Jennifer C. Britton

Attention Bias Modification Treatment: A Meta-Analysis Toward the Establishment of Novel Treatment for Anxiety

BACKGROUND Attention Bias Modification Treatment (ABMT) is a newly emerging, promising treatment for anxiety disorders. Although recent randomized control trials (RCTs) suggest that ABMT reduces anxiety, therapeutic effects have not been summarized quantitatively. METHODS Standard meta-analytic procedures were used to summarize the effect of ABMT on anxiety. With MEDLINE, January 1995 to February 2010, we identified RCTs comparing the effects on anxiety of ABMT and quantified effect sizes with Hedges d. RESULTS Twelve studies met inclusion criteria, including 467 participants from 10 publications. Attention Bias Modification Treatment produced significantly greater reductions in anxiety than control training, with a medium effect (d = .51 [corrected] (p < .001). Age and gender did not moderate the effect of ABMT on anxiety, whereas several characteristics of the ABMT training did. CONCLUSIONS Attention Bias Modification Treatment shows promise as a novel treatment for anxiety. Additional RCTs are needed to fully evaluate the degree to which these findings replicate and apply to patients. Future work should consider the precise role for ABMT in the broader anxiety-disorder therapeutic armamentarium.

Neural correlates of individual ratings of emotional salience: A trial-related fMRI study

Accurate appraisal of meaningful environmental signals involves the interpretation of salient information for their intrinsic emotional value and personal relevance. We examined the neural basis for these components of endogenous salience during such appraisals using trial-related functional magnetic resonance imaging (fMRI). Subjects viewed affective pictures and assessed either the emotional intensity or extent of self-relatedness of the content of those pictures. In a parametric factorial design, individualized subjective ratings of these two dimensions were correlated with brain activity. The nucleus accumbens (NAcc) responded to both increasing emotional intensity and self-relatedness. Activity in the amygdala was specifically related to affective judgments and emotional intensity. The volitional act of appraising the extent of personal association specifically engaged the ventral medial prefrontal cortex (MPFC), and additionally recruited dorsal medial frontal regions and insula as the extent of self-relatedness increased. The findings highlight both overlapping and segregated neural representations of intrinsic value and personal relevance during the appraisal of emotional stimuli.

Facial expressions and complex IAPS pictures: common and differential networks.

Neuroimaging studies investigating emotion have commonly used two different visual stimulus formats, facial expressions of emotion or emotionally evocative scenes. However, it remains an important unanswered question whether or not these different stimulus formats entail the same processes. Facial expressions of emotion may elicit more emotion recognition/perception, and evocative pictures may elicit more direct experience of emotion. In spite of these differences, common areas of activation have been reported across different studies, but little work has investigated activations in response to the two stimulus formats in the same subjects. In this fMRI study, we compared BOLD activation patterns to facial expression of emotions and to complex emotional pictures from the International Affective Picture System (IAPS) to determine if these stimuli would activate similar or distinct brain regions. Healthy volunteers passively viewed blocks of expressive faces and IAPS pictures balanced for specific emotion (happy, sad, anger, fear, neutral), interleaved with blocks of fixation. Eye movement, reaction times, and off-line subjective ratings including discrete emotion, valence, and arousal were also recorded. Both faces and IAPS pictures activated similar structures, including the amygdala, posterior hippocampus, ventromedial prefrontal cortex, and visual cortex. In addition, expressive faces uniquely activated the superior temporal gyrus, insula, and anterior cingulate more than IAPS pictures, despite the faces being less arousing. For the most part, these regions were activated in response to all specific emotions; however, some regions responded only to a subset.

