Gadi Gilam

All Publications

• What Is the Relationship between Pain and Emotion? Bridging Constructs and Communities. Neuron Gilam, G., Gross, J. J., Wager, T. D., Keefe, F. J., Mackey, S. C. 2020

  Abstract

  Although pain is defined as a sensory and emotional experience, it is traditionally researched and clinically treated separately from emotion. Conceptual and mechanistic relationships between these constructs highlight the need for better understanding of their bi-directional influences and the value of bridging the pain and emotion research and clinical communities.

  View details for DOI 10.1016/j.neuron.2020.05.024

  View details for PubMedID 32562660

• Resting State Functional Connectivity Machine Learning Classification of Chronic Back Pain Weber, K. A., Law, C. S., Asher, Y. K., Martucci, K. T., Gilam, G., Lewis, B., Narayan, S., Hastie, T., Wager, T. D., Mackey, S. WILEY. 2019: S266

  View details for Web of Science ID 000488891800418

• Negative Affect-Related Factors Have the Strongest Association with Prescription Opioid Misuse in a Cross-Sectional Cohort of Patients with Chronic Pain. Pain medicine (Malden, Mass.) Gilam, G., Sturgeon, J. A., You, D. S., Wasan, A. D., Darnall, B. D., Mackey, S. C. 2019

  Abstract

  Increased opioid prescription to relieve pain among patients with chronic pain is associated with increased risk for misuse, potentially leading to substance use disorders and overdose death. We aimed to characterize the relative importance and identify the most significant of several potential risk factors for the severity of self-reported prescribed opioid misuse behaviors.A sample of 1,193 patients (mean age ± SD = 50.72 ± 14.97 years, 64.04% female) with various chronic pain conditions completed a multidimensional registry assessing four pain severity measures and 14 physical, mental, and social health status factors using the National Institutes of Health's Patient-Reported Outcomes Measurement Information System (PROMIS). A validated PROMIS measure of medication misuse was completed by 692 patients who endorsed currently taking opioid medication. Patients taking opioid medications were compared across all measures with those who do not take opioid medications. Subsequently, a data-driven regression analysis was used to determine which measures best explained variability in severity of misuse. We hypothesized that negative affect-related factors, namely anxiety, anger, and/or depression, would be key predictors of misuse severity due to their crucial role in chronic pain and substance use disorders.Patients taking opioid medications had significantly greater impairment across most measures. Above and beyond demographic variables, the only and most significant predictors of prescribed opioid misuse severity were as follows: anxiety (β = 0.15, P = 0.01), anger (β = 0.13, P = 0.02), Pain Intensity-worst (β = 0.09, P = 0.02), and depression (β = 0.13, P = 0.04).Findings suggest that anxiety, anger, and depression are key factors associated with prescribed opioid misuse tendencies in patients with chronic pain and that they are potential targets for therapeutic intervention.

  View details for DOI 10.1093/pm/pnz249

  View details for PubMedID 31617916

• The feeling of anger: from brain networks to linguistic expressions. Neuroscience and biobehavioral reviews Alia-Klein, N., Gan, G., Gilam, G., Bezek, J., Bruno, A., Denson, T. F., Hendler, T., Lowe, L., Mariotti, V., Muscatello, M. R., Palumbo, S., Pellegrini, S., Pietrini, P., Rizzo, A., Verona, E. 2019

  Abstract

  This review of the neuroscience of anger is part of The Human Affectome Project, where we attempt to map anger and its components (i.e., physiological, cognitive, experiential) to the neuroscience literature (i.e., genetic markers, functional imaging of human brain networks) and to linguistic expressions used to describe anger feelings. Given the ubiquity of anger in both its normative and chronic states, specific language is used in humans to express states of anger. Following a review of the neuroscience literature, we explore the language that is used to convey angry feelings, as well as metaphors reflecting inner states of anger experience. We then discuss whether these linguistic expressions can be mapped on to the neural circuits during anger experience and to distinct components of anger. We also identify relationships between anger components, brain networks, and other affective research relevant to motivational states of dominance and basic needs for safety.

