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1.  Multimodal analysis of cortical chemoarchitecture and macroscale fMRI resting‐state functional connectivity 
Human Brain Mapping  2016;37(9):3103-3113.
Abstract
The cerebral cortex is well known to display a large variation in excitatory and inhibitory chemoarchitecture, but the effect of this variation on global scale functional neural communication and synchronization patterns remains less well understood. Here, we provide evidence of the chemoarchitecture of cortical regions to be associated with large‐scale region‐to‐region resting‐state functional connectivity. We assessed the excitatory versus inhibitory chemoarchitecture of cortical areas as an ExIn ratio between receptor density mappings of excitatory (AMPA, M1) and inhibitory (GABAA, M2) receptors, computed on the basis of data collated from pioneering studies of autoradiography mappings as present in literature of the human (2 datasets) and macaque (1 dataset) cortex. Cortical variation in ExIn ratio significantly correlated with total level of functional connectivity as derived from resting‐state functional connectivity recordings of cortical areas across all three datasets (human I: P = 0.0004; human II: P = 0.0008; macaque: P = 0.0007), suggesting cortical areas with an overall more excitatory character to show higher levels of intrinsic functional connectivity during resting‐state. Our findings are indicative of the microscale chemoarchitecture of cortical regions to be related to resting‐state fMRI connectivity patterns at the global system's level of connectome organization. Hum Brain Mapp 37:3103–3113, 2016. © 2016 Wiley Periodicals, Inc.
doi:10.1002/hbm.23229
PMCID: PMC5111767  PMID: 27207489
fMRI; functional connectivity; chemoarchitecture; receptor; excitatory; inhibitory; connectome; resting‐state fMRI
2.  Methodological Recommendations for a Heartbeat Detection-Based Measure of Interoceptive Sensitivity 
Psychophysiology  2015;52(11):1432-1440.
Heartbeat detection tasks are often used to measure cardiac interoceptive sensitivity: the ability to detect sensations from one’s heart. However, there is little work to guide decisions on the optimum number of trials to use, which should balance reliability and power against task duration and participant burden. Here, 174 participants completed 100 trials of a widely-used heartbeat detection task where participants attempt to detect whether presented tones occurred synchronously or asynchronously with their heartbeats. First, we quantified measurement reliability of the participant’s accuracy derived from differing numbers of trials of the task using a correlation metric; we found that at least 40–60 trials were required to yield sufficient reliability. Next, we quantified power by simulating how the number of trials influenced the ability to detect a correlation between cardiac interoceptive sensitivity and other variables that differ across participants, including a variable measured from our sample (body mass index) as well as simulated variables of varying effect sizes. Using these simulations, we quantified the trade-offs between sample size, effect size, and number of trials in the heartbeat detection task such that a researcher can easily determine any one of these variables at given values of the other two variables. We conclude that using fewer than forty trials is typically insufficient due to poor reliability and low power in estimating an effect size, although the optimal number of trials can differ by study.
doi:10.1111/psyp.12503
PMCID: PMC4821012  PMID: 26265009
heartbeat detection; interoceptive sensitivity; reliability; power calculation; simulation
3.  Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging 
The Journal of Neuroscience  2016;36(37):9659-9668.
Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function.
SIGNIFICANCE STATEMENT Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with youthful memory performance) would exhibit preserved neuroanatomy in key brain networks subserving memory. We found that superagers not only perform similarly to young adults on memory testing, they also do not show the typical patterns of brain atrophy in certain regions. These regions are contained largely within two major intrinsic brain networks: the default mode network, implicated in memory encoding, storage, and retrieval, and the salience network, associated with attention and executive processes involved in encoding and retrieval. Preserved neuroanatomical integrity in these networks is associated with better memory performance among older adults.
