The Influence of a Working Memory Task on Affective Perception of Facial Expressions

In a dual-task paradigm, participants performed a spatial location working memory task and a forced two-choice perceptual decision task (neutral vs. fearful) with gradually morphed emotional faces (neutral ∼ fearful). Task-irrelevant word distractors (negative, neutral, and control) were experimentally manipulated during spatial working memory encoding. We hypothesized that, if affective perception is influenced by concurrent cognitive load using a working memory task, task-irrelevant emotional distractors would bias subsequent perceptual decision-making on ambiguous facial expression. We found that when either neutral or negative emotional words were presented as task-irrelevant working-memory distractors, participants more frequently reported fearful face perception - but only at the higher emotional intensity levels of morphed faces. Also, the affective perception bias due to negative emotional distractors correlated with a decrease in working memory performance. Taken together, our findings suggest that concurrent working memory load by task-irrelevant distractors has an impact on affective perception of facial expressions.     

Functional neuronal network activity differs with cognitive dysfunction in childhood-onset systemic lupus erythematosus

Introduction

Neuropsychiatric manifestations are common in childhood-onset systemic lupus erythematosus (cSLE) and often include neurocognitive dysfunction (NCD). Functional magnetic resonance imaging (fMRI) can measure brain activation during tasks that invoke domains of cognitive function impaired by cSLE. This study investigates specific changes in brain function attributable to NCD in cSLE that have potential to serve as imaging biomarkers.

Methods

Formal neuropsychological testing was done to measure cognitive ability and to identify NCD. Participants performed fMRI tasks probing three cognitive domains impacted by cSLE: visuoconstructional ability (VCA), working memory, and attention. Imaging data, collected on 3-Tesla scanners, included a high-resolution T1-weighted anatomic reference image followed by a T2*-weighted whole-brain echo planar image series for each fMRI task. Brain activation using blood oxygenation level-dependent contrast was compared between cSLE patients with NCD (NCD-group, n = 7) vs. without NCD (noNCD-group, n = 14) using voxel-wise and region of interest-based analyses. The relationship of brain activation during fMRI tasks and performance in formal neuropsychological testing was assessed.

Results

Greater brain activation was observed in the noNCD-group vs. NCD-group during VCA and working memory fMRI tasks. Conversely, compared to the noNCD-group, the NCD-group showed more brain activation during the attention fMRI task. In region of interest analysis, brain activity during VCA and working memory fMRI tasks was positively associated with the participants'' neuropsychological test performance. In contrast, brain activation during the attention fMRI task was negatively correlated with neuropsychological test performance. While the NCD group performed worse than the noNCD group during VCA and working memory tasks, the attention task was performed equally well by both groups.

Conclusions

NCD in patients with cSLE is characterized by differential activation of functional neuronal networks during fMRI tasks probing working memory, VCA, and attention. Results suggest a compensatory mechanism allows maintenance of attentional performance under NCD. This mechanism appears to break down for the VCA and working memory challenges presented in this study. The observation that neuronal network activation is related to the formal neuropsychological testing performance makes fMRI a candidate imaging biomarker for cSLE-associated NCD.     

Anterior medial prefrontal cortex exhibits activation during task preparation but deactivation during task execution

Background

The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task.

Methodology/Principal Findings

Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial.

Conclusions/Significance

The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing.     

Effects of attention and emotion on face processing in the human brain: an event-related fMRI study.

We used event-related fMRI to assess whether brain responses to fearful versus neutral faces are modulated by spatial attention. Subjects performed a demanding matching task for pairs of stimuli at prespecified locations, in the presence of task-irrelevant stimuli at other locations. Faces or houses unpredictably appeared at the relevant or irrelevant locations, while the faces had either fearful or neutral expressions. Activation of fusiform gyri by faces was strongly affected by attentional condition, but the left amygdala response to fearful faces was not. Right fusiform activity was greater for fearful than neutral faces, independently of the attention effect on this region. These results reveal differential influences on face processing from attention and emotion, with the amygdala response to threat-related expressions unaffected by a manipulation of attention that strongly modulates the fusiform response to faces.     