  View details for DOI 10.1016/j.neubiorev.2019.12.002

  View details for PubMedID 31809773

• Evaluation of Candidate Items for Severe PTSD Screening for Patients with Chronic Pain: Pilot Data Analysis with IRT Approach. Pain practice : the official journal of World Institute of Pain You, D. S., Ziadni, M. S., Gilam, G., Darnall, B. D., Mackey, S. C. 2019

  Abstract

  Post-traumatic Stress Disorder (PTSD) commonly co-occurs with chronic pain. Although PTSD symptoms are associated with negative health outcomes in patients with chronic pain, PTSD is typically under-detected and under-treated in outpatient pain settings. There is a need for rapid, brief screening tools to identify those at greatest risk for severe PTSD symptoms. To achieve that goal, our aim was to use item response theory (IRT) to identify the most informative PTSD symptoms characterizing severe PTSD in patients with chronic pain.Fifty-six patients (71% female, 61% White) with mixed etiology chronic pain completed the PTSD Checklist Civilian Version (PCL-C) as part of their appointment with a pain psychologist at a tertiary outpatient pain clinic. We used an IRT approach to evaluate each item's discriminant (a) and severity (b) parameters.Findings revealed that 'feeling upset at reminders' (a = 3.67, b = 2.44) and 'avoid thinking or talking about it' (a = 3.61, b = 2.17) as being highly discriminant for severe PTSD.We identified two candidate items for a brief PTSD screener as they were associated with severe PTSD symptoms. These two items may provide clinical utility in outpatient pain treatment settings to identify those suffering from severe PTSD enabling physicians to refer them to trauma-specific evaluation or therapy. Future research is needed to further validate and confirm these candidate PTSD items in a larger clinic sample.

  View details for DOI 10.1111/papr.12848

  View details for PubMedID 31646748

• Attenuating anger and aggression with neuromodulation of the vmPFC: A simultaneous tDCS-fMRI study. Cortex; a journal devoted to the study of the nervous system and behavior Gilam, G., Abend, R., Gurevitch, G., Erdman, A., Baker, H., Ben-Zion, Z., Hendler, T. 2018; 109: 156–70

  Abstract

  Angry outbursts during interpersonal provocations may lead to violence and prevails in numerous pathological conditions. In the anger-infused Ultimatum Game (aiUG), unfair monetary offers accompanied by written provocations induce anger. Rejection of such offers relates to aggression, whereas acceptance to anger regulation. We previously demonstrated the involvement of the ventro-medial prefrontal cortex (vmPFC) in accepting unfair offers and attenuating anger during an aiUG, suggestive of its role in anger regulation. Here, we aimed to enhance anger regulation by facilitating vmPFC activity during anger induction, using anodal transcranial direct current stimulation (tDCS) and simultaneously with functional Magnetic Resonance Imaging to validate modulation of vmPFC activity. In a cross-over, sham-controlled, double-blind study, participants (N=25) were each scanned twice, counterbalancing sham and active tDCS applied during administration of the aiUG. Outcome measures included the effect of active versus sham stimulation on vmPFC activity, unfair offers' acceptance rates, self-reported anger, and aggressive behavior in a subsequent reactive aggression paradigm. Results indicate that active stimulation led to increased vmPFC activity during the processing of unfair offers, increased acceptance rates of these offers, and mitigated the increase in self-reported anger following the aiUG. We also noted a decrease in subsequent aggressive behavior following active stimulation, but only when active stimulation was conducted in the first experimental session. Finally, an exploratory finding indicated that participants with a stronger habitual tendency to use suppression as an emotion regulation strategy, reported less anger following the aiUG in the active compared to sham stimulation conditions. Findings support a potential causal link between vmPFC functionality and the experience and expression of anger, supporting vmPFC's role in anger regulation, and providing a promising avenue for reducing angry and aggressive outbursts during interpersonal provocations in various psychiatric and medical conditions.

  View details for PubMedID 30343211

• Anger Modulates Influence Hierarchies Within and Between Emotional Reactivity and Regulation Networks FRONTIERS IN BEHAVIORAL NEUROSCIENCE Jacob, Y., Gilam, G., Lin, T., Raz, G., Hendler, T. 2018; 12: 60