doi:10.1523/JNEUROSCI.1492-16.2016
PMCID: PMC5039247  PMID: 27629716
aging; cerebral cortex; default mode network; memory; salience network
4.  Intrinsic connectivity in the human brain does not reveal networks for ‘basic’ emotions 
We tested two competing models for the brain basis of emotion, the basic emotion theory and the conceptual act theory of emotion, using resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). The basic emotion view hypothesizes that anger, sadness, fear, disgust and happiness each arise from a brain network that is innate, anatomically constrained and homologous in other animals. The conceptual act theory of emotion hypothesizes that an instance of emotion is a brain state constructed from the interaction of domain-general, core systems within the brain such as the salience, default mode and frontoparietal control networks. Using peak coordinates derived from a meta-analysis of task-evoked emotion fMRI studies, we generated a set of whole-brain rs-fcMRI ‘discovery’ maps for each emotion category and examined the spatial overlap in their conjunctions. Instead of discovering a specific network for each emotion category, variance in the discovery maps was accounted for by the known domain-general network. Furthermore, the salience network is observed as part of every emotion category. These results indicate that specific networks for each emotion do not exist within the intrinsic architecture of the human brain and instead support the conceptual act theory of emotion.
doi:10.1093/scan/nsv013
PMCID: PMC4560947  PMID: 25680990
emotions; intrinsic functional connectivity networks; basic emotion theory; conceptual act theory of emotion
5.  Establishing the situated features associated with perceived stress 
Acta psychologica  2016;169:119-132.
We propose that the domain general process of categorization contributes to the perception of stress. When a situation contains features associated with stressful experiences, it is categorized as stressful. From the perspective of situated cognition, the features used to categorize experiences as stressful are the features typically true of stressful situations. To test this hypothesis, we asked participants to evaluate the perceived stress of 572 imagined situations, and to also evaluate each situation for how much it possessed 19 features potentially associated with stressful situations and their processing (e.g., self-threat, familiarity, visual imagery, outcome certainty). Following variable reduction through factor analysis, a core set of 8 features associated with stressful situations—expectation violation, self-threat, coping efficacy, bodily experience, arousal, negative valence, positive valence, and perseveration—all loaded on a single Core Stress Features factor. In a multilevel model, this factor and an Imagery factor explained 88% of the variance in judgments of perceived stress, with significant random effects reflecting differences in how individual participants categorized stress. These results support the hypothesis that people categorize situations as stressful to the extent that typical features of stressful situations are present. To our knowledge, this is the first attempt to establish a comprehensive set of features that predicts perceived stress.
doi:10.1016/j.actpsy.2016.05.012
PMCID: PMC4987261  PMID: 27288834
Stress; Perceived stress; Categorization; Stress categorization; Situated cognition; Appraisal
6.  Affective Beliefs Influence the Experience of Eating Meat 
PLoS ONE  2016;11(8):e0160424.
People believe they experience the world objectively, but research continually demonstrates that beliefs influence perception. Emerging research indicates that beliefs influence the experience of eating. In three studies, we test whether beliefs about how animals are raised can influence the experience of eating meat. Samples of meat were paired with descriptions of animals raised on factory farms or raised on humane farms. Importantly, the meat samples in both conditions were identical. However, participants experienced the samples differently: meat paired with factory farm descriptions looked, smelled, and tasted less pleasant. Even basic properties of flavor were influenced: factory farmed samples tasted more salty and greasy. Finally, actual behavior was influenced: participants consumed less when samples were paired with factory farm descriptions. These findings demonstrate that the experience of eating is not determined solely by physical properties of stimuli—beliefs also shape experience.
doi:10.1371/journal.pone.0160424
PMCID: PMC4996498  PMID: 27556643
7.  The amygdala as a hub in brain networks that support social life 
Neuropsychologia  2014;63:235-248.
A growing body of evidence suggests that the amygdala is central to handling the demands of complex social life in primates. In this paper, we synthesize extant anatomical and functional data from rodents, monkeys, and humans to describe the topography of three partially distinct large-scale brain networks anchored in the amygdala that each support unique functions for effectively managing social interactions and maintaining social relationships. These findings provide a powerful componential framework for parsing social behavior into partially distinct neural underpinnings that differ among healthy people and disintegrate or fail to develop in neuropsychiatric populations marked by social impairment, such as autism, antisocial personality disorder, and frontotemporal dementia.
doi:10.1016/j.neuropsychologia.2014.08.013
PMCID: PMC4981504  PMID: 25152530
Amygdala; Networks; Social life; Social brain; Social network
8.  A Shift in Perspective: Decentering through Mindful Attention to Imagined Stressful Events 
Neuropsychologia  2015;75:505-524.
