Simulated Contact and Attitudes Toward Autistic Adults: Effects of Gender of the Autistic Adult and Mediation by Intergroup Anxiety.

PURPOSE: Neurotypical peers tend to have negative attitudes toward autistic peers, which may contribute to negative outcomes for autistic individuals. The present study was designed to build upon previous findings by testing whether simulating contact with an individual labeled as autistic and exhibiting stereotypical autistic behaviors, which has been shown to improve neurotypical individuals' attitudes toward autistic peers, depended on the gender of the imagined person. We also examined whether intergroup anxiety mediated the effects of simulated contact on these attitudes. METHODS: Neurotypical undergraduate participants (n = 194) were assigned to simulated contact scenarios in which the person in the imagined contact situation was labeled as autistic or not, exhibited stereotypical autistic behaviors or not and was given a female-identifying or male-identifying name. Participants completed questionnaires that assessed their attitudes toward autism, their previous contact with autistic individuals and their intergroup anxiety with future interactions with autistic people. RESULTS: As expected, after imagining contact with a person exhibiting stereotypical autistic behaviors, attitudes toward autistic individuals were more positive following interactions with male- but not female-identifying autistic partners. Intergroup anxiety was found to be a mediator of the effects of imagined contact on attitudes toward autistic individuals. CONCLUSION: These findings lend further support for imagined contact as a method to improve attitudes toward autistic individuals, identify intergroup anxiety as a mediator and begin to demonstrate some situations, such as imagining a female-identifying autistic individual, where imagined contact may not be effective in changing attitudes.

The Impact of an Autistic Character Media Portrayal on Autistic Stereotypes : MEDIA PORTRAYAL.

PURPOSE: Research has demonstrated that neurotypical college students view their autistic peers more negatively than their neurotypical peers and endorse stereotypes related to autism. One way to improve attitudes towards autistic individuals is to induce vicarious intergroup contact through the media in which seeing the lived experiences of an autistic character may reduce stereotypes via social learning. The current study sought to examine whether exposure to an autistic character in a television show would impact the stereotypes that neurotypical college students have about autism. METHODS: College student participants (n = 147) viewed one of three short video clips depicting an autistic character who spoke about her experiences with ASD (i.e., informational condition), behaved in a relatable manner to neurotypical students (i.e., relatable condition), or engaged in stereotypical autistic behaviors (i.e., stereotypical condition). RESULTS: Results indicated that stereotypes about autistic people were less negative for participants who watched the informational clip than the relatable clip, and liking for the character mediated this relationship. CONCLUSION: Our findings suggest that a short video featuring a likeable autistic person may reduce stereotypes about autism.

Dual orexin/hypocretin receptor antagonism attenuates NMDA receptor hypofunction-induced attentional impairments in a rat model of schizophrenia.

Schizophrenia is a neuropsychiatric condition that is associated with impaired attentional processing and performance. Failure to support increasing attentional load may result, in part, from inhibitory failure in attention-relevant cortical regions, and available antipsychotics often fail to address this issue. Orexin/hypocretin receptors are found throughout the brain and are expressed on neurons relevant to both attention and schizophrenia, highlighting them as a potential target to treat schizophrenia-associated attentional dysfunction. In the present experiment, rats (N = 14) trained in a visual sustained attention task that required discrimination of trials which presented a visual signal from trials during which no signal was presented. Once trained, rats were then co-administered the psychotomimetic N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801: 0 or 0.1 mg/kg, intraperitoneal injections) and the dual orexin receptor antagonist filorexant (MK-6096: 0, 0.1, or 1 mM, intracerebroventricular infusions) prior to task performance across six sessions. Dizocilpine impaired overall accuracy during signal trials, slowed reaction times for correctly-responded trials, and increased the number of omitted trials throughout the task. Dizocilpine-induced increases in signal trial deficits, correct response latencies, and errors of omission were reduced following infusions of the 0.1 mM, but not 1 mM, dose of filorexant. As such, orexin receptor blockade may improve attentional deficits in a state of NMDA receptor hypofunction.

Orexin A, an amphipathic α-helical neuropeptide involved in pleiotropic functions in the nervous and immune systems: Synthetic approach and biophysical studies of the membrane-bound state.