  Abstract

  Emotion regulation is hypothesized to be mediated by the interactions between emotional reactivity and regulation networks during the dynamic unfolding of the emotional episode. Yet, it remains unclear how to delineate the effective relationships between these networks. In this study, we examined the aforementioned networks' information flow hierarchy during viewing of an anger provoking movie excerpt. Anger regulation is particularly essential for averting individuals from aggression and violence, thus improving prosocial behavior. Using subjective ratings of anger intensity we differentiated between low and high anger periods of the film. We then applied the Dependency Network Analysis (DEPNA), a newly developed graph theory method to quantify networks' node importance during the two anger periods. The DEPNA analysis revealed that the impact of the ventromedial prefrontal cortex (vmPFC) was higher in the high anger condition, particularly within the regulation network and on the connections between the reactivity and regulation networks. We further showed that higher levels of vmPFC impact on the regulation network were associated with lower subjective anger intensity during the high-anger cinematic period, and lower trait anger levels. Supporting and replicating previous findings, these results emphasize the previously acknowledged central role of vmPFC in modulating negative affect. We further show that the impact of the vmPFC relies on its correlational influence on the connectivity between reactivity and regulation networks. More importantly, the hierarchy network analysis revealed a link between connectivity patterns of the vmPFC and individual differences in anger reactivity and trait, suggesting its potential therapeutic role.

  View details for PubMedID 29681803

• The anger-infused Ultimatum Game: A reliable and valid paradigm to induce and assess anger. Emotion (Washington, D.C.) Gilam, G., Abend, R., Shani, H., Ben-Zion, Z., Hendler, T. 2018

  Abstract

  The Ultimatum Game (UG) is a canonical social decision-making task whereby a proposer divides a sum of money between himself and a responder who accepts or rejects the offer. Studies consistently demonstrate that unfair offers induce anger, and that rejecting such offers relates to aggression. Nevertheless, the UG is limited in interpersonal provocations common to real-life experiences of anger. Moreover, the psychometric properties of the UG as an anger-induction paradigm have yet to be evaluated. Here, to induce a more intense and genuine anger experience, we implemented a modified UG whereby short written provocations congruent with unfairness levels accompanied each offer. We aimed to test whether this anger-infused UG led to more anger and aggressive responses relative to the standard UG and to establish the reliability and validity of both versions. Participants performed either the anger-infused UG or a standard version, repeated twice, a week apart. They also performed the Taylor Aggression Paradigm, a reactive aggression paradigm, and completed emotion ratings and a trait anger inventory. Results indicate similar decreases in acceptance rates with increase in offer unfairness, and increases in reported anger, across both UG versions. Both versions demonstrated strong test-retest reliability. However, the anger-infused UG led to significantly stronger relations with reactive aggression and trait anger compared to the standard UG, providing evidence for better validity. The development of the anger-infused UG as a reliable and valid paradigm is pivotal for the induction and assessment of interpersonal anger and its aggressive expression in basic and clinical research settings. (PsycINFO Database Record

  View details for DOI 10.1037/emo0000435

  View details for PubMedID 29565609

• Tracing the Neural Carryover Effects of Interpersonal Anger on Resting-State fMRI in Men and Their Relation to Traumatic Stress Symptoms in a Subsample of Soldiers FRONTIERS IN BEHAVIORAL NEUROSCIENCE Gilam, G., Maron-Katz, A., Kliper, E., Lin, T., Fruchter, E., Shamir, R., Hendler, T. 2017; 11: 252

  Abstract

  Uncontrolled anger may lead to aggression and is common in various clinical conditions, including post traumatic stress disorder. Emotion regulation strategies may vary with some more adaptive and efficient than others in reducing angry feelings. However, such feelings tend to linger after anger provocation, extending the challenge of coping with anger beyond provocation. Task-independent resting-state (rs) fMRI may be a particularly useful paradigm to reveal neural processes of spontaneous recovery from a preceding negative emotional experience. We aimed to trace the carryover effects of anger on endogenous neural dynamics by applying a data-driven examination of changes in functional connectivity (FC) during rs-fMRI between before and after an interpersonal anger induction (N = 44 men). Anger was induced based on unfair monetary offers in a previously validated decision-making task. We calculated a common measure of global FC (gFC) which captures the level of FC between each region and all other regions in the brain, and examined which brain regions manifested changes in this measure following anger. We next examined the changes in all functional connections of each individuated brain region with all other brain regions to reveal which connections underlie the differences found in the gFC analysis of the previous step. We subsequently examined the relation of the identified neural modulations in the aftermath of anger with state- and trait- like measures associated with anger, including brain structure, and in a subsample of designated infantry soldiers (N = 21), with levels of traumatic stress symptoms (TSS) measured 1 year later following combat-training. The analysis pipeline revealed an increase in right amygdala gFC in the aftermath of anger and specifically with the right inferior frontal gyrus (IFG).We found that the increase in FC between the right amygdala and right IFG following anger was positively associated with smaller right IFG volume, higher trait-anger level and among soldiers with more TSS. Moreover, higher levels of right amygdala gFC at baseline predicted less reported anger during the subsequent anger provocation. The results suggest that increased amygdala-IFG connectivity following anger is associated with maladaptive recovery, and relates to long-term development of stress symptomatology in a subsample of soldiers.

