James P. Morris

Grasping the Intentions of Others: The Perceived Intentionality of an Action Influences Activity in the Superior Temporal Sulcus during Social Perception

An explication of the neural substrates for social perception is an important component in the emerging field of social cognitive neuroscience and is relevant to the field of cognitive neuroscience as a whole. Prior studies from our laboratory have demonstrated that passive viewing of biological motion (Pelphrey, Mitchell, et al., 2003; Puce et al., 1998) activates the posterior superior temporal sulcus (STS) region. Furthermore, recent evidence has shown that the perceived context of observed gaze shifts (Pelphrey, Singerman, et al., 2003; Pelphrey et al., 2004) modulates STS activity. Here, using event-related functional magnetic resonance imaging at 4 T, we investigated brain activity in response to passive viewing of goal- and non-goal- directed reaching-to-grasp movements. Participants viewed an animated character making reaching-to-grasp movements either toward (correct) or away (incorrect) from a blinking dial. Both conditions evoked significant posterior STS activity that was strongly right lateralized. By examining the time course of the blood oxygenation level-dependent response from areas of activation, we observed a functional dissociation. Incorrect trials evoked significantly greater activity in the STS than did correct trials, while an area posterior and inferior to the STS (likely corresponding to the MT/V5 complex) responded equally to correct and incorrect movements. Parietal cortical regions, including the superior parietal lobule and the anterior intraparietal sulcus, also responded equally to correct and incorrect movements, but showed evidence for differential responding based on the hand and arm (left or right) of the animated character used to make the reaching-to-grasp movement. The results of this study further suggest that a region of the right posterior STS is involved in analyzing the intentions of other peoples actions and that activity in this region is sensitive to the context of observed biological motions.

Perception of dynamic changes in facial affect and identity in autism

Despite elegant behavioral descriptions of abnormalities for processing emotional facial expressions and biological motion in autism, identification of the neural mechanisms underlying these abnormalities remains a critical and largely unmet challenge. We compared brain activity with dynamic and static facial expressions in participants with and without high-functioning autism using event-related functional magnetic resonance imaging (fMRI) and three classes of face stimuli-emotion morphs (fearful and angry), identity morphs and static images (fearful, angry and neutral). We observed reduced activity in the amygdala (AMY) and fusiform gyrus (FFG) to dynamic emotional expressions in people with autism. There was also a lack of modulation by dynamic compared with static emotional expressions of social brain regions including the AMY, posterior superior temporal sulcus (STS) region and FFG. We observed equivalent emotion and identity morph-evoked activity in participants with and without autism in a region corresponding to the expected location of the more generally motion-sensitive area MT or V5. We conclude that dysfunctions in key components of the human face processing system including the AMY, FFG and posterior STS region are present in individuals with high-functioning autism, and this dysfunction might contribute to the deficits in processing emotional facial expressions.

MicroRNAs Associated with Metastatic Prostate Cancer

Objective Metastasis is the most common cause of death of prostate cancer patients. Identification of specific metastasis biomarkers and novel therapeutic targets is considered essential for improved prognosis and management of the disease. MicroRNAs (miRNAs) form a class of non-coding small RNA molecules considered to be key regulators of gene expression. Their dysregulation has been shown to play a role in cancer onset, progression and metastasis, and miRNAs represent a promising new class of cancer biomarkers. The objective of this study was to identify down- and up-regulated miRNAs in prostate cancer that could provide potential biomarkers and/or therapeutic targets for prostate cancer metastasis. Methods Next generation sequencing technology was applied to identify differentially expressed miRNAs in a transplantable metastatic versus a non-metastatic prostate cancer xenograft line, both derived from one patients primary cancer. The xenografts were developed via subrenal capsule grafting of cancer tissue into NOD/SCID mice, a methodology that tends to preserve properties of the original cancers (e.g., tumor heterogeneity, genetic profiles). Results Differentially expressed known miRNAs, isomiRs and 36 novel miRNAs were identified. A number of these miRNAs (21/104) have previously been reported to show similar down- or up-regulation in prostate cancers relative to normal prostate tissue, and some of them (e.g., miR-16, miR-34a, miR-126*, miR-145, miR-205) have been linked to prostate cancer metastasis, supporting the validity of the analytical approach. Conclusions The use of metastatic and non-metastatic prostate cancer subrenal capsule xenografts derived from one patients cancer makes it likely that the differentially expressed miRNAs identified in this study include potential biomarkers and/or therapeutic targets for human prostate cancer metastasis.

