Facial affect processing inbipolar disorder:a magnetoencephalography study

Background: Identifying biological markers to aid diagnosis of bipolar disorder (BD) is critically important. To be considered a possible biological marker, neural patterns in BD should be discriminant from those in healthy individuals (HI). We examined patterns of neuromagnetic responses revealed by magnetoencephalography (MEG) during implicit emotion-processing using emotional (happy, fearful, sad) and neutral facial expressions, in sixteen BD and sixteen age- and gender-matched healthy individuals. Methods: Neuromagnetic data were recorded using a 306-channel whole-head MEG ELEKTA Neuromag System, and preprocessed using Signal Space Separation as implemented in MaxFilter (ELEKTA). Custom Matlab programs removed EOG and ECG signals from filtered MEG data, and computed means of epoched data (0-250ms, 250-500ms, 500-750ms). A generalized linear model with three factors (individual, emotion intensity and time) compared BD and HI. A principal component analysis of normalized mean channel data in selected brain regions identified principal components that explained 95% of data variation. These components were used in a quadratic support vector machine (SVM) pattern classifier. SVM classifier performance was assessed using the leave-one-out approach. Results: BD and HI showed significantly different patterns of activation for 0-250ms within both left occipital and temporal regions, specifically for neutral facial expressions. PCA analysis revealed significant differences between BD and HI for mild fearful, happy, and sad facial expressions within 250-500ms. SVM quadratic classifier showed greatest accuracy (84%) and sensitivity (92%) for neutral faces, in left occipital regions within 500-750ms. Conclusions: MEG responses may be used in the search for disease specific neural markers.

Facial emotion recognition and alexithymia in adults with somatoform disorders

The primary aim of this study was to investigate facial emotion recognition (FER) in patients with somatoform disorders (SFD). Also of interest was the extent to which concurrent alexithymia contributed to any changes in emotion recognition accuracy. Twenty patients with SFD and 20 healthy, age, sex and education matched, controls were assessed with the Facially Expressed Emotion Labelling Test of FER and the 26-item Toronto Alexithymia Scale. Patients withSFD exhibited elevated alexithymia symptoms relative to healthy controls.Patients with SFD also recognized significantly fewer emotional expressions than did the healthy controls. However, the group difference in emotion recognition accuracy became nonsignificant once the influence of alexithymia was controlled for statistically. This suggests that the deficit in FER observed in the patients with SFD was most likely a consequence of concurrent alexithymia. It should be noted that neither depression nor anxiety was significantly related to emotion recognition accuracy, suggesting that these variables did not contribute the emotion recognition deficit. Impaired FER observed in the patients with SFD could plausibly have a negative influence on these individuals’ social functioning.

Differential patterns of activity and functional connectivity in emotion processing neural circuitry to angry and happy faces in adolescents with and without suicide attempt

Background - Neural substrates of emotion dysregulation in adolescent suicide attempters remain unexamined. Method - We used functional magnetic resonance imaging to measure neural activity to neutral, mild or intense (i.e. 0%, 50% or 100% intensity) emotion face morphs in two separate emotion-processing runs (angry and happy) in three adolescent groups: (1) history of suicide attempt and depression (ATT, n = 14); (2) history of depression alone (NAT, n = 15); and (3) healthy controls (HC, n = 15). Post-hoc analyses were conducted on interactions from 3 group × 3 condition (intensities) whole-brain analyses (p < 0.05, corrected) for each emotion run. Results - To 50% intensity angry faces, ATT showed significantly greater activity than NAT in anterior cingulate gyral–dorsolateral prefrontal cortical attentional control circuitry, primary sensory and temporal cortices; and significantly greater activity than HC in the primary sensory cortex, while NAT had significantly lower activity than HC in the anterior cingulate gyrus and ventromedial prefrontal cortex. To neutral faces during the angry emotion-processing run, ATT had significantly lower activity than NAT in the fusiform gyrus. ATT also showed significantly lower activity than HC to 100% intensity happy faces in the primary sensory cortex, and to neutral faces in the happy run in the anterior cingulate and left medial frontal gyri (all p < 0.006,corrected). Psychophysiological interaction analyses revealed significantly reduced anterior cingulate gyral–insula functional connectivity to 50% intensity angry faces in ATT v. NAT or HC. Conclusions - Elevated activity in attention control circuitry, and reduced anterior cingulate gyral–insula functional connectivity, to 50% intensity angry faces in ATT than other groups suggest that ATT may show inefficient recruitment of attentional control neural circuitry when regulating attention to mild intensity angry faces, which may represent a potential biological marker for suicide risk.