  View details for DOI 10.3389/fnbeh.2017.00252

  View details for Web of Science ID 000418353100001

  View details for PubMedID 29326568

  View details for PubMedCentralID PMC5742339

• Neural indicators of interpersonal anger as cause and consequence of combat training stress symptoms. Psychological medicine Gilam, G., Lin, T., FRUCHTER, E., Hendler, T. 2017; 47 (9): 1561-1572

  Abstract

  Angry outbursts are an important feature of various stress-related disorders, and commonly lead to aggression towards other people. Findings regarding interpersonal anger have linked the ventromedial prefrontal cortex (vmPFC) to anger regulation and the locus coeruleus (LC) to aggression. Both regions were previously associated with traumatic and chronic stress symptoms, yet it is unclear if their functionality represents a consequence of, or possibly also a cause for, stress symptoms. Here we investigated the relationship between the neural trajectory of these indicators of anger and the development and manifestation of stress symptoms.A total of 46 males (29 soldiers, 17 civilians) participated in a prospective functional magnetic resonance imaging experiment in which they played a modified interpersonal anger-provoking Ultimatum Game (UG) at two-points. Soldiers were tested at the beginning and end of combat training, while civilians were tested at the beginning and end of civil service. We assumed that combat training would induce chronic stress and result in increased stress symptoms.Soldiers showed an increase in stress symptoms following combat training while civilians showed no such change following civil service. All participants were angered by the modified UG irrespective of time point. Higher post-combat training stress symptoms were associated with lower pre-combat training vmPFC activation and with higher activation increase in the LC between pre- and post-combat training.Results suggest that during anger-provoking social interactions, flawed vmPFC functionality may serve as a causal risk factor for the development of stress symptoms, and heightened reactivity of the LC possibly reflects a consequence of stress-inducing combat training. These findings provide potential neural targets for therapeutic intervention and inoculation for stress-related psychopathological manifestations of anger.

  View details for DOI 10.1017/S0033291716003354

  View details for PubMedID 28052779

• The Human Coparental Bond Implicates Distinct Corticostriatal Pathways: Longitudinal Impact on Family Formation and Child Well-Being. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Abraham, E., Gilam, G., Kanat-Maymon, Y., Jacob, Y., Zagoory-Sharon, O., Hendler, T., Feldman, R. 2017

  Abstract

  Alloparental care, the cooperative care of offspring by group members other than the biological mother, has been widely practiced since early hominin evolution to increase infant survival and thriving. The coparental bond-a relationship of solidarity and commitment between two adults who join their effort to care for children-is a central contributor to children's well-being and sociality; yet, the neural basis of coparenting has not been studied in humans. Here, we followed 84 first-time co-parents (42 couples) across the first 6 years of family formation, including opposite-sex and same-sex couples, measured brain response to coparental stimuli, observed collaborative and undermining coparental behaviors in infancy and preschool, assayed oxytocin (OT) and vasopressin (AVP), and measured coparenting and child behavior problems at 6 years. Across family types, coparental stimuli activated the striatum, specifically the ventral striatum and caudate, striatal nodes implicated in motivational goal-directed social behavior. Psychophysiological interaction analysis indicated that both nodes were functionally coupled with the vmPFC in support of the human coparental bond and this connectivity was stronger as collaborative coparental behavior increased. Furthermore, caudate functional connectivity patterns differentiated distinct corticostriatal pathways associated with two stable coparental behavioral styles; stronger caudate-vmPFC connectivity was associated with more collaborative coparenting and was linked to OT, whereas a stronger caudate-dACC connectivity was associated with increase in undermining coparenting and was related to AVP. Finally, dyadic path-analysis model indicated that the parental caudate-vmPFC connectivity in infancy predicted lower child externalizing symptoms at 6 years as mediated by collaborative coparenting in preschool. Findings indicate that the coparental bond is underpinned by striatal activations and corticostriatal connectivity similar to other human affiliative bonds; highlight specific corticostriatal pathways as defining distinct coparental orientations that underpin family life; chart brain-hormone-behavior constellations for the mature, child-orientated coparental bond; and demonstrate the flexibility of this bond across family constellations and its unique contribution to child well-being.Neuropsychopharmacology advance online publication, 17 May 2017; doi:10.1038/npp.2017.71.