This research reports on the membrane interactions of orexin A (OXA), an α-helical and amphipathic neuropeptide that contains 33 residues and two disulfide bonds in the N-terminal region. OXA, which activates the orexins 1 and 2 receptors in neural and immune cell membranes, has essential pleiotropic physiological effects, including at the levels of arousal, sleep/wakefulness, energy balance, neuroprotection, lipid signaling, the inflammatory response, and pain. As a result, the orexin system has become a prominent target to treat diseases such as sleep disorders, drug addiction, and inflammation. While the high-resolution structure of OXA has been investigated in water and bound to micelles, there is a lack of information about its conformation bound to phospholipid membranes and its receptors. NMR is a powerful method to investigate peptide structures in a membrane environment. To facilitate the NMR structural studies of OXA exposed to membranes, we present a novel synthetic scheme, leading to the production of isotopically-labeled material at high purity. A receptor activation assay shows that the 15N-labeled peptide is biologically active. Biophysical studies are performed using surface plasmon resonance, circular dichroism, and NMR to investigate the interactions of OXA with phospholipid bilayers. The results demonstrate a strong interaction between the peptide and phospholipids, an increase in α-helical content upon membrane binding, and an in-plane orientation of the C-terminal region critical to function. This new knowledge about structure-activity relationships in OXA could inspire the design of novel therapeutics that leverage the anti-inflammatory and neuro-protective functions of OXA, and therefore could help address neuroinflammation, a major issue associated with neurological disorders such as Alzheimer's disease.

Dual orexin/hypocretin receptor antagonism attenuates attentional impairments in an NMDA receptor hypofunction model of schizophrenia.

Schizophrenia is a neuropsychiatric condition that is associated with impaired attentional processing and performance. Failure to support increasing attentional load may result, in part, from abnormally overactive basal forebrain projections to the prefrontal cortex, and available antipsychotics often fail to address this issue. Orexin/hypocretin receptors are expressed on corticopetal cholinergic neurons, and their blockade has been shown to decrease the activity of cortical basal forebrain outputs and prefrontal cortical cholinergic neurotransmission. In the present experiment, rats (N = 14) trained in a visual sustained attention task that required discrimination of trials which presented a visual signal from trials during which no signal was presented. Once trained, rats were then co-administered the psychotomimetic N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801: 0 or 0.1 mg/kg, intraperitoneal injections) and the dual orexin receptor antagonist filorexant (MK-6096: 0, 0.1, or 1 mM, intracerebroventricular infusions) prior to task performance across six sessions. Dizocilpine impaired overall accuracy during signal trials, slowed reaction times for correctly-responded trials, and increased the number of omitted trials throughout the task. Dizocilpine-induced increases in signal trial deficits, correct response latencies, and errors of omission were reduced following infusions of the 0.1 mM, but not 1 mM, dose of filorexant. Orexin receptor blockade, perhaps through anticholinergic mechanisms, may improve attentional deficits in a state of NMDA receptor hypofunction. Highlights: Schizophrenia is associated with attentional deficits that may stem from abnormally reactive BF projections to the prefrontal cortexOrexin receptor antagonists decrease acetylcholine release and reduce prefrontal cortical activityThe dual orexin receptor antagonist filorexant alleviated impairments of attention following NMDA receptor blockade.

Role of the locus coeruleus and basal forebrain in arousal and attention.

Experimental evidence has implicated multiple neurotransmitter systems in either the direct or indirect modulation of cortical arousal and attention circuitry. In this review, we selectively focus on three such systems: 1) norepinephrine (NE)-containing neurons of the locus coeruleus (LC), 2) acetylcholine (ACh)-containing neurons of the basal forebrain (BF), and 3) parvalbumin (PV)-containing gamma-aminobutyric acid neurons of the BF. Whereas BF-PV neurons serve as a rapid and transient arousal system, LC-NE and BF-ACh neuromodulation are typically activated on slower but longer-lasting timescales. Recent findings suggest that the BF-PV system serves to rapidly respond to even subtle sensory stimuli with a microarousal. We posit that salient sensory stimuli, such as those that are threatening or predict the need for a response, will quickly activate the BF-PV system and subsequently activate both the BF-ACh and LC-NE systems if the circumstances require longer periods of arousal and vigilance. We suggest that NE and ACh have overlapping psychological functions with the main difference being the precise internal/environmental sensory situations/contexts that recruit each neurotransmitter system - a goal for future research to determine. Implications of dysfunction of each of these three attentional systems for our understanding of neuropsychiatric conditions are considered. Finally, the contemporary availability of research tools to selectively manipulate and measure the activity of these distinctive neuronal populations promises to answer longstanding questions, such as how various arousal systems influence downstream decision-making and motor responding.