Ruminative thoughts about a stressful event can seem subjectively real, as if the imagined event were happening in the moment. One possibility is that this subjective realism results from simulating the self as engaged in the stressful event (immersion). If so, then the process of decentering—disengaging the self from the event—should reduce the subjective realism associated with immersion, and therefore perceived stressfulness. To assess this account of decentering, we taught non-meditators a strategy for disengaging from imagined events, simply viewing these events as transient mental states (mindful attention). In a subsequent neuroimaging session, participants imagined stressful and non-stressful events, while either immersing themselves or adopting mindful attention. In conjunction analyses, mindful attention down-regulated the processing of stressful events relative to baseline, whereas immersion up-regulated their processing. In direct contrasts between mindful attention and immersion, mindful attention showed greater activity in brain areas associated with perspective shifting and effortful attention, whereas immersion showed greater activity in areas associated with self-processing and visceral states. These results suggest that mindful attention produces decentering by disengaging embodied senses of self from imagined situations so that affect does not develop.
doi:10.1016/j.neuropsychologia.2015.05.030
PMCID: PMC4631025  PMID: 26111487
mental simulation; mindfulness; neuroimaging; self; stress; decentering
9.  Out of Sight but Not Out of Mind: Unseen Affective Faces Influence Evaluations and Social Impressions 
Emotion (Washington, D.C.)  2012;12(6):1210-1221.
Using Continuous Flash Suppression (CFS), we demonstrated in four experiments that affective information extracted from unseen faces influences both affective and personality judgments of neutral faces. In four experiments, participants judged neutral faces as more pleasant or unpleasant (Studies 1 and 2) or as more or less trustworthy, likable, and attractive (Study 3) or as more or less competent or interpersonally warm (Study 4) when paired with unseen smiling or scowling faces compared to when paired with unseen neutral faces. These findings suggest that affective influences are a normal part of everyday experience and provide evidence for the affective foundations consciousness. Affective misattribution arises even when affective changes occur after a neutral stimulus is presented, demonstrating that these affective influences cannot be explained as a simple semantic priming effect. These findings have implications for understanding the constructive nature of experience, as well as the role of affect in social impressions.
doi:10.1037/a0027514
PMCID: PMC4957816  PMID: 22506501
affect; continuous flash suppression; consciousness; person perception
10.  Unseen positive and negative affective information influences social perception in bipolar I disorder and healthy adults 
Journal of affective disorders  2015;192:191-198.
Bipolar disorder is fundamentally a disorder of emotion regulation, and associated with explicit processing biases for socially relevant emotional information in human faces. Less is known, however, about whether implicit processing of this type of emotional information directly influences social perception. We thus investigated group-related differences in the influence of unconscious emotional processing on conscious person perception judgments using a continuous flash suppression task among 22 individuals with remitted bipolar I disorder (BD; AgeM=30.82, AgeSD=7.04; 68.2% female) compared with 22 healthy adults (CTL; AgeM=20.86, AgeSD=9.91; 72.2% female). Across both groups, participants rated neutral faces as more trustworthy, warm, and competent when paired with unseen happy faces as compared to unseen angry and neutral faces; participants rated neutral faces as less trustworthy, warm, and competent when paired with unseen angry as compared to neutral faces. These findings suggest that emotion-related disturbances are not explained by early automatic processing stages, and that activity in the dorsal visual stream underlying implicit emotion processing is intact in bipolar disorder. Implications for understanding the etiology of emotion disturbance in BD are discussed.
doi:10.1016/j.jad.2015.12.037
PMCID: PMC4873165  PMID: 26745436
Bipolar disorder; Affect; Social perception; Implicit emotion; Unconscious processing; Continuous flash suppression
11.  Affective science perspectives on cancer control: Strategically crafting a mutually beneficial research agenda 
Cancer control research involves the conduct of basic and applied behavioral and social sciences to reduce cancer incidence, morbidity, and mortality, and improve quality of life. Given the importance of behavior in cancer control, fundamental research is necessary to identify psychological mechanisms underlying cancer risk, prevention, and management behaviors. Cancer prevention, diagnosis, and treatment are often emotionally-laden. As such, affective science research to elucidate questions related to basic phenomenological nature of emotion, stress, and mood is necessary to understand how cancer control can be hindered or facilitated by emotional experiences. To date, the intersection of basic affective science research and cancer control remains largely unexplored. The goal of this paper is to outline key questions in the cancer control research domain that provide an ecologically valid context for new affective science discoveries. We also provide examples of ways in which basic affective discoveries could inform future cancer prevention and control research. These examples are not meant to be exhaustive or prescriptive, but instead are offered to generate creative thought about the promise of a cancer research context for answering basic affective science questions. Together, these examples provide a compelling argument for fostering collaborations between affective and cancer control scientists.