  View details for DOI 10.1038/npp.2017.71

  View details for PubMedID 28401924

• Accessible Neurobehavioral Anger-Related Markers for Vulnerability to Post-Traumatic Stress Symptoms in a Population of Male Soldiers FRONTIERS IN BEHAVIORAL NEUROSCIENCE Lin, T., Gilam, G., Raz, G., Or-Borichev, A., Bar-Haim, Y., Fruchter, E., Hendler, T. 2017; 11

  Abstract

  Identifying vulnerable individuals prone to develop post-traumatic stress symptoms (PTSS) is of paramount importance, especially in populations at high risk for stress exposure such as combat soldiers. While several neural and psychological risk factors are known, no post-traumatic stress disorder (PTSD) biomarker has yet progressed to clinical use. Here we present novel and clinically applicable anger-related neurobehavioral risk markers for military-related PTSS in a large cohort of Israeli soldiers. The psychological, electrophysiological and neural (Simultaneous recording of scalp electroencephalography [EEG] and functional magnetic resonance imaging [fMRI]) reaction to an anger-inducing film were measured prior to advanced military training and PTSS were recorded at 1-year follow-up. Limbic modulation was measured using a novel approach that monitors amygdala modulation using fMRI-inspired EEG, hereafter termed amygdala electrical fingerprint (amyg-EFP). Inter-subject correlation (ISC) analysis on fMRI data indicated that during movie viewing participants' brain activity was synchronized in limbic regions including the amygdala. Self-reported state-anger and amyg-EFP modulation successfully predicted PTSS levels. State-anger significantly accounted for 20% of the variance in PTSS, and amyg-EFP signal modulation significantly accounted for additional 15% of the variance. Our study was limited by the moderate PTSS levels and lack of systematic baseline symptoms assessment. These results suggest that pre-stress neurobehavioral measures of anger may predict risk for later PTSS, pointing to anger-related vulnerability factors that can be measured efficiently and at a low cost before stress exposure. Possible mechanisms underlying the association between the anger response and risk for PTSS are discussed.

  View details for DOI 10.3389/fnbeh.2017.00038

  View details for Web of Science ID 000395440400002

  View details for PubMedID 28326027

  View details for PubMedCentralID PMC5339223

• The role of oxytocin in modulating interpersonal space: A pharmacological fMRI study PSYCHONEUROENDOCRINOLOGY Cohen, D., Perry, A., Gilam, G., Mayseless, N., Gonen, T., Hendler, T., Shamay-Tsoory, S. G. 2017; 76: 77-83

  Abstract

  Interpersonal space is a nonverbal indicator of affiliation and closeness. In this study we investigated the effects of oxytocin (OT), a neuropeptide known for its social role in humans, on interpersonal space. In a double blind placebo controlled study we measured the effect of intranasal OT on the personal distance preferences of different familiar (friend) and unfamiliar (stranger) protagonists. Behavioral results showed that participants preferred to be closer to a friend than to a stranger. Intranasal OT was associated with an overall distancing effect, but this effect was significant for the stranger and not for the friend. The imaging results showed interactions between treatment (OT, placebo) and protagonist (friend, stranger) in regions that mediate social behavior including the dorsomedial prefrontal cortex (dmPFC), a region associated with the mentalizing system. Specifically, OT increased activity in the dmPFC when a friend approached the participants but not when a stranger approached. The results indicate that the effect of OT on interpersonal space greatly depends on the participant's relationship with the protagonist. This supports the social salience theory, according to which OT increases the salience of social cues depending on the context.

  View details for DOI 10.1016/j.psyneuen.2016.10.021

  View details for Web of Science ID 000393723600011

  View details for PubMedID 27889465

• Deconstructing Anger in the Human Brain. Current topics in behavioral neurosciences Gilam, G., Hendler, T. 2017; 30: 257-273

  Abstract

  Anger may be caused by a wide variety of triggers, and though it has negative consequences on health and well-being, it is also crucial in motivating to take action and approach rather than avoid a confrontation. While anger is considered a survival response inherent in all living creatures, humans are endowed with the mental flexibility that enables them to control and regulate their anger, and adapt it to socially accepted norms. Indeed, a profound interpersonal nature is apparent in most events which evoke anger among humans. Since anger consists of physiological, cognitive, subjective, and behavioral components, it is a contextualized multidimensional construct that poses theoretical and operational difficulties in defining it as a single psychobiological phenomenon. Although most neuroimaging studies have neglected the multidimensionality of anger and thus resulted in brain activations dispersed across the entire brain, there seems to be several reoccurring neural circuits subserving the subjective experience of human anger. Nevertheless, to capture the large variety in the forms and fashions in which anger is experienced, expressed, and regulated, and thus to better portray the related underlying neural substrates, neurobehavioral investigations of human anger should aim to further embed realistic social interactions within their anger induction paradigms.