The Effects of Contact and Labeling on Attitudes Towards Individuals with Autism.

Typically developing young adults perceive their peers with autism more negatively than those without autism, but less so when they have experience with individuals with autism. Study 1 examined whether typically developing university students' (n = 70) judgments of their peers would differ as a function of interpersonal contact and being labeled as autistic. Perceptions of peers with autism were consistent with stereotypes about autism and were associated with contact. In Study 2, typically developing university students (n = 130) imagined interacting with a student with manipulations of perseverative behavior and the label of autism. Attitudes towards individuals with autism were more positive following an imagined contact scenario with a peer demonstrating perseverative behavior with a label of autism.

Assessment of Sesame Street online autism resources: Impacts on parental implicit and explicit attitudes toward children with autism.

The current study sought to characterize implicit bias toward children with autism and examine whether viewing educational materials about autism would change attitudes toward children with autism. A website developed by Sesame Street containing information about autism and resources for families was distributed to parents of children with autism (n = 473) and parents of children without autism (n = 707). Pre- and post-test measures of implicit bias toward children with autism; explicit attitudes and knowledge about autism; and parenting confidence, strain, and stigma were completed before and after the website was presented. Results indicated that parents of children with autism showed less implicit bias compared with those of non-autistic children during the pre-test, but the groups did not differ at the post-test. Parents without autistic children and those with more negative explicit attitudes showed a greater reduction in implicit bias from the pre- to the post-test. In addition, for parents of children with autism, a more positive change in explicit attitudes and increased knowledge from the pre- to the post-test was associated with more empowerment at the post-test. Together, our findings suggest that the online educational resources can reduce implicit bias against children with autism and help mitigate some of the psychological issues associated with parenting children with autism.

Implicit and Explicit Attitudes Toward Autistic Adults.

Background: Research examining attitudes toward autistic adults has relied on explicit self-report measures, which may be susceptible to socially desirable responding. Because implicit attitudes predict behavioral rejection, understanding both implicit and explicit attitudes toward autistic adults is important. Furthermore, previous research has almost exclusively examined attitudes toward autistic children and has not investigated attitudes toward autistic adults who may also experience prejudice from their peers. Methods: We created an implicit association test (IAT) to examine implicit attitudes toward autistic adults. In Study 1, we examined 94 neurotypical adults' (mean [M]age = 31.37 years) implicit attitudes and explicit attitudes toward autistic adults as well as autistic behaviors. In Study 2 (n = 137; M age = 33.43 years), we assessed the same variables using an IAT with descriptive rather than stereotypical words. Results: Participants from both studies demonstrated negative implicit attitudes but positive explicit attitudes toward autistic adults. In Study 2, analyses examining self-reported traits related to autism revealed that more autistic behaviors were associated with less implicit bias. Conclusions: These findings may help explain why autistic adults report discrimination from their peers. The results suggest that there may be benefits in modifying interventions that reduce implicit bias toward other marginalized groups for use with implicit bias against autistic adults. Lay summary: Why was this study done?: The goal of this study was to understand how neurotypical adults in the United States feel and think about autistic adults. Negative attitudes can lead to discrimination against autistic adults or to harmful interactions between autistic and neurotypical adults. Although research has previously examined the attitudes that neurotypical adults have toward autistic adults, most of this work has directly asked people about their attitudes, assessing their explicit, or conscious, attitudes. Neurotypical adults, however, may not be able or willing to admit that they have negative attitudes toward autistic adults. Therefore, it is important to evaluate implicit attitudes, which are underlying attitudes at the unconscious level of awareness.What was the purpose of this study?: This study investigated the implicit and explicit attitudes that neurotypical adults in the general U.S. population have about autistic adults. Assessing both kinds of attitudes is important because each type of attitude predicts different sorts of behaviors toward and judgments of individuals.What did the researchers do?: We conducted this study online using a crowdsourcing method of data collection (Amazon's Mechanical Turk) that gave us access to adults throughout the United States. We developed and administered a reaction-time task to examine implicit attitudes toward autistic adults. In this task, participants rapidly categorized words associated with autism and words not associated with autism as being "good" or "bad." We assessed explicit attitudes with questions about people's knowledge of autism and their liking for autistic adults. Study 1 measured 94 neurotypical adults' (average age = 31.37 years) implicit and explicit attitudes toward autistic adults; Study 2 measured 137 neurotypical adults' (average age = 33.43 years) implicit and explicit attitudes. Whereas Study 1's implicit task used words associated with stereotypes about autistic adults (e.g., extraverted, independent), Study 2 used nonstereotypical words associated with autism (e.g., autistic, spectrum).What were the results of the studies?: Participants in both studies reported positive explicit attitudes but negative implicit attitudes toward autistic adults. In one study, we also found that neurotypical adults with more autistic traits themselves had more positive implicit attitudes toward autistic adults.What do these findings add to what was already known?: Although previous research examined neurotypical adults' explicit attitudes toward autistic adults, the current study demonstrated that neurotypical adults hold negative implicit attitudes toward autistic adults. These findings may help explain why autistic adults experience discrimination from neurotypical adults. Furthermore, our findings suggest that having more autistic traits can lead to a better understanding of the behaviors associated with autism.What are the potential weaknesses in the study?: Limitations of the study were that we collected the data online rather than in person and we only included neurotypical adults as participants.How will these findings help autistic adults now or in the future?: These results shed light on underlying reasons for the potential negative judgments and discrimination that autistic adults face from neurotypical adults. These findings should encourage policy makers to design and implement training programs to reduce neurotypical adults' negative attitudes toward autistic adults.