doi:10.1177/1745691615576755
PMCID: PMC4438787  PMID: 25987511
12.  Directly Acting Triple Drug Anti-HCV Therapy Induces Sustained Virologic Response with a Six Week Regimen: A Proof of Concept Phase 2a Cohort Study 
Lancet  2015;385(9973):1107-1113.
Background
Direct acting anti-HCV drugs have demonstrated a high cure rate and favorable tolerability. The development of shorter courses of therapy may improve affordability and adherence. Sofosbuvir and ledipasvir together with ribavirin have yielded high efficacy when administered for 8, but not for 6 weeks. We hypothesized that addition of a third potent directly acting antiviral to sofosbuvir and ledipasvir would allow for shortened durations of therapy.
Methods
In this single center, open-label cohort, phase 2 atrial, sixty HCV GT-1 treatment naïve patients were sequentially enrolled onto three arms and treated with 12 weeks of sofosbuvir and ledipasvir (an NS5B nucleotide polymerase inhibitor and an NS5A inhibitor, respectively) (n=20); or 6 weeks with sofosbuvir, ledipasvir, and GS-9669 (a non-nucleoside NS5B inhibitor) (n=20) or 6 weeks with sofosbuvir, ledipasvir and GS-9451 (an NS3/4A protease inhibitor) (n=20). Patients and investigators were unmasked to treatment assignment. The primary efficacy analysis was SVR12 (HCV RNA less than the level of quantitation 12 weeks after treatment completion).
Findings
All subjects treated with sofosbuvir and ledipasvir for 12 weeks achieved SVR12 (95%CI: 83–100%). Nineteen of 20 patients (95% CI: 75–100%) treated with sofosbuvir, ledipasvir and GS-9669 achieved SVR12, with 1 patient relapsing 2 weeks after completion of therapy. Nineteen of 20 patients (95% CI: 75–100%) treated with sofosbuvir, ledipasvir, and GS-9451 for 6 weeks achieved SVR12, one patient was lost to follow up after achieving SVR4. There were no discontinuations of treatment due to adverse events.
Interpretation
In this small proof of concept study, two different three drug regimens administered for 6 weeks resulted in high cure rates for HCV infection with excellent tolerability.
Funding
NIAID, National Cancer Institute and Clinical Center Intramural Program. Clinical Trials.gov number NCT01805882. The study was also supported in part by the German Research Foundation (DFG) by the clinical research unit KFO 129 and a Collaborative Research and Development Agreement between NIH and Gilead Sciences.
doi:10.1016/S0140-6736(14)61228-9
PMCID: PMC4427052  PMID: 25591505
13.  Brain network connectivity-behavioral relationships exhibit trait-like properties: evidence from hippocampal connectivity and memory 
Hippocampus  2015;25(12):1591-1598.
Despite a growing number of studies showing relationships between behavior and resting-state functional MRI measures of large-scale brain network connectivity, no study to our knowledge has sought to investigate whether intrinsic connectivity-behavioral relationships are stable over time. In this study, we investigated the stability of such brain-behavior relationships at two timepoints, approximately 1 week apart. We focused on the relationship between the strength of hippocampal connectivity to posterior cingulate cortex and episodic memory performance. Our results showed that this relationship is stable across samples of a different age and reliable over two points in time. These findings provide the first evidence that the relationship between large-scale intrinsic network connectivity and episodic memory performance is a stable characteristic that varies between individuals.
doi:10.1002/hipo.22480
PMCID: PMC4775233  PMID: 26105075
resting-state fMRI; hippocampus; individual differences; reliability; memory
14.  Perceptions of Emotion from Facial Expressions are Not Culturally Universal: Evidence from a Remote Culture 
Emotion (Washington, D.C.)  2014;14(2):251-262.