Neural correlates of social and nonsocial emotions: An fMRI study

Common theories of emotion emphasize valence and arousal dimensions or alternatively, specific emotions, and the search for the underlying neurocircuitry is underway. However, it is likely that other important dimensions for emotional neurocircuitry exist, and one of them is sociality. A social dimension may code whether emotions are addressing an individuals biological/visceral need versus more remote social goals involving semantic meaning or intentionality. Thus, for practical purposes, social emotions may be distinguished from nonsocial emotions based in part on the presence of human forms. In the current fMRI study, we aimed to compare regional coding of the sociality dimension of emotion (nonsocial versus social) versus the valence dimension of emotion (positive versus negative). Using a novel fMRI paradigm, film and picture stimuli were combined to induce and maintain four emotions varying along social and valence dimensions. Nonsocial emotions of positively valenced appetite and negatively valenced disgust and social emotions of positively valenced joy/amusement and negatively valenced sadness were studied. All conditions activated the thalamus. Appetite and disgust activated posterior insula and visual cortex, whereas joy/amusement and sadness activated extended amygdala, superior temporal gyrus, hippocampus, and posterior cingulate. Activations within the anterior cingulate, nucleus accumbens, orbitofrontal cortex, and amygdala were modulated by both social and valence dimensions. Overall, these findings highlight that sociality has a key role in processing emotional valence, which may have implications for patient populations with social and emotional deficits.

Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery

BACKGROUND Functional neuroimaging experiments targeting personal recall of emotional events may help elucidate neural substrates underlying posttraumatic stress disorder (PTSD). Studies suggest that limbic and paralimbic function might be altered in PTSD, as compared with trauma-exposed control subjects; however, little is known about functional changes resulting from traumatic experience itself. The present study examined both PTSD-specific and trauma-specific regional cerebral blood flow (rCBF) patterns during script-driven imagery. METHODS Sixteen combat veterans with PTSD (PP); 15 combat veterans without PTSD (CC); and 14 healthy, aged-matched noncombat control subjects (NC) underwent [15O] H20 positron emission tomography (PET) scanning during script-driven imagery of emotionally evocative and neutral autobiographic events. RESULTS Differential patterns of activation were detected in amygdala and medial frontal cortex. Past trauma experience was associated with decreased amygdala activity (i.e., less activity than healthy control subjects); however, combat control subjects deactivated this region (i.e., greater activity to neutral scripts). All subjects deactivated medial frontal cortex; PTSD patients had greater rostral anterior cingulate (rACC) deactivation compared with control groups, who deactivated ventromedial prefrontal cortex (vmPFC). CONCLUSIONS Trauma-specific patterns may represent potential compensatory changes to traumatic reminders, while patterns observed only in the PTSD group may reflect neural substrates specific to PTSD pathophysiology.

Activation of the medial prefrontal cortex and extended amygdala by individual ratings of emotional arousal: a fMRI study

BACKGROUND Significant differences between individual responses to emotional stimuli can be important for the study of emotion. We investigated whether incorporating individual ratings of emotional arousal in the analysis of functional magnetic resonance imaging (fMRI) data improves the detection of activation in the medial prefrontal cortex (MPFC) and sublenticular extended amygdala (SLEA), areas implicated in the processing of emotional salience. METHODS Healthy subjects viewed counterbalanced blocks of aversive, nonaversive, and blank images. Outside the scanner, they rated the intensity of emotional arousal (salience) of each presented picture. RESULTS Incorporating the subjects response to each stimulus by using individualized regressors produced more robust activations within MPFC and SLEA compared with a simple boxcar regressor, identical for all subjects. CONCLUSIONS Our findings demonstrate that individual behavioral data are useful in improving detection of activation in block-design functional imaging studies.

Neural response to emotional salience in schizophrenia

Neuroimaging probes of brain regions implicated in emotion represent an important research strategy for understanding emotional dysfunction in schizophrenia. Anterior limbic structures, such as the ventral striatum and the amygdala, have been implicated in the pathophysiology of schizophrenia and the generation of emotional responses, although few studies to date have used emotion probes to target these areas in schizophrenia. With this goal in mind, emotionally salient visual images were used in a simple, nondemanding task. In all, 13 medicated, schizophrenic patients, five unmedicated patients, and 10 healthy volunteers viewed complex visual pictures and a nonsalient, blank screen while regional cerebral blood flow was measured with the [O–15] water technique. Pictures consisted of real world scenes with aversive, positive, and nonaversive content. Eye movements were recorded simultaneous with scan acquisition. Positron emission tomography images were analyzed for baseline, tonic activity, in addition to phasic changes (‘activation’) to salient stimuli. Lateral eye movement measures and on-line ratings showed good behavioral compliance with the task. Patients with schizophrenia showed impaired neural responses to salient stimuli in the right ventral striatum (VS), and they exhibited elevated tonic activity levels in the right VS and bilateral amygdala, inversely correlated with overall symptom severity. The patients also showed reduced modulation of visual cortex by salient stimuli. The results show that patients with schizophrenia exhibit impaired neural responses to emotionally salient stimuli in the VS, supporting a role for this structure in the pathophysiology of the illness. Reduced modulation of visual cortex by emotionally salient stimuli also suggests a failure to organize cerebral activity at a global level.