DNA methylation of the oxytocin receptor gene predicts neural response to ambiguous social stimuli

Oxytocin and its receptor (OXTR) play an important role in a variety of social perceptual and affiliative processes. Individual variability in social information processing likely has a strong heritable component, and as such, many investigations have established an association between common genetic variants of OXTR and variability in the social phenotype. However, to date, these investigations have primarily focused only on changes in the sequence of DNA without considering the role of epigenetic factors. DNA methylation is an epigenetic mechanism by which cells control transcription through modification of chromatin structure. DNA methylation of OXTR decreases expression of the gene and high levels of methylation have been associated with autism spectrum disorders (ASD). This link between epigenetic variability and social phenotype allows for the possibility that social processes are under epigenetic control. We hypothesized that the level of DNA methylation of OXTR would predict individual variability in social perception. Using the brains sensitivity to displays of animacy as a neural endophenotype of social perception, we found significant associations between the degree of OXTR methylation and brain activity evoked by the perception of animacy. Our results suggest that consideration of DNA methylation may substantially improve our ability to explain individual differences in imaging genetic association studies.

Brain Mechanisms for Interpreting the Actions of Others From Biological-Motion Cues

Humans are an intensely social species. Our social abilities depend upon specialized brain systems for rapidly recognizing the faces of others, for interpreting the actions of others through an analysis of biological-motion cues, and for determining the emotional states of others via inspection of facial expression. Recent work has implicated the superior temporal sulcus (STS) region as an important component of the social brain. Functional neuroimaging studies have provided clues about how this region is involved in the visual analysis and interpretation of other peoples actions. STS activity is modulated by the context within which the actions of biological entities are observed. Such a contextual influence is consistent with a broader tradition within social psychology emphasizing the powerful influences of situational and contextual factors on behavior and perception. The STS region also shows promise as a region of importance in the investigation of both typical and impaired social-cognitive development. Future work should aim to inform us better of the development of interrelationships between the STS region and other regions of the social brain, including the amygdala and the fusiform gyrus.

Epigenetic modification of the oxytocin receptor gene influences the perception of anger and fear in the human brain

Significance Although understanding the precise nature of oxytocin’s influence on complex human social behavior has proven difficult, increasing evidence points to an anxiolytic effect. We use an imaging epigenetic approach to further parse oxytocin’s effects by examining a biological marker within the oxytocin system, DNA methylation of the oxytocin receptor gene (OXTR). Importantly, this epigenetic modification directly impacts the expression of oxytocin’s receptor, which is critical for the actions of oxytocin to have an effect. We find that higher levels of OXTR methylation are associated with increased neural response and decreased functional coupling within regions supporting social perception and emotion processing. This pattern of activity may be indicative of diminished emotion regulation to negative stimuli and increased risk of pathology. In humans, the neuropeptide oxytocin plays a critical role in social and emotional behavior. The actions of this molecule are dependent on a protein that acts as its receptor, which is encoded by the oxytocin receptor gene (OXTR). DNA methylation of OXTR, an epigenetic modification, directly influences gene transcription and is variable in humans. However, the impact of this variability on specific social behaviors is unknown. We hypothesized that variability in OXTR methylation impacts social perceptual processes often linked with oxytocin, such as perception of facial emotions. Using an imaging epigenetic approach, we established a relationship between OXTR methylation and neural activity in response to emotional face processing. Specifically, high levels of OXTR methylation were associated with greater amounts of activity in regions associated with face and emotion processing including amygdala, fusiform, and insula. Importantly, we found that these higher levels of OXTR methylation were also associated with decreased functional coupling of amygdala with regions involved in affect appraisal and emotion regulation. These data indicate that the human endogenous oxytocin system is involved in attenuation of the fear response, corroborating research implicating intranasal oxytocin in the same processes. Our findings highlight the importance of including epigenetic mechanisms in the description of the endogenous oxytocin system and further support a central role for oxytocin in social cognition. This approach linking epigenetic variability with neural endophenotypes may broadly explain individual differences in phenotype including susceptibility or resilience to disease.

