually apparent object identity, number, and color. Similarly, in Study 3 they tended to perform better on tactile appearance-reality tasks involving the properties of number, wetness, and intactness than on visual appearance-reality tasks that involved these same properties.