Memory bias for emotional facial expressions in major depression

Sixteen clinically depressed patients and sixteen healthy controls were presented with a set of emotional facial expressions and were asked to identify the emotion portrayed by each face. They, were subsequently given a recognition memory test for these faces. There was no difference between the groups in terms of their ability to identify emotion between from faces. All participants identified emotional expressions more accurately than neutral expressions, with happy expressions being identified most accurately. During the recognition memory phase the depressed patients demonstrated superior memory for sad expressions, and inferior memory for happy expressions, relative to neutral expressions. Conversely, the controls demonstrated superior memory for happy expressions, and inferior memory for sad expressions, relative to neutral expressions. These results are discussed in terms of the cognitive model of depression proposed by Williams, Watts, MacLeod, and Mathews (1997).

Genetic modulation of the response bias towards facial displays of anger and happiness

Background: Investigating genetic modulation of emotion processing may contribute to the understanding of heritable mechanisms of emotional disorders. The aim of the present study was to test the effects of catechol- O-methyltransferase (COMT) val158met and serotonin-transporter-linked promoter region (5-HTTLPR) polymorphisms on facial emotion processing in healthy individuals. Methods: Two hundred and seventy five (167 female) participants were asked to complete a computerized facial affect recognition task, which involved four experimental conditions, each containing one type of emotional face (fearful, angry, sad or happy) intermixed with neutral faces. Participants were asked to indicate whether the face displayed an emotion or was neutral. The COMT-val158met and 5-HTTLPR polymorphisms were genotyped. Results: Met homozygotes (COMT) showed a stronger bias to perceive neutral faces as expressions of anger, compared with val homozygotes. However, the S-homozygotes (5-HTTLPR) showed a reduced bias to perceive neutral faces as expressions of happiness, compared to L-homozygotes. No interaction between 5-HTTLPR and COMT was found. Conclusions: These results add to the knowledge of individual differences in social cognition that are modulated via serotonergic and dopaminergic systems. This potentially could contribute to the understanding of the mechanisms of susceptibility to emotional disorders. © 2013 Elsevier Masson SAS.

Independent modulation of engagement and connectivity of the facial network during affect processing by CACNA1C and ANK3 risk genes for bipolar disorder

IMPORTANCE Genome-wide association studies (GWASs) indicate that single-nucleotide polymorphisms in the CACNA1C and ANK3 genes increase the risk for bipolar disorder (BD). The genes influence neuronal firing by modulating calcium and sodium channel functions, respectively. Both genes modulate ?-aminobutyric acid-transmitting interneuron function and can thus affect brain regional activation and interregional connectivity. OBJECTIVE To determine whether the genetic risk for BD associated with 2 GWAS-supported risk single-nucleotide polymorphisms at CACNA1C rs1006737 and ANK3 rs10994336 is mediated through changes in regional activation and interregional connectivity of the facial affect-processing network. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional functional magnetic resonance imaging study at a research institute of 41 euthymic patients with BD and 46 healthy participants, all of British white descent. MAIN OUTCOMES AND MEASURES Blood oxygen level-dependent signal and effective connectivity measures during the facial affect-processing task. RESULTS In healthy carriers, both genetic risk variants were independently associated with increased regional engagement throughout the facial affect-processing network and increased effective connectivity between the visual and ventral prefrontal cortical regions. In contrast, BD carriers of either genetic risk variant exhibited pronounced reduction in ventral prefrontal cortical activation and visual-prefrontal effective connectivity. CONCLUSIONS AND RELEVANCE Our data demonstrate that the effect of CACNA1C rs1006737 and ANK3 rs10994336 (or genetic variants in linkage disequilibrium) on the brain converges on the neural circuitry involved in affect processing and provides a mechanism linking BD to genome-wide genetic risk variants.

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

Background - The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. Method - We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. Results - Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. Conclusions - Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity. © 2010 Cambridge University Press.