Neuropharmacology of attention.

Early philosophers and psychologists defined and began to describe attention. Beginning in the 1950's, numerous models of attention were developed. This corresponded with an increased understanding of pharmacological approaches to manipulate neurotransmitter systems. The present review focuses on the knowledge that has been gained about these neurotransmitter systems with respect to attentional processing, with emphasis on the functions mediated within the medial prefrontal cortex. Additionally, the use of pharmacotherapies to treat psychiatric conditions characterized by attentional dysfunction are discussed. Future directions include developing a more comprehensive understanding of the neural mechanisms underlying attentional processing and novel pharmacotherapeutic targets for conditions characterized by aberrant attentional processing.

Autistic traits and social anxiety predict differential performance on social cognitive tasks in typically developing young adults.

The current work examined the unique contribution that autistic traits and social anxiety have on tasks examining attention and emotion processing. In Study 1, 119 typically-developing college students completed a flanker task assessing the control of attention to target faces and away from distracting faces during emotion identification. In Study 2, 208 typically-developing college students performed a visual search task which required identification of whether a series of 8 or 16 emotional faces depicted the same or different emotions. Participants with more self-reported autistic traits performed more slowly on the flanker task in Study 1 than those with fewer autistic traits when stimuli depicted complex emotions. In Study 2, participants higher in social anxiety performed less accurately on trials showing all complex faces; participants with autistic traits showed no differences. These studies suggest that traits related to autism and to social anxiety differentially impact social cognitive processing.

Adolescent transitions in reflexive and non-reflexive behavior: Review of fear conditioning and impulse control in rodent models.

Adolescence is a time of critical brain changes that pave the way for adult learning processes. However, the extent to which learning in adolescence is best characterized as a transitional linear progression from childhood to adulthood, or represents a period that differs from earlier and later developmental stages, remains unclear. Here we examine behavioral literature on associative fear conditioning and complex choice behavior with rodent models. Many aspects of fear conditioning are intact by adolescence and do not differ from adult patterns. Sufficient evidence, however, suggests that adolescent learning cannot be characterized simply as an immature precursor to adulthood. Across different paradigms assessing choice behavior, literature suggests that adolescent animals typically display more impulsive patterns of responding compared to adults. The extent to which the development of basic conditioning processes serves as a scaffold for later adult decision making is an additional research area that is important for theory, but also has widespread applications for numerous psychological conditions.

Promoting Cognitive Flexibility Under Attention-demanding Conditions in Aged Rats.

