Naomi I. Eisenberger

Putting Feelings Into Words Affect Labeling Disrupts Amygdala Activity in Response to Affective Stimuli

Putting feelings into words (affect labeling) has long been thought to help manage negative emotional experiences; however, the mechanisms by which affect labeling produces this benefit remain largely unknown. Recent neuroimaging studies suggest a possible neurocognitive pathway for this process, but methodological limitations of previous studies have prevented strong inferences from being drawn. A functional magnetic resonance imaging study of affect labeling was conducted to remedy these limitations. The results indicated that affect labeling, relative to other forms of encoding, diminished the response of the amygdala and other limbic regions to negative emotional images. Additionally, affect labeling produced increased activity in a single brain region, right ventrolateral prefrontal cortex (RVLPFC). Finally, RVLPFC and amygdala activity during affect labeling were inversely correlated, a relationship that was mediated by activity in medial prefrontal cortex (MPFC). These results suggest that affect labeling may diminish emotional reactivity along a pathway from RVLPFC to MPFC to the amygdala.

Neural correlates of dispositional mindfulness during affect labeling.

Objective: Mindfulness is a process whereby one is aware and receptive to present moment experiences. Although mindfulness-enhancing interventions reduce pathological mental and physical health symptoms across a wide variety of conditions and diseases, the mechanisms underlying these effects remain unknown. Converging evidence from the mindfulness and neuroscience literature suggests that labeling affect may be one mechanism for these effects. Methods: Participants (n = 27) indicated trait levels of mindfulness and then completed an affect labeling task while undergoing functional magnetic resonance imaging. The labeling task consisted of matching facial expressions to appropriate affect words (affect labeling) or to gender-appropriate names (gender labeling control task). Results: After controlling for multiple individual difference measures, dispositional mindfulness was associated with greater widespread prefrontal cortical activation, and reduced bilateral amygdala activity during affect labeling, compared with the gender labeling control task. Further, strong negative associations were found between areas of prefrontal cortex and right amygdala responses in participants high in mindfulness but not in participants low in mindfulness. Conclusions: The present findings with a dispositional measure of mindfulness suggest one potential neurocognitive mechanism for understanding how mindfulness meditation interventions reduce negative affect and improve health outcomes, showing that mindfulness is associated with enhanced prefrontal cortical regulation of affect through labeling of negative affective stimuli. fMRI = functional magnetic resonance imaging; PFC = prefrontal cortex; VLPFC = ventrolateral prefrontal cortex; VMPFC = ventromedial prefrontal cortex; MPFC = medial prefrontal cortex; DLPFC = dorsolateral prefrontal cortex.

Early Family Environment, Current Adversity, the Serotonin Transporter Promoter Polymorphism, and Depressive Symptomatology

BACKGROUND Mixed evidence has suggested that homozygous carriers of the short allele (s/s) of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) may be at increased risk for depression, if they have also been exposed to early or current adversity/stress. We address this debate by examining the relation of a stressful early family environment, recent adversity/stress, and the 5-HTTLPR to depressive symptomatology in a normal sample. METHODS A nonclinical sample of 118 young adult men and women completed assessments of early family environment, recent stressful events, psychosocial resources, and psychological distress, including depressive symptomatology. The 5-HTTLPR was genotyped using a standard protocol with DNA extracted from oral fluid. RESULTS A stressful early family environment was significantly related to depressive symptomatology. In addition, gene-by-environment (GxE) interactions were observed between the 5-HTTLPR and both early family environment and current adversity/stress. Individuals homozygous for the short allele had greater depressive symptomatology if they had experienced early or recent adversity but significantly less depressive symptomatology if they reported a supportive early environment or recent positive experiences, compared with participants with the s/l or l/l genotype. CONCLUSIONS Early or current environment, in conjunction with the serotonin transporter polymorphism, predicts depressive symptomatology.

Neural pathways link social support to attenuated neuroendocrine stress responses

It is well established that a lack of social support constitutes a major risk factor for morbidity and mortality, comparable to risk factors such as smoking, obesity, and high blood pressure. Although it has been hypothesized that social support may benefit health by reducing physiological reactivity to stressors, the mechanisms underlying this process remain unclear. Moreover, to date, no studies have investigated the neurocognitive mechanisms that translate experiences of social support into the health outcomes that follow. To investigate these processes, thirty participants completed three tasks in which daily social support, neurocognitive reactivity to a social stressor, and neuroendocrine responses to a social stressor were assessed. Individuals who interacted regularly with supportive individuals across a 10-day period showed diminished cortisol reactivity to a social stressor. Moreover, greater social support and diminished cortisol responses were associated with diminished activity in the dorsal anterior cingulate cortex (dACC) and Brodmanns area (BA) 8, regions previously associated with the distress of social separation. Lastly, individual differences in dACC and BA 8 reactivity mediated the relationship between high daily social support and low cortisol reactivity, such that supported individuals showed reduced neurocognitive reactivity to social stressors, which in turn was associated with reduced neuroendocrine stress responses. This study is the first to investigate the neural underpinnings of the social support-health relationship and provides evidence that social support may ultimately benefit health by diminishing neural and physiological reactivity to social stressors.

An fMRI investigation of race-related amygdala activity in African-American and Caucasian-American individuals

Functional magnetic resonance imaging (fMRI) was used to examine the nature of amygdala sensitivity to race. Both African-American and Caucasian-American individuals showed greater amygdala activity to African-American targets than to Caucasian-American targets, suggesting that race-related amygdala activity may result from cultural learning rather than from the novelty of other races. Additionally, verbal encoding of African-American targets produced significantly less amygdala activity than perceptual encoding of African-American targets.