The influence of emotional intensity on facial emotion recognition in disordered eating

Significant facial emotion recognition (FER) deficits have been observed in participants exhibiting high levels of eating psychopathology. The current study aimed to determine if the pattern of FER deficits is influenced by intensity of facial emotion and to establish if eating psychopathology is associated with a specific pattern of emotion recognition errors that is independent of other psychopathological or personality factors. Eighty females, 40 high and 40 low scorers on the Eating Disorders Inventory (EDI) were presented with a series of faces, each featuring one of five emotional expressions at one of four intensities, and were asked to identify the emotion portrayed. Results revealed that, in comparison to Low EDI scorers, high scorers correctly recognised significantly fewer expressions, particularly of fear and anger. There was also a trend for this deficit to be more evident for subtle displays of emotion (50% intensity). Deficits in anger recognition were related specifically to scores on the body dissatisfaction subscale of the EDI. Error analyses revealed that, in comparison to Low EDI scorers, high scorers made significantly more and fear-as-anger errors. Also, a tendency to label anger expressions as sadness was related to body dissatisfaction. Current findings confirm FER deficits in subclinical eating psychopathology and extend these findings to subtle expressions of emotion. Furthermore, this is the first study to establish that these deficits are related to a specific pattern of recognition errors. Impaired FER could disrupt normal social functioning and might represent a risk factor for the development of more severe psychopathology.

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.

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.

Investigation of neural correlates of faces and emotional expressions using magnetoencephalography

The recognition of faces and of facial expressions in an important evolutionary skill, and an integral part of social communication. It has been argued that the processing of faces is distinct from the processing of non-face stimuli and functional neuroimaging investigations have even found evidence of a distinction between the perception of faces and of emotional expressions. Structural and temporal correlates of face perception and facial affect have only been separately identified. Investigation neural dynamics of face perception per se as well as facial affect would allow the mapping of these in space, time and frequency specific domains. Participants were asked to perform face categorisation and emotional discrimination tasks and Magnetoencephalography (MEG) was used to measure the neurophysiology of face and facial emotion processing. SAM analysis techniques enable the investigation of spectral changes within specific time-windows and frequency bands, thus allowing the identification of stimulus specific regions of cortical power changes. Furthermore, MEG’s excellent temporal resolution allows for the detection of subtle changes associated with the processing of face and non-face stimuli and different emotional expressions. The data presented reveal that face perception is associated with spectral power changes within a distributed cortical network comprising occipito-temporal as well as parietal and frontal areas. For the perception of facial affect, spectral power changes were also observed within frontal and limbic areas including the parahippocampal gyrus and the amygdala. Analyses of temporal correlates also reveal a distinction between the processing of faces and facial affect. Face perception per se occurred at earlier latencies whereas the discrimination of facial expression occurred within a longer time-window. In addition, the processing of faces and facial affect was differentially associated with changes in cortical oscillatory power for alpha, beta and gamma frequencies. The perception of faces and facial affect is associated with distinct changes in cortical oscillatory activity that can be mapped to specific neural structures, specific time-windows and latencies as well as specific frequency bands. Therefore, the work presented in this thesis provides further insight into the sequential processing of faces and facial affect.

Elevated amygdala activity to sad facial expressions:a state marker of bipolar but not unipolar depression

Background - Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Methods - Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. Results - The BDd—relative to HC, BDr, and MDD—showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Conclusions - Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression.

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 influence of variations in eating disorder-related symptoms on processing of emotional faces in a non-clinical female sample:an eye-tracking study

This study aimed to: i) determine if the attention bias towards angry faces reported in eating disorders generalises to a non-clinical sample varying in eating disorder-related symptoms; ii) examine if the bias occurs during initial orientation or later strategic processing; and iii) confirm previous findings of impaired facial emotion recognition in non-clinical disordered eating. Fifty-two females viewed a series of face-pairs (happy or angry paired with neutral) whilst their attentional deployment was continuously monitored using an eye-tracker. They subsequently identified the emotion portrayed in a separate series of faces. The highest (n=18) and lowest scorers (n=17) on the Eating Disorders Inventory (EDI) were compared on the attention and facial emotion recognition tasks. Those with relatively high scores exhibited impaired facial emotion recognition, confirming previous findings in similar non-clinical samples. They also displayed biased attention away from emotional faces during later strategic processing, which is consistent with previously observed impairments in clinical samples. These differences were related to drive-for-thinness. Although we found no evidence of a bias towards angry faces, it is plausible that the observed impairments in emotion recognition and avoidance of emotional faces could disrupt social functioning and act as a risk factor for the development of eating disorders.

Coarse threat images reveal theta oscillations in the amygdala: a magnetoencephalography study

Neurocognitive models propose a specialized neural system for processing threat-related information, in which the amygdala plays a key role in the analysis of threat cues. fMRI research indicates that the amygdala is sensitive to coarse visual threat relevant information—for example, low spatial frequency (LSF) fearful faces. However, fMRI cannot determine the temporal or spectral characteristics of neural responses. Consequently, we used magnetoencephalography to explore spatiotemporal patterns of activity in the amygdala and cortical regions with blurry (LSF) and normal angry, fearful, and neutral faces. Results demonstrated differences in amygdala activity between LSF threat-related and LSF neutral faces (50-250 msec after face onset). These differences were evident in the theta range (4-8 Hz) and were accompanied by power changes within visual and frontal regions. Our results support the view that the amygdala is involved in the early processing of coarse threat related information and that theta is important in integrating activity within emotion-processing networks.