Increased memory load-related frontal activation after estradiol treatment in postmenopausal women

Prior research shows that menopause is associated with changes in cognition in some older women. However, how estrogen loss and subsequent estrogen treatment affects cognition and particularly the underlying brain processes responsible for any cognitive changes is less well understood. We examined the ability of estradiol to modulate the manipulation of information in working memory and related brain activation in postmenopausal women. Twenty healthy postmenopausal women (mean age (SD) = 59.13 (5.5)) were randomly assigned to three months of 1 mg oral 17-β estradiol or placebo. At baseline and three months later each woman completed a visual verbal N-back sequential letter test of working memory during functional magnetic resonance imaging (fMRI). The fMRI data showed that women who were treated with estradiol for three months had increased frontal activation during the more difficult working memory load conditions compared to women treated with placebo. Performance on the verbal working memory task showed no difference between estradiol and placebo treated subjects. These data are consistent with prior work showing increases in frontal activation on memory tasks after estrogen treatment. However, this is the first study to show that estrogen-induced increases in brain activity were tied to cognitive load during a verbal working memory task. These data suggest that estradiol treatment effects on cognition may be in part produced through modulation of frontal lobe functioning under difficult task conditions.     

Effects of AKAP5 Pro100Leu Genotype on Working Memory for Emotional Stimuli

Recent investigations addressing the role of the synaptic multiadaptor molecule AKAP5 in human emotion and behavior suggest that the AKAP5 Pro100Leu polymorphism (rs2230491) contributes to individual differences in affective control. Carriers of the less common Leu allele show a higher control of anger as indicated by behavioral measures and dACC brain response on emotional distracters when compared to Pro homozygotes. In the current fMRI study we used an emotional working memory task according to the n-back scheme with neutral and negative emotional faces as target stimuli. Pro homozygotes showed a performance advantage at the behavioral level and exhibited enhanced activation of the amygdala and fusiform face area during working memory for emotional faces. On the other hand, Leu carriers exhibited increased activation of the dACC during performance of the 2-back condition. Our results suggest that AKAP5 Pro100Leu effects on emotion processing might be task-dependent with Pro homozygotes showing lower control of emotional interference, but more efficient processing of task-relevant emotional stimuli.     

Working memory in attention deficit/hyperactivity disorder is characterized by a lack of specialization of brain function

Working memory impairments are frequent in Attention Deficit/Hyperactivity Disorder (ADHD) and create problems along numerous functional dimensions. The present study utilized the Visual Serial Addition Task (VSAT) and functional magnetic resonance imaging (fMRI) to explore working memory processes in thirteen typically developing (TD) control and thirteen children with ADHD, Combined type. Analysis of Variance (ANOVA) was used to examine both main effects and interactions. Working memory-specific activity was found in TD children in the bilateral prefrontal cortex. In contrast the within-group map in ADHD did not reveal any working-memory specific regions. Main effects of condition suggested that the right middle frontal gyrus (BA6) and the right precuneus were engaged by both groups during working memory processing. Group differences were driven by significantly greater, non-working memory-specific, activation in the ADHD relative to TD group in the bilateral insula extending into basal ganglia and the medial prefrontal cortex. A region of interest analysis revealed a region in left middle frontal gyrus that was more active during working memory in TD controls. Thus, only the TD group appeared to display working memory-modulated brain activation. In conclusion, children with ADHD demonstrated reduced working memory task specific brain activation in comparison to their peers. These data suggest inefficiency in functional recruitment by individuals with ADHD represented by a poor match between task demands and appropriate levels of brain activity.     

