Facial expression processing in developmental prosopagnosia

<p>Individuals with developmental prosopagnosia experience lifelong deficits recognising facial identity, but whether their ability to process facial expression is also impaired is unclear. Addressing this issue is key for understanding the core deficit in developmental prosopagnosia, and for advancing knowledge about the mechanisms and development of normal face processing. In this thesis, I report two online studies on facial expression processing with large samples of prosopagnosics. In Study 1, I compared facial expression and facial identity perception in 124 prosopagnosics and 133 controls. I used three perceptual tasks including simultaneous matching, sequential matching, and sorting. I also measured inversion effects to examine whether prosopagnosics rely on typical face mechanisms. Prosopagnosics showed subtle deficits with facial expression, but they performed worse with facial identity. Prosopagnosics also showed reduced inversion effects for facial identity but normal inversion effects for facial expression, suggesting they use atypical mechanisms for facial identity but normal mechanisms for facial expression. In Study 2, I extended the findings of Study 1 by assessing facial expression recognition in 78 prosopagnosics and 138 controls. I used four labelling tasks that varied on whether the facial expressions were basic (e.g., happy) or complex (e.g., elated), and whether they were displayed via static (i.e., images) or dynamic (i.e., video clips) stimuli. Prosopagnosics showed subtle deficits with basic expressions but performed normally with complex expressions. Further, prosopagnosics did not show reduced inversion effects for both types of expressions, suggesting they use similar recognition mechanisms as controls. Critically, the subtle expression deficits that prosopagnosics showed in both studies can be accounted for by autism traits, suggesting that expression deficits are not a feature of prosopagnosia per se. I also provide estimates of the prevalence of deficits in facial expression perception (7.70%) and recognition (2.56% - 5.13%) in prosopagnosia, both of which suggest that facial expression processing is normal in the majority of prosopagnosics. Overall, my thesis demonstrates that facial expression processing is not impaired in developmental prosopagnosia, and suggests that facial expression and facial identity processing rely on separate mechanisms that dissociate in development.</p>

Facial expression processing in developmental prosopagnosia

<p>Individuals with developmental prosopagnosia experience lifelong deficits recognising facial identity, but whether their ability to process facial expression is also impaired is unclear. Addressing this issue is key for understanding the core deficit in developmental prosopagnosia, and for advancing knowledge about the mechanisms and development of normal face processing. In this thesis, I report two online studies on facial expression processing with large samples of prosopagnosics. In Study 1, I compared facial expression and facial identity perception in 124 prosopagnosics and 133 controls. I used three perceptual tasks including simultaneous matching, sequential matching, and sorting. I also measured inversion effects to examine whether prosopagnosics rely on typical face mechanisms. Prosopagnosics showed subtle deficits with facial expression, but they performed worse with facial identity. Prosopagnosics also showed reduced inversion effects for facial identity but normal inversion effects for facial expression, suggesting they use atypical mechanisms for facial identity but normal mechanisms for facial expression. In Study 2, I extended the findings of Study 1 by assessing facial expression recognition in 78 prosopagnosics and 138 controls. I used four labelling tasks that varied on whether the facial expressions were basic (e.g., happy) or complex (e.g., elated), and whether they were displayed via static (i.e., images) or dynamic (i.e., video clips) stimuli. Prosopagnosics showed subtle deficits with basic expressions but performed normally with complex expressions. Further, prosopagnosics did not show reduced inversion effects for both types of expressions, suggesting they use similar recognition mechanisms as controls. Critically, the subtle expression deficits that prosopagnosics showed in both studies can be accounted for by autism traits, suggesting that expression deficits are not a feature of prosopagnosia per se. I also provide estimates of the prevalence of deficits in facial expression perception (7.70%) and recognition (2.56% - 5.13%) in prosopagnosia, both of which suggest that facial expression processing is normal in the majority of prosopagnosics. Overall, my thesis demonstrates that facial expression processing is not impaired in developmental prosopagnosia, and suggests that facial expression and facial identity processing rely on separate mechanisms that dissociate in development.</p>

Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges

Across a broad range of human cancers, gain-of-function mutations in RAS genes (HRAS, NRAS, and KRAS) lead to constitutive activity of oncoproteins responsible for tumorigenesis and cancer progression. The targeting of RAS with drugs is challenging because RAS lacks classic and tractable drug binding sites. Over the past 30 years, this perception has led to the pursuit of indirect routes for targeting RAS expression, processing, upstream regulators, or downstream effectors. After the discovery that the KRAS-G12C variant contains a druggable pocket below the switch-II loop region, it has become possible to design irreversible covalent inhibitors for the variant with improved potency, selectivity and bioavailability. Two such inhibitors, sotorasib (AMG 510) and adagrasib (MRTX849), were recently evaluated in phase I-III trials for the treatment of non-small cell lung cancer with KRAS-G12C mutations, heralding a new era of precision oncology. In this review, we outline the mutations and functions of KRAS in human tumors and then analyze indirect and direct approaches to shut down the oncogenic KRAS network. Specifically, we discuss the mechanistic principles, clinical features, and strategies for overcoming primary or secondary resistance to KRAS-G12C blockade.