Short-term memory for emotional faces in dysphoria

The study aimed to determine if the memory bias for negative faces previously demonstrated in depression and dysphoria generalises from long- to short-term memory. A total of 29 dysphoric (DP) and22 non-dysphoric (ND) participants were presented with a series of faces and asked to identify the emotion portrayed (happiness, sadness, anger, or neutral affect). Following a delay, four faces were presented (the original plus three distractors) and participants were asked to identify the target face. Half of the trials assessed memory for facial emotion, and the remaining trials examined memory for facial identity. At encoding, no group differences were apparent. At memory testing, relative to ND participants, DP participants exhibited impaired memory for all types of facial emotion and for facial identity when the faces featured happiness, anger, or neutral affect, but not sadness. DP participants exhibited impaired identity memory for happy faces relative to angry, sad, and neutral, whereas ND participants exhibited enhanced facial identity memory when faces were angry. In general, memory for faces was not related to performance at encoding. However, in DP participants only, memory for sad faces was related to sadness recognition at encoding. The results suggest that the negative memory bias for faces in dysphoria does not generalise from long- to short-term memory.

Functional neuroimaging studies of bipolar disorder:examining the wide clinical spectrum in the search for disease endophenotypes

Bipolar disorder (BP) is among the top ten most disabling illnesses worldwide. This review includes findings from recent studies employing functional neuroimaging to examine functional abnormalities in neural systems underlying core domains of the psychopathology in BP: emotion processing, emotion regulation and executive control, and common comorbid features of BP, that are relevant to the wide spectrum of BP rather than focused on the more traditional BPI subtype, and that may facilitate future identification of diagnostically-relevant biomarkers of the disorder. In addition, an emerging number of studies are reviewed that demonstrate the use of neuroimaging to elucidate biomarkers whose identification may help to (1) identify at-risk individuals who will subsequently develop the illness to facilitate early intervention, (2) identify targets for treatment and markers of treatment response. The use of newer neuroimaging techniques and potential confounds of psychotropic medication upon neuroimaging findings in BP are also examined. These approaches will help to improve diagnosis and the mental well-being of all individuals with BP.

Sex differences in bipolar disorder:a review of neuroimaging findings and new evidence

Objectives: The sex of an individual is known to modulate the clinical presentation of bipolar disorder (BD), but little is known as to whether there are significant sex-by-diagnosis interactions on the brain structural and functional correlates of BD. Methods: We conducted a literature review of magnetic resonance imaging (MRI) studies in BD, published between January 1990 and December 2010, reporting on the effects of sex and diagnosis. In the absence of any functional MRI (fMRI) studies, this review was supplemented by original data analyses focusing on sex-by-diagnosis interactions on patterns of brain activation obtained during tasks of working memory, incentive decision-making, and facial affect processing. Results: We found no support for a sex-by-diagnosis interaction in global gray or white matter volume. Evidence regarding regional volumetric measures is limited, but points to complex interactions between sex and diagnosis with developmental and temperamental factors within limbic and prefrontal regions. Sex-by-diagnosis interactions were noted in the pattern of activation within the basal ganglia during incentive decision-making and within ventral prefrontal regions during facial affect processing. Conclusions: Potential sex-by-diagnosis interactions influencing the brain structural and functional correlates of disease expression in BD have received limited attention. Our data suggest that the sex of an individual modulates structure and function within subcortical and cortical regions implicated in disease expression. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Memory for emotional faces in major depression following judgement of physical facial characteristics at encoding

The aim of the present study was to establish if patients with major depression (MD) exhibit a memory bias for sad faces, relative to happy and neutral, when the affective element of the faces is not explicitly processed at encoding. To this end, 16 psychiatric out-patients with MD and 18 healthy, never-depressed controls (HC) were presented with a series of emotional faces and were required to identify the gender of the individuals featured in the photographs. Participants were subsequently given a recognition memory test for these faces. At encoding, patients with MD exhibited a non-significant tendency towards slower gender identification (GI) times, relative to HC, for happy faces. However, the GI times of the two groups did not differ for sad or neutral faces. At memory testing, patients with MD did not exhibit the expected memory bias for sad faces. Similarly, HC did not demonstrate enhanced memory for happy faces. Overall, patients with MD were impaired in their memory for the faces relative to the HC. The current findings are consistent with the proposal that mood-congruent memory biases are contingent upon explicit processing of the emotional element of the to-be-remembered material at encoding.