It is widely believed that certain emotions are universally recognized in facial expressions. Recent evidence indicates that Western perceptions (e.g., scowls as anger) depend on cues to US emotion concepts embedded in experiments. Since such cues are standard feature in methods used in cross-cultural experiments, we hypothesized that evidence of universality depends on this conceptual context. In our study, participants from the US and the Himba ethnic group sorted images of posed facial expressions into piles by emotion type. Without cues to emotion concepts, Himba participants did not show the presumed “universal” pattern, whereas US participants produced a pattern with presumed universal features. With cues to emotion concepts, participants in both cultures produced sorts that were closer to the presumed “universal” pattern, although substantial cultural variation persisted. Our findings indicate that perceptions of emotion are not universal, but depend on cultural and conceptual contexts.
doi:10.1037/a0036052
PMCID: PMC4752367  PMID: 24708506
emotion; perception; facial expression; universality; relativity; culture
15.  Interoceptive predictions in the brain 
Nature reviews. Neuroscience  2015;16(7):419-429.
Intuition suggests that perception follows sensation and therefore bodily feelings originate in the body. However, recent evidence goes against this logic: interoceptive experience may largely reflect limbic predictions about the expected state of the body that are constrained by ascending visceral sensations. In this Opinion article, we introduce the Embodied Predictive Interoception Coding model, which integrates an anatomical model of corticocortical connections with Bayesian active inference principles, to propose that agranular visceromotor cortices contribute to interoception by issuing interoceptive predictions. We then discuss how disruptions in interoceptive predictions could function as a common vulnerability for mental and physical illness.
doi:10.1038/nrn3950
PMCID: PMC4731102  PMID: 26016744
16.  CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core Research Group: 2016 Updated Canadian HIV/Hepatitis C Adult Guidelines for Management and Treatment 
Background. Hepatitis C virus (HCV) coinfection occurs in 20–30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.
doi:10.1155/2016/4385643
PMCID: PMC4947683  PMID: 27471521
17.  If it bleeds, it leads: separating threat from mere negativity 
Most theories of emotion hold that negative stimuli are threatening and aversive. Yet in everyday experiences some negative sights (e.g. car wrecks) attract curiosity, whereas others repel (e.g. a weapon pointed in our face). To examine the diversity in negative stimuli, we employed four classes of visual images (Direct Threat, Indirect Threat, Merely Negative and Neutral) in a set of behavioral and functional magnetic resonance imaging studies. Participants reliably discriminated between the images, evaluating Direct Threat stimuli most quickly, and Merely Negative images most slowly. Threat images evoked greater and earlier blood oxygen level-dependent (BOLD) activations in the amygdala and periaqueductal gray, structures implicated in representing and responding to the motivational salience of stimuli. Conversely, the Merely Negative images evoked larger BOLD signal in the parahippocampal, retrosplenial, and medial prefrontal cortices, regions which have been implicated in contextual association processing. Ventrolateral as well as medial and lateral orbitofrontal cortices were activated by both threatening and Merely Negative images. In conclusion, negative visual stimuli can repel or attract scrutiny depending on their current threat potential, which is assessed by dynamic shifts in large-scale brain network activity.
doi:10.1093/scan/nsu007
PMCID: PMC4994838  PMID: 24493851
affect; emotion; scenes; fMRI; valence; arousal
18.  Variety in emotional life: within-category typicality of emotional experiences is associated with neural activity in large-scale brain networks 
The tremendous variability within categories of human emotional experience receives little empirical attention. We hypothesized that atypical instances of emotion categories (e.g. pleasant fear of thrill-seeking) would be processed less efficiently than typical instances of emotion categories (e.g. unpleasant fear of violent threat) in large-scale brain networks. During a novel fMRI paradigm, participants immersed themselves in scenarios designed to induce atypical and typical experiences of fear, sadness or happiness (scenario immersion), and then focused on and rated the pleasant or unpleasant feeling that emerged (valence focus) in most trials. As predicted, reliably greater activity in the ‘default mode’ network (including medial prefrontal cortex and posterior cingulate) was observed for atypical (vs typical) emotional experiences during scenario immersion, suggesting atypical instances require greater conceptual processing to situate the socio-emotional experience. During valence focus, reliably greater activity was observed for atypical (vs typical) emotional experiences in the ‘salience’ network (including anterior insula and anterior cingulate), suggesting atypical instances place greater demands on integrating shifting body signals with the sensory and social context. Consistent with emerging psychological construction approaches to emotion, these findings demonstrate that is it important to study the variability within common categories of emotional experience.
doi:10.1093/scan/nsu037
PMCID: PMC4994840  PMID: 24563528
emotion; affective neuroscience; typicality
19.  Involvement of Sensory Regions in Affective Experience: A Meta-Analysis 
Frontiers in Psychology  2015;6:1860.
