Tor D. Wager

Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI.

Neuroimagingstudies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have begun to describe the functional neuroanatomy of emotion. Taken separately, specific studies vary in task dimensions and in type(s) of emotion studied and are limited by statistical power and sensitivity. By examining findings across studies, we sought to determine if common or segregated patterns of activations exist across various emotional tasks. We reviewed 55 PET and fMRI activation studies (yielding 761 individual peaks) which investigated emotion in healthy subjects. Peak activation coordinates were transformed into a standard space and plotted onto canonical 3-D brain renderings. We divided the brain into 20 nonoverlapping regions, and characterized each region by its responsiveness across individual emotions (positive, negative, happiness, fear, anger, sadness, disgust), to different induction methods (visual, auditory, recall/imagery), and in emotional tasks with and without cognitive demand. Our review yielded the following summary observations: (1) The medial prefrontal cortex had a general role in emotional processing; (2) fear specifically engaged the amygdala; (3) sadness was associated with activity in the subcallosal cingulate; (4) emotional induction by visual stimuli activated the occipital cortex and the amygdala; (5) induction by emotional recall/imagery recruited the anterior cingulate and insula; (6) emotional tasks with cognitive demand also involved the anterior cingulate and insula. This review provides a critical comparison of findings across individual studies and suggests that separate brain regions are involved in different aspects of emotion.

Valid conjunction inference with the minimum statistic.

In logic a conjunction is defined as an AND between truth statements. In neuroimaging, investigators may look for brain areas activated by task A AND by task B, or a conjunction of tasks (Price, C.J., Friston, K.J., 1997. Cognitive conjunction: a new approach to brain activation experiments. NeuroImage 5, 261-270). Friston et al. (Friston, K., Holmes, A., Price, C., Buchel, C., Worsley, K., 1999. Multisubject fMRI studies and conjunction analyses. NeuroImage 10, 85-396) introduced a minimum statistic test for conjunction. We refer to this method as the minimum statistic compared to the global null (MS/GN). The MS/GN is implemented in SPM2 and SPM99 software, and has been widely used as a test of conjunction. However, we assert that it does not have the correct null hypothesis for a test of logical AND, and further, this has led to confusion in the neuroimaging community. In this paper, we define a conjunction and explain the problem with the MS/GN test as a conjunction method. We present a survey of recent practice in neuroimaging which reveals that the MS/GN test is very often misinterpreted as evidence of a logical AND. We show that a correct test for a logical AND requires that all the comparisons in the conjunction are individually significant. This result holds even if the comparisons are not independent. We suggest that the revised test proposed here is the appropriate means for conjunction inference in neuroimaging.

Neuroimaging studies of working memory: a meta-analysis.

We performed meta-analyses on 60 neuroimaging (PET and fMRI) studies of working memory (WM), considering three types of storage material (spatial, verbal, and object), three types of executive function (continuous updating of WM, memory for temporal order, and manipulation of information in WM), and interactions between material and executive function. Analyses of material type showed the expected dorsal-ventral dissociation between spatial and nonspatial storage in the posterior cortex, but not in the frontal cortex. Some support was found for left frontal dominance in verbal WM, but only for tasks with low executive demand. Executive demand increased right lateralization in the frontal cortex for spatial WM. Tasks requiring executive processing generally produce more dorsal frontal activations than do storage-only tasks, but not all executive processes show this pattern. Brodmann’s areas (BAs) 6, 8, and 9, in the superior frontal cortex, respond most when WM must be continuously updated and when memory for temporal order must be maintained. Right BAs 10 and 47, in the ventral frontal cortex, respond more frequently with demand for manipulation (including dual-task requirements or mental operations). BA 7, in the posterior parietal cortex, is involved in all types of executive function. Finally, we consider a potential fourth executive function: selective attention to features of a stimulus to be stored in WM, which leads to increased probability of activating the medial prefrontal cortex (BA 32) in storage tasks.

Prefrontal-Subcortical Pathways Mediating Successful Emotion Regulation

Although prefrontal cortex has been implicated in the cognitive regulation of emotion, the cortical-subcortical interactions that mediate this ability remain poorly understood. To address this issue, we identified a right ventrolateral prefrontal region (vlPFC) whose activity correlated with reduced negative emotional experience during cognitive reappraisal of aversive images. We then applied a pathway-mapping analysis on subcortical regions to locate mediators of the association between vlPFC activity and reappraisal success (i.e., reductions in reported emotion). Results identified two separable pathways that together explained approximately 50% of the reported variance in self-reported emotion: (1) a path through nucleus accumbens that predicted greater reappraisal success, and (2) a path through ventral amygdala that predicted reduced reappraisal success (i.e., more negative emotion). These results provide direct evidence that vlPFC is involved in both the generation and regulation of emotion through different subcortical pathways, suggesting a general role for this region in appraisal processes.

Valence, gender, and lateralization of functional brain anatomy in emotion: a meta-analysis of findings from neuroimaging

We performed quantitative meta-analyses on 65 neuroimaging studies of emotion. In an earlier report (NeuroImage 16 (2002), 331). we examined the effects of induction method, specific emotions, and cognitive demand in emotional tasks. This paper focuses on the effects of emotional valence (positive vs negative and approach vs withdrawal) and gender on regional brain activations, with particular emphasis on hypotheses concerning lateralization of brain function in emotion. Overall, we found no support for the hypothesis of overall right-lateralization of emotional function, and limited support for valence-specific lateralization of emotional activity in frontal cortex. In addition, we found that males showed more lateralization of emotional activity, and females showed more brainstem activation in affective paradigms. The study provides evidence that lateralization of emotional activity is more complex and region-specific than predicted by previous theories of emotion and the brain.