Reduced Functional Reserve in Patients with Age-Related White Matter Changes: A Preliminary fMRI Study of Working Memory

Subcortical age-related white matter changes (ARWMC) are a frequent finding in healthy elderly people suggested to cause secondary tissue changes and possibly affecting cognitive processes. We aimed to determine the influence of the extent of ARWMC load on attention and working memory processes in healthy elderly individuals. Fourteen healthy elderly subjects (MMSE >26; age 55–80 years) performed three fMRI tasks with increasing difficulty assessing alertness, attention (0-back), and working memory (2-back). We compared activation patterns in those with only minimal ARWMC (Fazekas 0–1) to those with moderate to severe ARWMC (Fazekas 2–3). During the fMRI experiments, the study population showed activation in brain areas typically involved in attention and working memory with a recruitment of cortical areas with increasing task difficulty. Subjects with higher lesion load showed a higher activation at all task levels with only sparse increase of signal with increasing complexity. In the lower lesion load group, rising task difficulty lead to a significant and widely distributed increase of activation. Although the number of patients included in the study is small, these findings suggest that even clinically silent ARWMC may affect cognitive processing and lead to compensatory activation during cognitive tasks. This can be interpreted as a reduction of functional reserve and may pose a risk for cognitive decline in these patients.     

Increased memory load-related frontal activation after estradiol treatment in postmenopausal women

Prior research shows that menopause is associated with changes in cognition in some older women. However, how estrogen loss and subsequent estrogen treatment affects cognition and particularly the underlying brain processes responsible for any cognitive changes is less well understood. We examined the ability of estradiol to modulate the manipulation of information in working memory and related brain activation in postmenopausal women. Twenty healthy postmenopausal women (mean age (SD) = 59.13 (5.5)) were randomly assigned to three months of 1 mg oral 17-β estradiol or placebo. At baseline and three months later each woman completed a visual verbal N-back sequential letter test of working memory during functional magnetic resonance imaging (fMRI). The fMRI data showed that women who were treated with estradiol for three months had increased frontal activation during the more difficult working memory load conditions compared to women treated with placebo. Performance on the verbal working memory task showed no difference between estradiol and placebo treated subjects. These data are consistent with prior work showing increases in frontal activation on memory tasks after estrogen treatment. However, this is the first study to show that estrogen-induced increases in brain activity were tied to cognitive load during a verbal working memory task. These data suggest that estradiol treatment effects on cognition may be in part produced through modulation of frontal lobe functioning under difficult task conditions.     

Cerebral Inefficient Activation in Schizophrenia Patients and Their Unaffected Parents during the N-Back Working Memory Task: A Family fMRI Study

Background

It has been suggested that working memory deficits is a core feature of symptomatology of schizophrenia, which can be detected in patients and their unaffected relatives. The impairment of working memory has been found related to the abnormal activity of human brain regions in many functional magnetic resonance imaging (fMRI) studies. This study investigated how brain region activation was altered in schizophrenia and how it was inherited independently from performance deficits.

Method

The authors used fMRI method during N-back task to assess working memory related cortical activation in four groups (N = 20 in each group, matching task performance, age, gender and education): schizophrenic patients, their unaffected biological parents, young healthy controls for the patients and older healthy controls for their parents.

Results

Compared to healthy controls, patients showed an exaggerated response in the right dorsolateral prefrontal cortex (brodmann area [BA] 46) and bilateral ventrolateral prefrontal cortex, and had reduced activation in bilateral dorsolateral prefrontal cortex (BA 9). In the conjunction analysis, the effect of genetic risk (parents versus older control) shared significantly overlapped activation with effect of disease (patients versus young control) in the right middle frontal gyrus (BA 46) and left inferior parietal gyrus (BA 40).

Conclusions

Physiological inefficiency of dorsal prefrontal cortex and compensation involvement of ventral prefrontal cortex in working memory function may one physiological characteristics of schizophrenia. And relatively inefficient activation in dorsolateral prefrontal cortex probably can be a promising intermediate phenotype for schizophrenia.     

