Matthew D. Lieberman

Type I and Type II error concerns in fMRI research: re-balancing the scale

Statistical thresholding (i.e. P-values) in fMRI research has become increasingly conservative over the past decade in an attempt to diminish Type I errors (i.e. false alarms) to a level traditionally allowed in behavioral science research. In this article, we examine the unintended negative consequences of this single-minded devotion to Type I errors: increased Type II errors (i.e. missing true effects), a bias toward studying large rather than small effects, a bias toward observing sensory and motor processes rather than complex cognitive and affective processes and deficient meta-analyses. Power analyses indicate that the reductions in acceptable P-values over time are producing dramatic increases in the Type II error rate. Moreover, the push for a mapwide false discovery rate (FDR) of 0.05 is based on the assumption that this is the FDR in most behavioral research; however, this is an inaccurate assessment of the conventions in actual behavioral research. We report simulations demonstrating that combined intensity and cluster size thresholds such as P < 0.005 with a 10 voxel extent produce a desirable balance between Types I and II error rates. This joint threshold produces high but acceptable Type II error rates and produces a FDR that is comparable to the effective FDR in typical behavioral science articles (while a 20 voxel extent threshold produces an actual FDR of 0.05 with relatively common imaging parameters). We recommend a greater focus on replication and meta-analysis rather than emphasizing single studies as the unit of analysis for establishing scientific truth. From this perspective, Type I errors are self-erasing because they will not replicate, thus allowing for more lenient thresholding to avoid Type II errors.

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.

Intuition: A social cognitive neuroscience approach.

This review proposes that implicit learning processes are the cognitive substrate of social intuition. This hypothesis is supported by (a) the conceptual correspondence between implicit learning and social intuition (nonverbal communication) and (b) a review of relevant neuropsychological (Huntingtons and Parkinsons disease), neuroimaging, neurophysiological, and neuroanatomical data. It is concluded that the caudate and putamen, in the basal ganglia, are central components of both intuition and implicit learning, supporting the proposed relationship. Parallel, but distinct, processes of judgment and action are demonstrated at each of the social, cognitive, and neural levels of analysis. Additionally, explicit attempts to learn a sequence can interfere with implicit learning. The possible relevance of the computations of the basal ganglia to emotional appraisal, automatic evaluation, script processing, and decision making are discussed.

The emergence of social cognitive neuroscience.

Social cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand phenomena in terms of interactions between 3 levels of analysis: the social level, which is concerned with the motivational and social factors that influence behavior and experience; the cognitive level, which is concerned with the information-processing mechanisms that give rise to social-level phenomena; and the neural level, which is concerned with the brain mechanisms that instantiate cognitive-level processes. The social cognitive neuroscience approach entails conducting studies and constructing theories that make reference to all 3 levels and contrasts with traditional social psychological and cognitive neuroscientific research that primarily makes reference to 2 levels. The authors present an introduction to and analysis of the field by reviewing current research and providing guidelines and suggested directions for future work.

The Sunny Side of Fairness Preference for Fairness Activates Reward Circuitry (and Disregarding Unfairness Activates Self-Control Circuitry)

Little is known about the positive emotional impact of fairness or the process of resolving conflict between fairness and financial interests. In past research, fairness has covaried with monetary payoff, such that the mental processes underlying preference for fairness and those underlying preference for greater monetary outcome could not be distinguished. We examined self-reported happiness and neural responses to fair and unfair offers while controlling for monetary payoff. Compared with unfair offers of equal monetary value, fair offers led to higher happiness ratings and activation in several reward regions of the brain. Furthermore, the tendency to accept unfair proposals was associated with increased activity in right ventrolateral prefrontal cortex, a region involved in emotion regulation, and with decreased activity in the anterior insula, which has been implicated in negative affect. This work provides evidence that fairness is hedonically valued and that tolerating unfair treatment for material gain involves a pattern of activation resembling suppression of negative affect.

Serotonin Modulates Behavioral Reactions to Unfairness

Serotonin (5-HT) has long been implicated in social behavior and impulsivity, but the mechanisms through which it modulates self-control remain unclear. We observed the effects of manipulating 5-HT function on behavior in the ultimatum game, where players must decide whether to accept or reject fair or unfair monetary offers from another player. Participants with depleted 5-HT levels rejected a greater proportion of unfair offers, but not fair offers, without showing changes in mood, fairness judgment, basic reward processing, or response inhibition. Our results suggest that 5-HT plays a critical role in regulating emotion during social decision-making.

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.

The neural correlates of placebo effects: a disruption account.

The neurocognitive pathways by which placebo effects operate are poorly understood. Positron emission tomography (PET) imaging was used to assess the brain response of patients with chronic abdominal pain (irritable bowel syndrome; IBS) to induced intestinal discomfort both before and after a 3-week placebo regimen. A daily symptom diary was used to measure symptom improvement. Increases in right ventrolateral prefrontal cortex (RVLPFC) activity from pre- to post-placebo predicted self-reported symptom improvement, and this relationship was mediated by changes in dorsal anterior cingulate (dACC), typically associated with pain unpleasantness. These results are consistent with disruption theory [Lieberman, M.D., 2003. Reflective and reflexive judgment processes: a social cognitive neuroscience approach. In: Forgas, J.P., Williams, K.R., von Hippel, W. (Eds.), Social Judgments: Explicit and Implicit Processes. Cambridge Univ. Press, New York, pp. 44-67], which proposes that activation of prefrontal regions associated with thinking about negative affect can diminish dACC and amygdala reactivity to negative affect stimuli. This is the first study to identify a neural pathway from a region of the brain associated with placebos and affective thought to a region closely linked to the placebo-related outcome of diminished pain unpleasantness.