Left Hemisphere Dominance for Negative Facial Expressions: The Influence of Task

Major theories of hemisphere asymmetries in facial expression processing predict right hemisphere dominance for negative facial expressions of disgust, fear, and sadness, however, some studies observe left hemisphere dominance for one or more of these expressions. Research suggests that tasks requiring the identification of six basic emotional facial expressions (angry, disgusted, fearful, happy, sad, and surprised) are more likely to produce left hemisphere involvement than tasks that do not require expression identification. The present research investigated this possibility in two experiments that presented six basic emotional facial expressions to the right or left hemisphere using a divided-visual field paradigm. In Experiment 1, participants identified emotional expressions by pushing a key corresponding to one of six labels. In Experiment 2, participants detected emotional expressions by pushing a key corresponding to whether an expression was emotional or not. In line with predictions, fearful facial expressions exhibited a left hemisphere advantage during the identification task but not during the detection task. In contrast to predictions, sad expressions exhibited a left hemisphere advantage during both identification and detection tasks. In addition, happy facial expressions exhibited a left hemisphere advantage during the detection task but not during the identification task. Only angry facial expressions exhibited a right hemisphere advantage, and this was only observed when data from both experiments were combined. Together, results highlight the influence of task demands on hemisphere asymmetries in facial expression processing and suggest a greater role for the left hemisphere in negative expressions than predicted by previous theories.

Altered effective connectivity of the extended face processing system in depression and its association with treatment response: findings from the YoDA-C randomized controled trial

Background Depression is commonly associated with fronto-amygdala dysfunction during the processing of emotional face expressions. Interactions between these regions are hypothesized to contribute to negative emotional processing biases and as such have been highlighted as potential biomarkers of treatment response. This study aimed to investigate depression associated alterations to directional connectivity and assess the utility of these parameters as predictors of treatment response. Methods Ninety-two unmedicated adolescents and young adults (mean age 20.1; 56.5% female) with moderate-to-severe major depressive disorder and 88 healthy controls (mean age 19.8; 61.4% female) completed an implicit emotional face processing fMRI task. Patients were randomized to receive cognitive behavioral therapy for 12 weeks, plus either fluoxetine or placebo. Using dynamic causal modelling, we examined functional relationships between six brain regions implicated in emotional face processing, comparing both patients and controls and treatment responders and non-responders. Results Depressed patients demonstrated reduced inhibition from the dlPFC to vmPFC and reduced excitation from the dlPFC to amygdala during sad expression processing. During fearful expression processing patients showed reduced inhibition from the vmPFC to amygdala and reduced excitation from the amygdala to dlPFC. Response was associated with connectivity from the amygdala to dlPFC during sad expression processing and amygdala to vmPFC connectivity during fearful expression processing. Conclusions Our study clarifies the nature of face processing network alterations in adolescents and young adults with depression, highlighting key interactions between the amygdala and prefrontal cortex. Moreover, these findings highlight the potential utility of these interactions in predicting treatment response.

A shared mechanism for facial expression in human faces and face pareidolia

Facial expressions are vital for social communication, yet the underlying mechanisms are still being discovered. Illusory faces perceived in objects (face pareidolia) are errors of face detection that share some neural mechanisms with human face processing. However, it is unknown whether expression in illusory faces engages the same mechanisms as human faces. Here, using a serial dependence paradigm, we investigated whether illusory and human faces share a common expression mechanism. First, we found that images of face pareidolia are reliably rated for expression, within and between observers, despite varying greatly in visual features. Second, they exhibit positive serial dependence for perceived facial expression, meaning an illusory face (happy or angry) is perceived as more similar in expression to the preceding one, just as seen for human faces. This suggests illusory and human faces engage similar mechanisms of temporal continuity. Third, we found robust cross-domain serial dependence of perceived expression between illusory and human faces when they were interleaved, with serial effects larger when illusory faces preceded human faces than the reverse. Together, the results support a shared mechanism for facial expression between human faces and illusory faces and suggest that expression processing is not tightly bound to human facial features.

The cerebellum as a moderator of negative bias of facial expression processing in depressive patients

Background: Negative bias-a mood-congruent bias in emotion processing-is an important aspect of major depressive disorder (MDD), and such a bias in facial expression recognition has a significant effect on patients' social lives. Neuroscience research shows abnormal activity in emotion-processing systems regarding facial expressions in MDD. However, the neural basis of negative bias in facial expression processing has not been explored directly. Methods: Sixteen patients with MDD and twenty-three healthy controls (HC) who underwent an fMRI scan during an explicit facial emotion task with happy to sad faces were selected. We identified brain areas in which the MDD and HC groups showed different correlations between the behavioral negative bias scores and functional activities. Results: Behavioral data confirmed the existence of a higher negative bias in the MDD group. Regarding the relationship with neural activity, higher activity of happy faces in the posterior cerebellum was related to a higher negative bias in the MDD group, but lower negative bias in the HC group. Limitations: The sample size was small, and the possible effects of medication were not controlled for in this study. Conclusions: We confirmed a negative bias in the recognition of facial expressions in patients with MDD. fMRI data suggest the cerebellum as a moderator of facial emotion processing, which biases the recognition of facial expressions toward their own mood.

Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

A number of studies performed on rodents suggest that insulin-like growth factor 2 (IGF-2) or its analogs may possibly be used for treating some conditions like Alzheimer’s disease, Huntington’s disease, autistic spectrum disorders or aging-related cognitive impairment. Still, for translational research a comparative knowledge about the function of IGF-2 and related molecules in model organisms (rats and mice) and humans is necessary. There is a number of important differences in IGF-2 signaling between species. In the present review we emphasize species-specific patterns of IGF-2 expression in rodents, humans and some other mammals, using, among other sources, publicly available transcriptomic data. We provide a detailed description of Igf2 mRNA expression regulation and pre-pro-IGF-2 protein processing in different species. We also summarize the function of IGF-binding proteins. We describe three different receptors able to bind IGF-2 and discuss the role of IGF-2 signaling in learning and memory, as well as in neuroprotection. We hope that comprehensive understanding of similarities and differences in IGF-2 signaling between model organisms and humans will be useful for development of more effective medicines targeting IGF-2 receptors.