Asymmetrical activation in the human brain during processing of fearful faces

Traditional split-field studies and patient research indicate a privileged role for the right hemisphere in emotional processing [1-7], but there has been little direct fMRI evidence for this, despite many studies on emotional-face processing [8-10](see Supplemental Background). With fMRI, we addressed differential hemispheric processing of fearful versus neutral faces by presenting subjects with faces bilaterally [11-13]and orthogonally manipulating whether each hemifield showed a fearful or neutral expression prior to presentation of a checkerboard target. Target discrimination in the left visual field was more accurate after a fearful face was presented there. Event-related fMRI showed right-lateralized brain activations for fearful minus neutral left-hemifield faces in right visual areas, as well as more activity in the right than in the left amygdala. These activations occurred regardless of the type of right-hemifield face shown concurrently, concordant with the behavioral effect. No analogous behavioral or fMRI effects were observed for fearful faces in the right visual field (left hemisphere). The amygdala showed enhanced functional coupling with right-middle and anterior-fusiform areas in the context of a left-hemifield fearful face. These data provide behavioral and fMRI evidence for right-lateralized emotional processing during bilateral stimulation involving enhanced coupling of the amygdala and right-hemispheric extrastriate cortex.     

Discriminating grotesque from typical faces: evidence from the Thatcher illusion

The discrimination of thatcherized faces from typical faces was explored in two simultaneous alternative forced choice tasks. Reaction times (RTs) and errors were measured in a behavioural task. Brain activation was measured in an equivalent fMRI task. In both tasks, participants were tested with upright and inverted faces. Participants were also tested on churches in the behavioural task. The behavioural task confirmed the face specificity of the illusion (by comparing inversion effects for faces against churches) but also demonstrated that the discrimination was primarily, although not exclusively, driven by attending to eyes. The fMRI task showed that, relative to inverted faces, upright grotesque faces are discriminated via activation of a network of emotion/social evaluation processing areas. On the other hand, discrimination of inverted thatcherized faces was associated with increased activation of brain areas that are typically involved in perceptual processing of faces.     

Frontal EEG Activation Asymmetry Reflects Cognitive Biases in Anxiety: Evidence from an Emotional Face Stroop Task

Electroencephalography (EEG) has been extensively used in studies of the frontal asymmetry of emotion and motivation. This study investigated the midfrontal EEG activation, heart rate and skin conductance during an emotional face analog of the Stroop task, in anxious and non-anxious participants. In this task, the participants were asked to identify the expression of calm, fearful and happy faces that had either a congruent or incongruent emotion name written across them. Anxious participants displayed a cognitive bias characterized by facilitated attentional engagement with fearful faces. Fearful face trials induced greater relative right frontal activation, whereas happy face trials induced greater relative left frontal activation. Moreover, anxiety specifically modulated the magnitude of the right frontal activation to fearful faces, which also correlated with the cognitive bias. Therefore, these results show that frontal EEG activation asymmetry reflects the bias toward facilitated processing of fearful faces in anxiety.     

Diminished Activation of Motor Working-Memory Networks in Parkinson's Disease

Parkinson''s disease (PD) is characterized by typical extrapyramidal motor features and increasingly recognized non-motor symptoms such as working memory (WM) deficits. Using functional magnetic resonance imaging (fMRI), we investigated differences in neuronal activation during a motor WM task in 23 non-demented PD patients and 23 age- and gender-matched healthy controls. Participants had to memorize and retype variably long visuo-spatial stimulus sequences after short or long delays (immediate or delayed serial recall). PD patients showed deficient WM performance compared to controls, which was accompanied by reduced encoding-related activation in WM-related regions. Mirroring slower motor initiation and execution, reduced activation in motor structures such as the basal ganglia and superior parietal cortex was detected for both immediate and delayed recall. Increased activation in limbic, parietal and cerebellar regions was found during delayed recall only. Increased load-related activation for delayed recall was found in the posterior midline and the cerebellum. Overall, our results demonstrate that impairment of WM in PD is primarily associated with a widespread reduction of task-relevant activation, whereas additional parietal, limbic and cerebellar regions become more activated relative to matched controls. While the reduced WM-related activity mirrors the deficient WM performance, the additional recruitment may point to either dysfunctional compensatory strategies or detrimental crosstalk from “default-mode” regions, contributing to the observed impairment.     