A growing body of work suggests that sensory processes may also contribute to affective experience. In this study, we performed a meta-analysis of affective experiences driven through visual, auditory, olfactory, gustatory, and somatosensory stimulus modalities including study contrasts that compared affective stimuli to matched neutral control stimuli. We found, first, that limbic and paralimbic regions, including the amygdala, anterior insula, pre-supplementary motor area, and portions of orbitofrontal cortex were consistently engaged across two or more modalities. Second, early sensory input regions in occipital, temporal, piriform, mid-insular, and primary sensory cortex were frequently engaged during affective experiences driven by visual, auditory, olfactory, gustatory, and somatosensory inputs. A classification analysis demonstrated that the pattern of neural activity across a contrast map diagnosed the stimulus modality driving the affective experience. These findings suggest that affective experiences are constructed from activity that is distributed across limbic and paralimbic brain regions and also activity in sensory cortical regions.
doi:10.3389/fpsyg.2015.01860
PMCID: PMC4678183  PMID: 26696928
emotion; fMRI; meta-analysis; perception; affect
20.  Visual Predictions in the Orbitofrontal Cortex Rely on Associative Content 
Cerebral Cortex (New York, NY)  2013;24(11):2899-2907.
Predicting upcoming events from incomplete information is an essential brain function. The orbitofrontal cortex (OFC) plays a critical role in this process by facilitating recognition of sensory inputs via predictive feedback to sensory cortices. In the visual domain, the OFC is engaged by low spatial frequency (LSF) and magnocellular-biased inputs, but beyond this, we know little about the information content required to activate it. Is the OFC automatically engaged to analyze any LSF information for meaning? Or is it engaged only when LSF information matches preexisting memory associations? We tested these hypotheses and show that only LSF information that could be linked to memory associations engages the OFC. Specifically, LSF stimuli activated the OFC in 2 distinct medial and lateral regions only if they resembled known visual objects. More identifiable objects increased activity in the medial OFC, known for its function in affective responses. Furthermore, these objects also increased the connectivity of the lateral OFC with the ventral visual cortex, a crucial region for object identification. At the interface between sensory, memory, and affective processing, the OFC thus appears to be attuned to the associative content of visual information and to play a central role in visuo-affective prediction.
doi:10.1093/cercor/bht146
PMCID: PMC4193460  PMID: 23771980
fMRI; perception; top-down
21.  Amygdala Task-Evoked Activity and Task-Free Connectivity Independently Contribute to Feelings of Arousal 
Human brain mapping  2014;35(10):5316-5327.
Individual differences in the intensity of feelings of arousal while viewing emotional pictures have been associated with the magnitude of task-evoked blood-oxygen dependent (BOLD) response in the amygdala. Recently, we reported that individual differences in feelings of arousal are associated with task-free (resting state) connectivity within the salience network. There has not yet been an investigation of whether these two types of functional magnetic resonance imaging (MRI) measures are redundant or independent in their relationships to behavior. Here we tested the hypothesis that a combination of task-evoked amygdala activation and task-free amygdala connectivity within the salience network relate to individual differences in feelings of arousal while viewing of negatively potent images. In 25 young adults, results revealed that greater task-evoked amygdala activation and stronger task-free amygdala connectivity within the salience network each contributed independently to feelings of arousal, predicting a total of 45% of its variance. Individuals who had both increased task-evoked amygdala activation and stronger task-free amygdala connectivity within the salience network had the most heightened levels of arousal. Task-evoked amygdala activation and task-free amygdala connectivity within the salience network were not related to each other, suggesting that resting-state and task-evoked dynamic brain imaging measures may provide independent and complementary information about affective experience, and likely other kinds of behaviors as well.
doi:10.1002/hbm.22552
PMCID: PMC4335688  PMID: 24862171
amygdala; task-evoked activation; resting-state connectivity; individual differences; feelings of arousal
22.  Gender differences in oxytocin-associated disruption of decision bias during emotion perception 
Psychiatry research  2014;219(1):198-203.