  View details for DOI 10.1007/7854_2015_408

  View details for PubMedID 26695163

• Common modulation of limbic network activation underlies musical emotions as they unfold NEUROIMAGE Singer, N., Jacoby, N., Lin, T., Raz, G., Shpigelman, L., Gilam, G., Granot, R. Y., Hendler, T. 2016; 141: 517-529

  Abstract

  Music is a powerful means for communicating emotions among individuals. Here we reveal that this continuous stream of affective information is commonly represented in the brains of different listeners and that particular musical attributes mediate this link. We examined participants' brain responses to two naturalistic musical pieces using functional Magnetic Resonance imaging (fMRI). Following scanning, as participants listened to the musical pieces for a second time, they continuously indicated their emotional experience on scales of valence and arousal. These continuous reports were used along with a detailed annotation of the musical features, to predict a novel index of Dynamic Common Activation (DCA) derived from ten large-scale data-driven functional networks. We found an association between the unfolding music-induced emotionality and the DCA modulation within a vast network of limbic regions. The limbic-DCA modulation further corresponded with continuous changes in two temporal musical features: beat-strength and tempo. Remarkably, this "collective limbic sensitivity" to temporal features was found to mediate the link between limbic-DCA and the reported emotionality. An additional association with the emotional experience was found in a left fronto-parietal network, but only among a sub-group of participants with a high level of musical experience (>5years). These findings may indicate two processing-levels underlying the unfolding of common music emotionality; (1) a widely shared core-affective process that is confined to a limbic network and mediated by temporal regularities in music and (2) an experience based process that is rooted in a left fronto-parietal network that may involve functioning of the 'mirror-neuron system'.

  View details for DOI 10.1016/j.neuroimage.2016.07.002

  View details for Web of Science ID 000384074500044

  View details for PubMedID 27389788

• Limbic Activity Modulation Guided by Functional Magnetic Resonance Imaging-Inspired Electroencephalography Improves Implicit Emotion Regulation BIOLOGICAL PSYCHIATRY Keynan, J. N., Meir-Hasson, Y., Gilam, G., Cohen, A., Jackont, G., Kinreich, S., Ikar, L., Or-Borichev, A., Etkin, A., Gyurak, A., Klovatch, I., Intrator, N., Hendler, T. 2016; 80 (6): 490-496

  Abstract

  The amygdala has a pivotal role in processing traumatic stress; hence, gaining control over its activity could facilitate adaptive mechanism and recovery. To date, amygdala volitional regulation could be obtained only via real-time functional magnetic resonance imaging (fMRI), a highly inaccessible procedure. The current article presents high-impact neurobehavioral implications of a novel imaging approach that enables bedside monitoring of amygdala activity using fMRI-inspired electroencephalography (EEG), hereafter termed amygdala-electrical fingerprint (amyg-EFP). Simultaneous EEG/fMRI indicated that the amyg-EFP reliably predicts amygdala-blood oxygen level-dependent activity. Implementing the amyg-EFP in neurofeedback demonstrated that learned downregulation of the amyg-EFP facilitated volitional downregulation of amygdala-blood oxygen level-dependent activity via real-time fMRI and manifested as reduced amygdala reactivity to visual stimuli. Behavioral evidence further emphasized the therapeutic potential of this approach by showing improved implicit emotion regulation following amyg-EFP neurofeedback. Additional EFP models denoting different brain regions could provide a library of localized activity for low-cost and highly accessible brain-based diagnosis and treatment.