Effects on Automatic Attention Due to Exposure to Pictures of Emotional Faces while Performing Chinese Word Judgment Tasks

Two experiments were conducted to investigate the automatic processing of emotional facial expressions while performing low or high demand cognitive tasks under unattended conditions. In Experiment 1, 35 subjects performed low (judging the structure of Chinese words) and high (judging the tone of Chinese words) cognitive load tasks while exposed to unattended pictures of fearful, neutral, or happy faces. The results revealed that the reaction time was slower and the performance accuracy was higher while performing the low cognitive load task than while performing the high cognitive load task. Exposure to fearful faces resulted in significantly longer reaction times and lower accuracy than exposure to neutral faces on the low cognitive load task. In Experiment 2, 26 subjects performed the same word judgment tasks and their brain event-related potentials (ERPs) were measured for a period of 800 ms after the onset of the task stimulus. The amplitudes of the early component of ERP around 176 ms (P2) elicited by unattended fearful faces over frontal-central-parietal recording sites was significantly larger than those elicited by unattended neutral faces while performing the word structure judgment task. Together, the findings of the two experiments indicated that unattended fearful faces captured significantly more attention resources than unattended neutral faces on a low cognitive load task, but not on a high cognitive load task. It was concluded that fearful faces could automatically capture attention if residues of attention resources were available under the unattended condition.     

Emotion-Motion Interactions in Conversion Disorder: An fMRI Study

Objectives

To evaluate the neural correlates of implicit processing of negative emotions in motor conversion disorder (CD) patients.

Methods

An event related fMRI task was completed by 12 motor CD patients and 14 matched healthy controls using standardised stimuli of faces with fearful and sad emotional expressions in comparison to faces with neutral expressions. Temporal changes in the sensitivity to stimuli were also modelled and tested in the two groups.

Results

We found increased amygdala activation to negative emotions in CD compared to healthy controls in region of interest analyses, which persisted over time consistent with previous findings using emotional paradigms. Furthermore during whole brain analyses we found significantly increased activation in CD patients in areas involved in the ‘freeze response’ to fear (periaqueductal grey matter), and areas involved in self-awareness and motor control (cingulate gyrus and supplementary motor area).

Conclusions

In contrast to healthy controls, CD patients exhibited increased response amplitude to fearful stimuli over time, suggesting abnormal emotional regulation (failure of habituation / sensitization). Patients with CD also activated midbrain and frontal structures that could reflect an abnormal behavioral-motor response to negative including threatening stimuli. This suggests a mechanism linking emotions to motor dysfunction in CD.     

Origins of spatial working memory deficits in schizophrenia: an event-related FMRI and near-infrared spectroscopy study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased 'false memory' errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased "false memory" errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research.     

Stability of Whole Brain and Regional Network Topology within and between Resting and Cognitive States

Background

Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI) data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well.

Methodology/Principal Findings

fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state.

Conclusions/Significance

These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.     

Cortical responses to invisible faces: dissociating subsystems for facial-information processing

Perceiving faces is critical for social interaction. Evidence suggests that different neural pathways may be responsible for processing face identity and expression information. By using functional magnetic resonance imaging (fMRI), we measured brain responses when observers viewed neutral, fearful, and scrambled faces, either visible or rendered invisible through interocular suppression. The right fusiform face area (FFA), the right superior temporal sulcus (STS), and the amygdala responded strongly to visible faces. However, when face images became invisible, activity in FFA to both neutral and fearful faces was much reduced, although still measurable; activity in the STS was robust only to invisible fearful faces but not to neutral faces. Activity in the amygdala was equally strong in both the visible and invisible conditions to fearful faces but much weaker in the invisible condition for the neutral faces. In the invisible condition, amygdala activity was highly correlated with that of the STS but not with FFA. The results in the invisible condition support the existence of dissociable neural systems specialized for processing facial identity and expression information. When images are invisible, cortical responses may reflect primarily feed-forward visual-information processing and thus allow us to reveal the distinct functions of FFA and STS.