Oxytocin is associated with differences in the perception of and response to socially mediated information, such as facial expressions. Across studies, however, oxytocin’s effect on emotion perception has been inconsistent. Outside the laboratory, emotion perception involves interpretation of perceptual uncertainty and assessment of behavioral risk. An account of these factors is largely missing from studies of oxytocin’s effect on emotion perception and might explain inconsistent results across studies. Of relevance, studies of oxytocin’s effect on learning and decision-making indicate that oxytocin attenuates risk aversion. We used the probability of encountering angry faces and the cost of misidentifying them as not angry to create a risky environment wherein bias to categorize faces as angry would maximize point earnings. Consistent with an underestimation of the factors creating risk (i.e., encounter rate and cost), men given oxytocin exhibited a worse (i.e., less liberal) response bias than men given placebo. Oxytocin did not influence women’s performance. These results suggest that oxytocin may impair men’s ability to adapt to changes in risk and uncertainty when introduced to novel or changing social environments. Because oxytocin also influences behavior in non-social realms, oxytocin pharmacotherapy could have unintended consequences (i.e., risk-prone decision-making) while nonetheless normalizing pathological social interaction.
doi:10.1016/j.psychres.2014.04.031
PMCID: PMC4086323  PMID: 24814142
Signal detection theory; Face perception; Risk sensitivity; Behavioral economics
23.  AFFECT AND THE FRAMING EFFECT WITHIN INDIVIDUALS OVER TIME: RISK TAKING IN A DYNAMIC INVESTMENT SIMULATION 
We examined the role of affect (pleasant or unpleasant feelings) and decision frames (gains or losses) in risk taking in a 20-day stock investment simulation in which 101 participants rated their current feelings while making investment decisions. As predicted, affect attenuated the relationships between decision frames and risk taking. After experiencing losses, individuals made more risky choices, in keeping with the framing effect. However, this tendency decreased and/or disappeared when loss was simultaneously experienced with either pleasant or unpleasant feelings. Similarly, individuals’ tendency to avoid risk after experiencing gains disappeared or even reversed when they simultaneously experienced pleasant feelings.
doi:10.5465/AMJ.2010.49389383
PMCID: PMC4580376  PMID: 26412860
24.  Sex differences in the persistence of the amygdala response to negative material 
Previous studies have indicated that men and women have different amygdala responses to novel (vs familiar) and valenced (positive vs negative) material. It is not known, however, whether these affective sex differences are related. In this study, we tested whether women have more persistent amygdala responses to familiar, negative material than men do. During fMRI, male and female participants viewed evocative images that varied in novelty and valence. Women and men showed equivalent responses to novel negative material, but women showed a sustained amygdala response to familiar negative material relative to men, indicating that women’s amygdala responses were more persistent over multiple repetitions of negative material. Individuals with more persistent amygdala responses also reported greater levels of negative effect. These findings have implications for sex differences in the incidence of affective disorders.
doi:10.1093/scan/nst127
PMCID: PMC4158377  PMID: 24036962
amygdala; sex; habituation
25.  “UTILIZING” SIGNAL DETECTION THEORY 
Psychological science  2014;25(9):1663-1673.
What do inferring what a person is thinking or feeling, deciding to report a symptom to your doctor, judging a defendant’s guilt, and navigating a dimly lit room have in common? They involve perceptual uncertainty (e.g., a scowling face might indicate anger or concentration, which engender different appropriate responses), and behavioral risk (e.g., a cost to making the wrong response). Signal detection theory describes these types of decisions. In this tutorial we show how, by incorporating the economic concept of utility, signal detection theory serves as a model of optimal decision making, beyond its common use as an analytic method. This utility approach to signal detection theory highlights potentially enigmatic influences of perceptual uncertainty on measures of decision-making performance (accuracy and optimality) and on behavior (a functional relationship between bias and sensitivity). A “utilized” signal detection theory offers the possibility of expanding the phenomena that can be understood within a decision-making framework.
doi:10.1177/0956797614541991
PMCID: PMC4304641  PMID: 25097061
Signal detection theory; utility; perception; decision making

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