  View details for DOI 10.1016/j.biopsych.2015.12.024

  View details for Web of Science ID 000382260500015

  View details for PubMedID 26996601

• With love, from me to you: Embedding social interactions in affective neuroscience NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS Gilam, G., Hendler, T. 2016; 68: 590-601

  Abstract

  Human emotional experiences naturally occur while interacting in a spontaneous, dynamic and response contingent fashion with other humans. This resonates with both theoretical considerations as well as neuroimaging findings that illustrate the nexus between the "social" and "emotional" brain suggesting a domain-general organization of the brain. Nevertheless, most knowledge in affective neuroscience stems from studying the brain in isolation from its natural social environment. Whether social interactions are constitutive or not to the understanding of other people's intentions, incorporating such interactions is clearly required for ecological validity. Moreover, since interpersonal interactions may influence emotional experiences and expressions, interactive paradigms may advance the theoretical understanding of what emotions are and what about them is social, and will correspondingly characterize their underlying neural substrates. We highlight the recent conceptual and experimental advances of bringing realistic social interactions into the neuroimaging lab; review emotion-induction paradigms and consider their congruency with features of social interactions; and emphasize the importance of embedding such spontaneous and dynamic interactive paradigms in the field of affective neuroscience.

  View details for DOI 10.1016/j.neubiorev.2016.06.027

  View details for Web of Science ID 000383293500040

  View details for PubMedID 27339690

• Functional connectivity dynamics during film viewing reveal common networks for different emotional experiences COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Raz, G., Touroutoglou, A., Wilson-Mendenhall, C., Gilam, G., Lin, T., Gonen, T., Jacob, Y., Atzil, S., Admon, R., Bleich-Cohen, M., Maron-Katz, A., Hendler, T., Barrett, L. F. 2016; 16 (4): 709-723

  Abstract

  Recent theoretical and empirical work has highlighted the role of domain-general, large-scale brain networks in generating emotional experiences. These networks are hypothesized to process aspects of emotional experiences that are not unique to a specific emotional category (e.g., "sadness," "happiness"), but rather that generalize across categories. In this article, we examined the dynamic interactions (i.e., changing cohesiveness) between specific domain-general networks across time while participants experienced various instances of sadness, fear, and anger. We used a novel method for probing the network connectivity dynamics between two salience networks and three amygdala-based networks. We hypothesized, and found, that the functional connectivity between these networks covaried with the intensity of different emotional experiences. Stronger connectivity between the dorsal salience network and the medial amygdala network was associated with more intense ratings of emotional experience across six different instances of the three emotion categories examined. Also, stronger connectivity between the dorsal salience network and the ventrolateral amygdala network was associated with more intense ratings of emotional experience across five out of the six different instances. Our findings demonstrate that a variety of emotional experiences are associated with dynamic interactions of domain-general neural systems.

  View details for DOI 10.3758/s13415-016-0425-4

  View details for Web of Science ID 000380116000011

  View details for PubMedID 27142636

• The Dark Side of Gendered Language: The Masculine-Generic Form as a Cause for Self-Report Bias PSYCHOLOGICAL ASSESSMENT Vainapel, S., Shamir, O. Y., Tenenbaum, Y., Gilam, G. 2015; 27 (4): 1513-1519

  Abstract

  Language reflects sociocultural structures, such as gender, and affects individuals' perceptions and cognitions. In gendered languages, male-inflected parts of speech are generally used for both sexes (i.e., masculine generics), thus proliferating stereotypes, inequality, and misattributions. We hypothesized that masculine-generic inflection in a questionnaire would bias women's reports compared with a gender-neutral inflection (e.g., "he or she"). We tested our prediction using an academic motivation questionnaire. We found that women reported lower task value and intrinsic goal orientation in the masculine-generic form compared with the gender-neutral form, and lower self-efficacy than men in the masculine-generic form. These findings suggest that questionnaires and surveys written in gendered languages or translated into them may contain construct-irrelevant variance that may undermine the validity of their scores' interpretations, thus risking the possibility of false conclusions.

  View details for DOI 10.1037/pas0000156

  View details for Web of Science ID 000366820900036

  View details for PubMedID 25984637

• Neural substrates underlying the tendency to accept anger-infused ultimatum offers during dynamic social interactions NEUROIMAGE Gilam, G., Lin, T., Raz, G., Azrielant, S., Fruchter, E., Ariely, D., Hendler, T. 2015; 120: 400-411