BACKGROUND: Age-related decline in cognitive flexibility and learning contributes to poorer quality of life. Thus, it is important to develop procedures that minimize age-related cognitive decline. Previous research has shown that, when young adult rats were trained in an attention-demanding task with a distracter, they learned a new task more quickly compared with rats trained in the same attention- demanding task without a distracter. OBJECTIVE: The goal of the present experiment was to test whether this beneficial effect of distracter exposure was observed in aged rats. METHOD: Male FBNF hybrid rats (n=20) trained in a two-lever visual sustained attention task that required discrimination of brief illumination of a centrally located panel light compared with trials when the light was not illuminated. At age 20 months, half of the animals received a flashing houselight distracter for the remaining testing sessions and the other animals did not. After 20 sessions, new task trials were interspersed within the sessions, when the rats received water access for pressing the lever under the left or right panel light after that light was illuminated. RESULTS: When 70% of the trials in a session were the new discrimination task, the distracter-exposed animals had higher accuracy in detecting the shortest signal in the remaining attention task trials compared with rats not exposed to the distracter. CONCLUSION: The present results suggest that aged animals' learning can benefit from overcoming distracter exposure, although not to the same extent as younger animals.

Orexin A-induced enhancement of attentional processing in rats: role of basal forebrain neurons.

RATIONALE: Orexins are neuropeptides released in multiple brain regions from neurons that originate within the lateral hypothalamus and contiguous perfornical area. The basal forebrain, a structure implicated in attentional processing, receives orexinergic inputs. Our previous work demonstrated that administration of an orexin-1 receptor antagonist, SB-334867, systemically or via infusion directly into the basal forebrain, can disrupt performance in a task that places explicit demands on attentional processing. OBJECTIVES: Given that the orexin-1 receptor binds orexin A with high affinity, we tested whether orexin A could enhance attention in rats. METHODS: Attentional performance was assessed using a task that required discrimination of variable duration visual signals from trials when no signal was presented. We also tested whether infusions of orexin A into the lateral ventricle could attenuate deficits following lesions of medial prefrontal cortical cholinergic projections that arise from the basal forebrain. RESULTS: Infusions of orexin A into the basal forebrain attenuated distracter-induced decreases in attentional performance. Orexin A attenuated deficits in lesioned animals when a visual distracter was presented. CONCLUSION: The present results support the view that orexin A can enhance attentional performance via actions in the basal forebrain and may be beneficial for some conditions characterized by attentional dysfunction due to disruption of cortical cholinergic inputs.

Repeated visual distracter exposure enhances new discrimination learning and sustained attention task performance in rats.

Repeated exposure to distraction requires attentional effort to restore task performance. However, the impact of repeated distracter exposure and exertion of attentional effort on new learning has not been examined. In the present experiment, rats were trained in a two-lever sustained attention task. Rats then continued to train, for 12 sessions, in this task either with or without a flashing houselight distracter throughout the session. The flashing houselight transiently decreased attentional performance. Trials that were part of a new light-location discrimination task were then interspersed within the sustained attention task sessions. The frequency of these new light-location discrimination trials increased with additional training. Rats exposed to the distracter exhibited higher accuracy levels during some blocks of sessions in the new light-location discrimination task trials and in the remaining sustained attention task trials compared to rats that were not exposed to the distracter. The effects of repeated distracter exposure are interpreted in the context of an "occasion-setting" model that has been used to describe performance in this task.

Task demands dissociate the effects of muscarinic M1 receptor blockade and protein kinase C inhibition on attentional performance in rats.

The cholinergic system is known to be necessary for normal attentional processing. However, the receptors and mechanisms mediating the effects of acetylcholine on attention remain unclear. Previous work in our laboratory suggested that cholinergic muscarinic receptors are critical for maintaining performance in an attention-demanding task in rats. We examined the role of the muscarinic M(1) receptor and protein kinase C (PKC), which is activated by the M(1) receptor, in attention task performance. Rats were trained in an attention-demanding task requiring discrimination of brief (500, 100, 25 ms) visual signals from trials with no signal presentation. The effects of muscarinic M(1) receptor blockade were assessed by administering dicyclomine (0-5.0 mg/kg). The effects of PKC inhibition were assessed by administering chelerythrine chloride (0-2.0 mg/kg). Dicyclomine decreased the accuracy of detecting longer signals in this attention task, including when attentional demands were increased by flashing a houselight throughout the session. Chelerythrine chloride decreased the accuracy of signal detection in the standard version of the task but not when the houselight was flashed throughout the session. The present findings indicate that muscarinic M(1) receptors are critical for maintaining performance when attentional demands are increased, and that PKC activity may contribute to some aspects of attentional performance.