The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition:a fMRI study

The functional catechol-O-methyltransferase (COMT Val108/158Met) polymorphism has been shown to have an impact on tasks of executive function, memory and attention and recently, tasks with an affective component. As oestrogen reduces COMT activity, we focused on the interaction between gender and COMT genotype on brain activations during an affective processing task. We used functional MRI (fMRI) to record brain activations from 74 healthy subjects who engaged in a facial affect recognition task; subjects viewed and identified fearful compared to neutral faces. There was no main effect of the COMT polymorphism, gender or genotypegender interaction on task performance. We found a significant effect of gender on brain activations in the left amygdala and right temporal pole, where females demonstrated increased activations over males. Within these regions, Val/Val carriers showed greater signal magnitude compared to Met/Met carriers, particularly in females. The COMT Val108/158Met polymorphism impacts on gender-related patterns of activation in limbic and paralimbic regions but the functional significance of any oestrogen-related COMT inhibition appears modest. Copyright © 2008 CINP.

Pilot investigation of the changes in cortical activation during facial affect recognition with lamotrigine monotherapy in bipolar disorder

Background: Bipolar disorder is associated with dysfunction in prefrontal and limbic areas implicated in emotional processing. Aims: To explore whether lamotrigine monotherapy may exert its action by improving the function of the neural network involved in emotional processing. Method: We used functional magnetic resonance imaging to examine changes in brain activation during a sad facial affect recognition task in 12 stable patients with bipolar disorder when medication-free compared with healthy controls and after 12 weeks of lamotrigine monotherapy. Results: At baseline, compared with controls, patients with bipolar disorder showed overactivity in temporal regions and underactivity in the dorsal medial and right ventrolateral prefrontal cortex, and the dorsal cingulate gyrus. Following lamotrigine monotherapy, patients demonstrated reduced temporal and increased prefrontal activation. Conclusions: This preliminary evidence suggests that lamotrigine may enhance the function of the neural circuitry involved in affect recognition.

The integration of ProxiMAX randomisation with CIS display for the high-throughput production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering. This can allow the analysis of potential new properties thus allowing key residues within a protein to be targeted and randomised. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK) has inherent redundancy and disparities in residue representation. In this we describe the combination of ProxiMAX randomisation and CIS display for the use of generating novel peptides. Unlike other methods ProxiMAX randomisation does not require any intricate chemistry but simply utilises synthetic DNA and molecular biology techniques. Designed ‘MAX’ oligonucleotides were ligated, amplified and digested in an iterative cycle. Results show that randomised ‘MAX’ codons can be added sequentially to the base sequence creating a series of randomised non-degenerate codons that can subsequently be inserted into a gene. CIS display (Isogencia, UK) is an in vitro DNA based screening method that creates a genotype to phenotype link between a peptide and the nucleic acid that encodes it. The use of straight forward in vitro transcription/translation and other molecular biology techniques permits ease of use along with flexibility making it a potent screening technique. Using ProxiMAX randomisation in combination with CIS display, the aim is to produce randomised anti-nerve growth factor (NGF) and calcitonin gene-related (CGRP) peptides to demonstrate the high-throughput nature of this combination.

Channeled spectrum display using a CCD array for student laboratory demonstrations

The channelled spectrum of an optical beam generated by a laser diode operated below threshold after traversing microscope glass plates is spectrally analysed using a grating and a CCD linear array. The experiment has the following goals: to display the resulting channelled spectrum, to familiarize students with an important topic in metrology and to illustrate some interesting topics from spectroscopy using a CCD array as a spectrometer.