Linear mixed-effects modeling approach to FMRI group analysis

Conventional group analysis is usually performed with Student-type t-test, regression, or standard AN(C)OVA in which the variance-covariance matrix is presumed to have a simple structure. Some correction approaches are adopted when assumptions about the covariance structure is violated. However, as experiments are designed with different degrees of sophistication, these traditional methods can become cumbersome, or even be unable to handle the situation at hand. For example, most current FMRI software packages have difficulty analyzing the following scenarios at group level: (1) taking within-subject variability into account when there are effect estimates from multiple runs or sessions; (2) continuous explanatory variables (covariates) modeling in the presence of a within-subject (repeated measures) factor, multiple subject-grouping (between-subjects) factors, or the mixture of both; (3) subject-specific adjustments in covariate modeling; (4) group analysis with estimation of hemodynamic response (HDR) function by multiple basis functions; (5) various cases of missing data in longitudinal studies; and (6) group studies involving family members or twins. Here we present a linear mixed-effects modeling (LME) methodology that extends the conventional group analysis approach to analyze many complicated cases, including the six prototypes delineated above, whose analyses would be otherwise either difficult or unfeasible under traditional frameworks such as AN(C)OVA and general linear model (GLM). In addition, the strength of the LME framework lies in its flexibility to model and estimate the variance-covariance structures for both random effects and residuals. The intraclass correlation (ICC) values can be easily obtained with an LME model with crossed random effects, even at the presence of confounding fixed effects. The simulations of one prototypical scenario indicate that the LME modeling keeps a balance between the control for false positives and the sensitivity for activation detection. The importance of hypothesis formulation is also illustrated in the simulations. Comparisons with alternative group analysis approaches and the limitations of LME are discussed in details.

Habituation of rostral anterior cingulate cortex to repeated emotionally salient pictures.

Habituation of the neural response to repeated stimuli has been well demonstrated for subcortical limbic regions responding to emotionally salient stimuli. Although the rostral or affective division of the anterior cingulate cortex (rACC) is also engaged during emotional processing, little is known about the temporal dynamics of this region in sustained evaluation of emotional salience. Using a test/retest design, the present study assessed habituation in the human brain with functional magnetic resonance imaging. Eight healthy subjects were exposed to two repeated runs of aversive, neutral, and blank images. Activation of the rACC to negatively valenced pictures occurred only in the first session, and this activation was significantly greater in the first relative to the second session. Additionally, medial prefrontal cortex, hippocampal, and amygdalar activations were noted during the first, but not second, presentation of aversive pictures. These findings highlight the phasic activity of the rACC in emotional processing consistent with habituation.

Distinct neural signatures of threat learning in adolescents and adults

Most teenage fears subside with age, a change that may reflect brain maturation in the service of refined fear learning. Whereas adults clearly demarcate safe situations from real dangers, attenuating fear to the former but not the latter, adolescents’ immaturity in prefrontal cortex function may limit their ability to form clear-cut threat categories, allowing pervasive fears to manifest. Here we developed a discrimination learning paradigm that assesses the ability to categorize threat from safety cues to test these hypotheses on age differences in neurodevelopment. In experiment 1, we first demonstrated the capacity of this paradigm to generate threat/safety discrimination learning in both adolescents and adults. Next, in experiment 2, we used this paradigm to compare the behavioral and neural correlates of threat/safety discrimination learning in adolescents and adults using functional MRI. This second experiment yielded three sets of findings. First, when labeling threats online, adolescents reported less discrimination between threat and safety cues than adults. Second, adolescents were more likely than adults to engage early-maturing subcortical structures during threat/safety discrimination learning. Third, adults’ but not adolescents’ engagement of late-maturing prefrontal cortex regions correlated positively with fear ratings during threat/safety discrimination learning. These data are consistent with the role of dorsolateral regions during category learning, particularly when differences between stimuli are subtle [Miller EK, Cohen JD (2001) Annu Rev Neurosci 24:167–202]. These findings suggest that maturational differences in subcortical and prefrontal regions between adolescent and adult brains may relate to age-related differences in threat/safety discrimination.