Adolescent nicotine exposure disrupts context conditioning in adulthood in rats.

Despite the prevalence of smoking among adolescents, few studies have assessed the effects of adolescent nicotine exposure on learning in adulthood. In particular, it remains unclear whether adolescent nicotine exposure has effects on hippocampus-dependent learning that persist into adulthood. The present experiment examined whether there were effects of adolescent nicotine exposure on context conditioning, a form of learning dependent on the integrity of the hippocampus, when tested during adulthood. Rats were exposed to nicotine during adolescence (postnatal days [PD] 28-42) via osmotic minipump (0, 3.0 or 6.0mg/kg/day). Context conditioning occurred in early adulthood (PD 65-70). Animals were exposed to an experimental context and were given 10 unsignaled footshocks or no shock. Additional groups were included to test the effects of adolescent nicotine on delay conditioning, a form of learning that is not dependent upon the hippocampus. Conditioning was assessed using a lick suppression paradigm. For animals in the context conditioning groups, adolescent nicotine resulted in significantly less suppression of drinking in the presence of context cues compared with vehicle-pretreated animals. For animals in the delay conditioning groups, there was a trend for adolescent nicotine (3.0mg/kg/day) to suppress drinking compared to vehicle-pretreated animals. There were no differences in extinction of contextual fear or cued fear between rats previously exposed to vehicle or nicotine. The data indicate that adolescent nicotine administration impairs context conditioning when animals are trained and tested as adults. The present data suggest that adolescent nicotine exposure may disrupt hippocampus-dependent learning when animals are tested during adulthood.

Systemic and intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, disrupts attentional performance in rats.

RATIONALE: Orexin neurons project to a number of brain regions, including onto basal forebrain cholinergic neurons. Basal forebrain corticopetal cholinergic neurons are known to be necessary for normal attentional performance. Thus, the orexin system may contribute to attentional processing. OBJECTIVES: We tested whether blockade of orexin-1 receptors would disrupt attentional performance. METHODS: Rats were trained in a two-lever sustained attention task that required discrimination of a visual signal (500, 100, 25 ms) from trials with no signal presentation. Rats received systemic or intrabasalis administration of the orexin-1 receptor antagonist, SB-334867, prior to task performance. RESULTS: Systemic administration of the orexin-1 receptor antagonist, SB-334867 (5.0 mg/kg), decreased detection of the longest duration signal. Intrabasalis SB-334867 (0.60 microg) decreased overall accuracy on trials with longer signal durations. CONCLUSIONS: These findings suggest that orexins contribute to attentional processing, although neural circuits outside of basal forebrain corticopetal cholinergic neurons may mediate some of these effects.

Attentional demands for demonstrating deficits following intrabasalis infusions of 192 IgG-saporin.

Previous research has shown that basal forebrain cholinergic inputs to the cerebral cortex are necessary for attentional processing. However, the key components of attention-demanding tasks for demonstrating deficits following loss of basal forebrain corticopetal cholinergic neurons are unclear. In the present experiment, rats were trained in a visual cued discrimination task with limited explicit attentional demands and then received intrabasalis infusions of the immunotoxin, 192 IgG-saporin, or saline. Postsurgically, attentional demands were increased by decreasing the signal duration or the intertrial interval or by increasing the variability of these parameters. Subsequently, rats were trained in a task that required discrimination of successively presented signals and "blank" trials with no signal presentation. Again, attentional demands were increased by manipulating signal duration or the intertrial interval. Finally, all rats were trained in a task with both the signal duration and the intertrial interval designed to increase attentional demands. Compared to sham-lesioned animals, lesioned animals exhibited deficits in signal detection only during the successive discrimination task with both the signal duration and intertrial interval shorter and variable. The present data suggest that attentional deficits following loss of cortical cholinergic inputs result from overall attentional task demands rather than being dependent on any single task parameter.