The development of a symptom questionnaire for assessing virtual reality viewing using a head-mounted display

ABSTRACT: Purpose. Virtual reality devices, including virtual reality head-mounted displays, are becoming increasingly accessible to the general public as technological advances lead to reduced costs. However, there are numerous reports that adverse effects such as ocular discomfort and headache are associated with these devices. To investigate these adverse effects, questionnaires that have been specifically designed for other purposes such as investigating motion sickness have often been used. The primary purpose of this study was to develop a standard questionnaire for use in investigating symptoms that result from virtual reality viewing. In addition, symptom duration and whether priming subjects elevates symptom ratings were also investigated. Methods. A list of the most frequently reported symptoms following virtual reality viewing was determined from previously published studies and used as the basis for a pilot questionnaire. The pilot questionnaire, which consisted of 12 nonocular and 11 ocular symptoms, was administered to two groups of eight subjects. One group was primed by having them complete the questionnaire before immersion; the other group completed the questionnaire postviewing only. Postviewing testing was carried out immediately after viewing and then at 2-min intervals for a further 10 min. Results. Priming subjects did not elevate symptom ratings; therefore, the data were pooled and 16 symptoms were found to increase significantly. The majority of symptoms dissipated rapidly, within 6 min after viewing. Frequency of endorsement data showed that approximately half of the symptoms on the pilot questionnaire could be discarded because <20% of subjects experienced them. Conclusions. Symptom questionnaires to investigate virtual reality viewing can be administered before viewing, without biasing the findings, allowing calculation of the amount of change from pre- to postviewing. However, symptoms dissipate rapidly and assessment of symptoms needs to occur in the first 5 min postviewing. Thirteen symptom questions, eight nonocular and five ocular, were determined to be useful for a questionnaire specifically related to virtual reality viewing using a head-mounted display.

Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression

Impaired facial expression recognition has been associated with features of major depression, which could underlie some of the difficulties in social interactions in these patients. Patients with major depressive disorder and age- and gender-matched healthy volunteers judged the emotion of 100 facial stimuli displaying different intensities of sadness and happiness and neutral expressions presented for short (100 ms) and long (2,000 ms) durations. Compared with healthy volunteers, depressed patients demonstrated subtle impairments in discrimination accuracy and a predominant bias away from the identification as happy of mildly happy expressions. The authors suggest that, in depressed patients, the inability to accurately identify subtle changes in facial expression displayed by others in social situations may underlie the impaired interpersonal functioning.

Producing facial composite sketches in remote cognitive interviews:a preliminary investigation

Justice systems around the world are increasingly turning to videoconferencing as a means to reduce delays and reduce costs in legal processes. This preliminary research examined whether interviewing a witness remotely - without physical co-presence of the witness and interviewer - could facilitate the production of quality facial composite sketches of suspects. In Study 1, 42 adults briefly viewed a photograph of a face. The next day they participated in Cognitive Interviews with a forensic artist, conducted either face-to-face or remotely via videoconference. In Study 2, 20 adults participated in videoconferenced interviews, and we manipulated the method by which they viewed the developing sketch. In both studies, independent groups of volunteers rated the likeness of the composites to the original photographs. The data suggest that remote interviews elicited effective composites; however, in Study 1 these composites were considered poorer matches to the photographs than were those produced in face-to-face interviews. The differences were small, but significant. Participants perceived several disadvantages to remote interviewing, but also several advantages including less pressure and better concentration. The results of Study 2 suggested that different sketch presentation methods offered different benefits. We propose that remote interviewing could be a useful tool for investigators in certain circumstances. © 2013 Taylor & Francis.

Look who's talking! Facial appearance can bias source monitoring

When we see a stranger's face we quickly form impressions of his or her personality, and expectations of how the stranger might behave. Might these intuitive character judgements bias source monitoring? Participants read headlines "reported" by a trustworthy- and an untrustworthy-looking reporter. Subsequently, participants recalled which reporter provided each headline. Source memory for likely-sounding headlines was most accurate when a trustworthy-looking reporter had provided the headlines. Conversely, source memory for unlikely-sounding headlines was most accurate when an untrustworthy-looking reporter had provided the headlines. This bias appeared to be driven by the use of decision criteria during retrieval rather than differences in memory encoding. Nevertheless, the bias was apparently unrelated to variations in subjective confidence. These results show for the first time that intuitive, stereotyped judgements of others' appearance can bias memory attributions analogously to the biases that occur when people receive explicit information to distinguish sources. We suggest possible real-life consequences of these stereotype-driven source-monitoring biases. © 2010 Psychology Press.