The brain basis of emotion: A meta-analytic review

Researchers have wondered how the brain creates emotions since the early days of psychological science. With a surge of studies in affective neuroscience in recent decades, scientists are poised to answer this question. In this target article, we present a meta-analytic summary of the neuroimaging literature on human emotion. We compare the locationist approach (i.e., the hypothesis that discrete emotion categories consistently and specifically correspond to distinct brain regions) with the psychological constructionist approach (i.e., the hypothesis that discrete emotion categories are constructed of more general brain networks not specific to those categories) to better understand the brain basis of emotion. We review both locationist and psychological constructionist hypotheses of brain-emotion correspondence and report meta-analytic findings bearing on these hypotheses. Overall, we found little evidence that discrete emotion categories can be consistently and specifically localized to distinct brain regions. Instead, we found evidence that is consistent with a psychological constructionist approach to the mind: A set of interacting brain regions commonly involved in basic psychological operations of both an emotional and non-emotional nature are active during emotion experience and perception across a range of discrete emotion categories.

Cognitive Reappraisal of Emotion: A Meta-Analysis of Human Neuroimaging Studies

In recent years, an explosion of neuroimaging studies has examined cognitive reappraisal, an emotion regulation strategy that involves changing the way one thinks about a stimulus in order to change its affective impact. Existing models broadly agree that reappraisal recruits frontal and parietal control regions to modulate emotional responding in the amygdala, but they offer competing visions of how this is accomplished. One view holds that control regions engage ventromedial prefrontal cortex (vmPFC), an area associated with fear extinction, that in turn modulates amygdala responses. An alternative view is that control regions modulate semantic representations in lateral temporal cortex that indirectly influence emotion-related responses in the amygdala. Furthermore, while previous work has emphasized the amygdala, whether reappraisal influences other regions implicated in emotional responding remains unknown. To resolve these questions, we performed a meta-analysis of 48 neuroimaging studies of reappraisal, most involving downregulation of negative affect. Reappraisal consistently 1) activated cognitive control regions and lateral temporal cortex, but not vmPFC, and 2) modulated the bilateral amygdala, but no other brain regions. This suggests that reappraisal involves the use of cognitive control to modulate semantic representations of an emotional stimulus, and these altered representations in turn attenuate activity in the amygdala.

Neurobiological Mechanisms of the Placebo Effect

Any medical treatment is surrounded by a psychosocial context that affects the therapeutic outcome. If we want to study this psychosocial context, we need to eliminate the specific action of a therapy and to simulate a context that is similar in all respects to that of a real treatment. To do this,

An fMRI-Based Neurologic Signature of Physical Pain

BACKGROUND Persistent pain is measured by means of self-report, the sole reliance on which hampers diagnosis and treatment. Functional magnetic resonance imaging (fMRI) holds promise for identifying objective measures of pain, but brain measures that are sensitive and specific to physical pain have not yet been identified. METHODS In four studies involving a total of 114 participants, we developed an fMRI-based measure that predicts pain intensity at the level of the individual person. In study 1, we used machine-learning analyses to identify a pattern of fMRI activity across brain regions--a neurologic signature--that was associated with heat-induced pain. The pattern included the thalamus, the posterior and anterior insulae, the secondary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray matter, and other regions. In study 2, we tested the sensitivity and specificity of the signature to pain versus warmth in a new sample. In study 3, we assessed specificity relative to social pain, which activates many of the same brain regions as physical pain. In study 4, we assessed the responsiveness of the measure to the analgesic agent remifentanil. RESULTS In study 1, the neurologic signature showed sensitivity and specificity of 94% or more (95% confidence interval [CI], 89 to 98) in discriminating painful heat from nonpainful warmth, pain anticipation, and pain recall. In study 2, the signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity (95% CI, 84 to 100). In study 3, it discriminated between physical pain and social pain with 85% sensitivity (95% CI, 76 to 94) and 73% specificity (95% CI, 61 to 84) and with 95% sensitivity and specificity in a forced-choice test of which of two conditions was more painful. In study 4, the strength of the signature response was substantially reduced when remifentanil was administered. CONCLUSIONS It is possible to use fMRI to assess pain elicited by noxious heat in healthy persons. Future studies are needed to assess whether the signature predicts clinical pain. (Funded by the National Institute on Drug Abuse and others.).

Interference resolution: insights from a meta-analysis of neuroimaging tasks.

A quantitative meta-analysis was performed on 47 neuroimaging studies involving tasks purported to require the resolution of interference. The tasks included the Stroop, flanker, go/no-go, stimulus-response compatibility, Simon, and stop signal tasks. Peak density-based analyses of these combined tasks reveal that the anterior cingulate cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, posterior parietal cortex, and anterior insula may be important sites for the detection and/or resolution of interference. Individual task analyses reveal differential patterns of activation among the tasks. We propose that the drawing of distinctions among the processing stages at which interference may be resolved may explain regional activation differences. Our analyses suggest that resolution processes acting upon stimulus encoding, response selection, and response execution may recruit different neural regions.