  Abstract

  In managing our way through interpersonal conflict, anger might be crucial in determining whether the dispute escalates to aggressive behaviors or resolves cooperatively. The Ultimatum Game (UG) is a social decision-making paradigm that provides a framework for studying interpersonal conflict over division of monetary resources. Unfair monetary UG-offers elicit anger and while accepting them engages regulatory processes, rejecting them is regarded as an aggressive retribution. Ventro-medial prefrontal-cortex (vmPFC) activity has been shown to relate to idiosyncratic tendencies in accepting unfair offers possibly through its role in emotion regulation. Nevertheless, standard UG paradigms lack fundamental aspects of real-life social interactions in which one reacts to other people in a response contingent fashion. To uncover the neural substrates underlying the tendency to accept anger-infused ultimatum offers during dynamic social interactions, we incorporated on-line verbal negotiations with an obnoxious partner in a repeated-UG during fMRI scanning. We hypothesized that vmPFC activity will differentiate between individuals with high or low monetary gains accumulated throughout the game and reflect a divergence in the associated emotional experience. We found that as individuals gained more money, they reported less anger but also more positive feelings and had slower sympathetic response. In addition, high-gain individuals had increased vmPFC activity, but also decreased brainstem activity, which possibly reflected the locus coeruleus. During the more angering unfair offers, these individuals had increased dorsal-posterior Insula (dpI) activity which functionally coupled to the medial-thalamus (mT). Finally, both vmPFC activity and dpI-mT connectivity contributed to increased gain, possibly by modulating the ongoing subjective emotional experience. These ecologically valid findings point towards a neural mechanism that might nurture pro-social interactions by modulating an individual's dynamic emotional experience.

  View details for DOI 10.1016/j.neuroimage.2015.07.003

  View details for Web of Science ID 000362025000036

  View details for PubMedID 26166623

• Portraying emotions at their unfolding: A multilayered approach for probing dynamics of neural networks NEUROIMAGE Raz, G., Winetraub, Y., Jacob, Y., Kinreich, S., Maron-Katz, A., Shaham, G., Podlipsky, I., Gilam, G., Soreq, E., Hendler, T. 2012; 60 (2): 1448-1461

  Abstract

  Dynamic functional integration of distinct neural systems plays a pivotal role in emotional experience. We introduce a novel approach for studying emotion-related changes in the interactions within and between networks using fMRI. It is based on continuous computation of a network cohesion index (NCI), which is sensitive to both strength and variability of signal correlations between pre-defined regions. The regions encompass three clusters (namely limbic, medial prefrontal cortex (mPFC) and cognitive), each previously was shown to be involved in emotional processing. Two sadness-inducing film excerpts were viewed passively, and comparisons between viewer's rated sadness, parasympathetic, and inter-NCI and intra-NCI were obtained. Limbic intra-NCI was associated with reported sadness in both movies. However, the correlation between the parasympathetic-index, the rated sadness and the limbic-NCI occurred in only one movie, possibly related to a "deactivated" pattern of sadness. In this film, rated sadness intensity also correlated with the mPFC intra-NCI, possibly reflecting temporal correspondence between sadness and sympathy. Further, only for this movie, we found an association between sadness rating and the mPFC-limbic inter-NCI time courses. To the contrary, in the other film in which sadness was reported to commingle with horror and anger, dramatic events coincided with disintegration of these networks. Together, this may point to a difference between the cinematic experiences with regard to inter-network dynamics related to emotional regulation. These findings demonstrate the advantage of a multi-layered dynamic analysis for elucidating the uniqueness of emotional experiences with regard to an unguided processing of continuous and complex stimulation.

  View details for DOI 10.1016/j.neuroimage.2011.12.084

  View details for Web of Science ID 000303272300057

  View details for PubMedID 22285693

• The Envious Brain: The Neural Basis of Social Comparison HUMAN BRAIN MAPPING Dvash, J., Gilam, G., Ben-Ze'ev, A., Hendler, T., Shamay-Tsoory, S. G. 2010; 31 (11): 1741-1750

  Abstract

  Humans have a drive to evaluate themselves by examining their abilities and outcomes in comparison to others. The present study examined the emotional and neural correlates of upward social comparison (comparison with those who have more) and downward social comparison (comparison with those who have less). Two experiments were conducted with volunteers in an interactive game of chance, in which a putative player won or lost more money than the participant. The results showed that even when participants lost money, they expressed joy and schadenfreude (gloating) if the other player had lost more money. On the other hand when they actually won money, but the other player had won more they expressed envy. This pattern was also demonstrated in a differential BOLD response in the ventral striatum. Comparing the activations between an actual gain and a relative gain indicated that even when a person loses money, merely adding information about another person's greater loss may increase ventral striatum activations to a point where these activations are similar to those of an actual gain. We suggest that the ventral striatum plays a role in mediating the emotional consequences of social comparison.

  View details for DOI 10.1002/hbm.20972

  View details for Web of Science ID 000283641100010

  View details for PubMedID 20205244