Acetaminophen Reduces Social Pain Behavioral and Neural Evidence

Pain, whether caused by physical injury or social rejection, is an inevitable part of life. These two types of pain—physical and social—may rely on some of the same behavioral and neural mechanisms that register pain-related affect. To the extent that these pain processes overlap, acetaminophen, a physical pain suppressant that acts through central (rather than peripheral) neural mechanisms, may also reduce behavioral and neural responses to social rejection. In two experiments, participants took acetaminophen or placebo daily for 3 weeks. Doses of acetaminophen reduced reports of social pain on a daily basis (Experiment 1). We used functional magnetic resonance imaging to measure participants’ brain activity (Experiment 2), and found that acetaminophen reduced neural responses to social rejection in brain regions previously associated with distress caused by social pain and the affective component of physical pain (dorsal anterior cingulate cortex, anterior insula). Thus, acetaminophen reduces behavioral and neural responses associated with the pain of social rejection, demonstrating substantial overlap between social and physical pain.

Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.

BACKGROUND Although inflammatory activity is known to play a role in depression, no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia, a key diagnostic symptom of depression. To investigate this, we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely, reduced ventral striatum (VS) activity to reward cues. We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood. METHODS Participants (n = 39) were randomly assigned to receive either placebo or low-dose endotoxin, which increases proinflammatory cytokine levels in a safe manner. Cytokine levels were repeatedly assessed through hourly blood draws; self-reported and observer-rated depressed mood were assessed regularly as well. Two hours after drug administration, neural activity was recorded as participants completed a task in which they anticipated monetary rewards. RESULTS Results demonstrated that subjects exposed to endotoxin, compared with placebo, showed greater increases in self-reported and observer-rated depressed mood over time, as well as significant reductions in VS activity to monetary reward cues. Moreover, the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward. CONCLUSIONS The data reported here show, for the first time, that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood. As such, these findings have implications for understanding risk of depression in persons with underlying inflammation.

Neural sensitivity to social rejection is associated with inflammatory responses to social stress

Although stress-induced increases in inflammation have been implicated in several major disorders, including cardiovascular disease and depression, the neurocognitive pathways that underlie inflammatory responses to stress remain largely unknown. To examine these processes, we recruited 124 healthy young adult participants to complete a laboratory-based social stressor while markers of inflammatory activity were obtained from oral fluids. A subset of participants (n = 31) later completed an fMRI session in which their neural responses to social rejection were assessed. As predicted, exposure to the laboratory-based social stressor was associated with significant increases in two markers of inflammatory activity, namely a soluble receptor for tumor necrosis factor-α (sTNFαRII) and interleukin-6 (IL-6). In the neuroimaging subsample, greater increases in sTNFαRII (but not IL-6) were associated with greater activity in the dorsal anterior cingulate cortex and anterior insula, brain regions that have previously been associated with processing rejection-related distress and negative affect. These data thus elucidate a neurocognitive pathway that may be involved in potentiated inflammatory responses to acute social stress. As such, they have implications for understanding how social stressors may promote susceptibility to diseases with an inflammatory component.

Attachment figures activate a safety signal-related neural region and reduce pain experience

Although it has long been hypothesized that attachment figures provide individuals with a sense of safety and security, the neural mechanisms underlying attachment-induced safety have not been explored. Here, we investigated whether an attachment figure acts as a safety signal by exploring whether viewing an attachment figure during a threatening experience (physical pain) led to increased activity in a neural region associated with safety signaling, the ventromedial prefrontal cortex (VMPFC), and corresponding reductions in pain. Female participants in long-term romantic relationships were scanned as they received painful stimuli while viewing pictures of their partner and control images (stranger, object). Consistent with the idea that the attachment figure may signal safety, results revealed that viewing partner pictures while receiving painful stimulation led to reductions in self-reported pain ratings, reductions in pain-related neural activity (dorsal anterior cingulate cortex, anterior insula), and increased activity in the VMPFC. Moreover, greater VMPFC activity in response to partner pictures was associated with longer relationship lengths and greater perceived partner support, further highlighting a role for the VMPFC in responding to the safety value of the partner. Last, greater VMPFC activity while viewing partner pictures was associated with reduced pain ratings and reduced pain-related neural activity. An implication of these findings is that, in the same way that stimuli that historically have threatened survival (e.g., snakes, spiders) are considered to be prepared fear stimuli, attachment figures, who have historically benefited survival, may serve as prepared safety stimuli, reducing threat- or distress-related responding in their presence.

Evidence for deficient modulation of amygdala response by prefrontal cortex in bipolar mania.

Several studies have implicated the involvement of two major components of emotion regulatory networks, the ventrolateral prefrontal cortex (VLPFC) and amygdala, in the pathophysiology of bipolar disorder. In healthy subjects, the VLPFC has been shown to negatively modulate amygdala response when subjects cognitively evaluate an emotional face by identifying and labeling the emotion it expresses. The current study used such a paradigm to assess whether the strength of this modulation was altered in bipolar subjects when manic. During functional magnetic resonance imaging (fMRI), nine manic subjects with bipolar I disorder and nine healthy subjects either named the emotion shown in a face by identifying one of two words that correctly expressed the emotion (emotion labeling task) or matched the emotion shown in a face to one of two other faces (emotion perception task). The degree to which the VLPFC regulated amygdala response during these tasks was assessed using a psychophysiological interaction (PPI) analysis. Compared with healthy subjects, manic patients had a significantly reduced VLPFC regulation of amygdala response during the emotion labeling task. These findings, taken in context with previous fMRI studies of bipolar mania, suggest that reductions in inhibitory frontal activity in these patients may lead to an increased reactivity of the amygdala.