Implementing an agent-based model with a spatial visual display in discrete-event simulation software

There has been an increasing interest in the use of agent-based simulation and some discussion of the relative merits of this approach as compared to discrete-event simulation. There are differing views on whether an agent-based simulation offers capabilities that discrete-event cannot provide or whether all agent-based applications can at least in theory be undertaken using a discrete-event approach. This paper presents a simple agent-based NetLogo model and corresponding discrete-event versions implemented in the widely used ARENA software. The two versions of the discrete-event model presented use a traditional process flow approach normally adopted in discrete-event simulation software and also an agent-based approach to the model build. In addition a real-time spatial visual display facility is provided using a spreadsheet platform controlled by VBA code embedded within the ARENA model. Initial findings from this investigation are that discrete-event simulation can indeed be used to implement agent-based models and with suitable integration elements such as VBA provide the spatial displays associated with agent-based software.

Dissociation of detection and evaluation of facial expressions in adolescence

Holistic face perception, i.e. the mandatory integration of featural information across the face, hasbeen considered to play a key role when recognizing emotional face expressions (e.g., Tanaka et al.,2002). However, despite their early onset holistic processing skills continue to improvethroughout adolescence (e.g., Schwarzer et al., 2010) and therefore might modulate theevaluation of facial expressions. We tested this hypothesis using an attentional blink (AB)paradigm to compare the impact of happy, fearful and neutral faces in adolescents (10–13 years)and adults on subsequently presented neutral target stimuli (animals, plants and objects) in a rapidserial visual presentation stream. Adolescents and adults were found to be equally reliable whenreporting the emotional expression of the face stimuli. However, the detection of emotional butnot neutral faces imposed a significantly stronger AB effect on the detection of the neutral targetsin adults compared to adolescents. In a control experiment we confirmed that adolescents ratedemotional faces lower in terms of valence and arousal than adults. The results suggest a protracteddevelopment of the ability to evaluate facial expressions that might be attributed to the latematuration of holistic processing skills.

The integration of ProxiMAX randomisation with CIS display for the production of novel peptides

Saturation mutagenesis is a powerful tool in modern protein engineering, which permits key residues within a protein to be targeted in order to potentially enhance specific functionalities. However, the creation of large libraries using conventional saturation mutagenesis with degenerate codons (NNN or NNK/S) has inherent redundancy and consequent disparities in codon representation. Therefore, both chemical (trinucleotide phosphoramidites) and biological methods (sequential, enzymatic single codon additions) of non-degenerate saturation mutagenesis have been developed in order to combat these issues and so improve library quality. Large libraries with multiple saturated positions can be limited by the method used to screen them. Although the traditional screening method of choice, cell-dependent methods, such as phage display, are limited by the need for transformation. A number of cell-free screening methods, such as CIS display, which link the screened phenotype with the encoded genotype, have the capability of screening libraries with up to 1014 members. This thesis describes the further development of ProxiMAX technology to reduce library codon bias and its integration with CIS display to screen the resulting library. Synthetic MAX oligonucleotides are ligated to an acceptor base sequence, amplified, and digested, subsequently adding a randomised codon to the acceptor, which forms an iterative cycle using the digested product of the previous cycle as the base sequence for the next. Initial use of ProxiMAX highlighted areas of the process where changes could be implemented in order to improve the codon representation in the final library. The refined process was used to construct a monomeric anti-NGF peptide library, based on two proprietary dimeric peptides (Isogenica) that bind NGF. The resulting library showed greatly improved codon representation that equated to a theoretical diversity of ~69%. The library was subsequently screened using CIS display and the discovered peptides assessed for NGF-TrkA inhibition by ELISA. Despite binding to TrkA, these peptides showed lower levels of inhibition of the NGF-TrkA interaction than the parental dimeric peptides, highlighting the importance of dimerization for inhibition of NGF-TrkA binding.