Identification of high risk subsets of acute myocardial infarction

To Identify the patient at high risk after acute myocardial Infarction data on 400 patients obtained from the Myocardial Infarction Research Units Cooperative Data Bank were examined. Patients were grouped according to clinical findings as follows: uncomplicated (class 1, 81 patients); mild to moderate failure (class II, 150 patients); severe failure with pulmonary edema (class III, 17 patients); and severe failure with shock (class IV, 152 patients). Hemodynamic data Including pulmonary capillary wedge pressure and cardiac output were available In all patients. High risk subsets within clinical classes I, II and IV were Identifiable. In class I, nonsurvivors had significantly (P <0.05) higher values for pulmonary capillary wedge pressure (16 mm Hg) and heart rate (96 beats/min); nonsurvivors In class II also had a significant (P <0.01) elevation In pulmonary capillary wedge pressure (23 mm Hg); and In class IV the high risk subset was characterized (P <0.01) by pulmonary capillary wedge pressure (21 mm Hg), heart rate (100 beats/min), cardiac Index (1.6 liters/min per m2), stroke index (14 cc/m2) and stroke work index (12 g-m/m2). Discrimlnant function analysis using pulmonary capillary wedge pressure and heart rate predicted mortality In classes I to III with 72 percent accuracy; a similar equation representing stroke work index, pulmonary capillary wedge pressure and cardiac Index had an 83 percent rate of accuracy in class IV patients. interclass comparison of the last three measurements indicated that the data differed significantly among classes, thus signifying a spectrum of ventricular impairment after Infarction that was commensurate with the clinical presentation. However, in individual patients the clinical examination did not consistently reflect the degree of ventricular dysfunction. Thus, careful bedside examination together with hemodynamic monitoring of wedge pressure, cardiac output and heart rate serve to identify the high risk patient after acute myocardial infarction.

Regional Brain Activation Evoked When Approaching a Virtual Human on a Virtual Walk

We investigated the necessity of biological motion for activation of the posterior superior temporal sulcus (pSTS) in circumstances in which the rapid approach of the observer to a virtual human induced the observer to make inferences about the characters intentions. Using a virtual reality environment, subjects experienced themselves walking towards a complex scene composed of animate and/or inanimate objects. During person trials, the scene contained a virtual human either making a simple gesture such as scratching his face (Study 1) or standing completely still (Study 2). During object trials, the scenes contained items such as furniture, a face portrait, and a clock, but not the virtual human. Using functional MRI to measure brain activity, we demonstrated strong activity in the pSTS while the observer approached the social scene, but only when the virtual human was making gestures. This result emphasizes the importance of biological motion in inferring the intentions of others.

Review of the treatment literature for encopresis, functional constipation, and stool-toileting refusal

This review summarizes the literature on randomized, controlled, published studies involving medical, behavioral, psychological, and biofeedback treatments for encopresis/functional constipation and stool-toileting refusal in preschool-age and school-age children. Nine such studies were located in the literature involving school-age children. No randomized, controlled treatment studies involving preschool-age children have been published. This review revealed no evidence to support the routine use of psychotherapy or anal sphincter biofeedback in the treatment of pediatric fecal elimination dysfunctions, beyond those benefits derived from a comprehensive medical-behavioral intervention. Further, this review indicated that paradoxical constriction of the External Anal Sphincter does not influence the treatment outcome of either biofeedback or medical-behavioral interventions. There are remarkably few controlled treatment outcome studies in this most important clinical area. More research is needed that employs standard treatment outcome variables.

Individual differences in personality predict how people look at faces.

Background Determining the ways in which personality traits interact with contextual determinants to shape social behavior remains an important area of empirical investigation. The specific personality trait of neuroticism has been related to characteristic negative emotionality and associated with heightened attention to negative, emotionally arousing environmental signals. However, the mechanisms by which this personality trait may shape social behavior remain largely unspecified. Methodology/Principal Findings We employed eye tracking to investigate the relationship between characteristics of visual scanpaths in response to emotional facial expressions and individual differences in personality. We discovered that the amount of time spent looking at the eyes of fearful faces was positively related to neuroticism. Conclusions/Significance This finding is discussed in relation to previous behavioral research relating personality to selective attention for trait-congruent emotional information, neuroimaging studies relating differences in personality to amygdala reactivity to socially relevant stimuli, and genetic studies suggesting linkages between the serotonin transporter gene and neuroticism. We conclude that personality may be related to interpersonal interaction by shaping aspects of social cognition as basic as eye contact. In this way, eye gaze represents a possible behavioral link in a complex relationship between genes, brain function, and personality.