Modulating what is and what could have been: The effect of transcranial direct current stimulation on the evaluation of attained and unattained decision outcomes.

The affective evaluation of decision outcomes, whether attained (e.g., disappointment) or based on the conscious realization that a decision made differently would have led to a better or worse outcome (e.g., regret), greatly influence future decisions. Prior research has demonstrated a role of the medial and orbitofrontal cortex (M/OFC) in decision valuation and the experience of regret and relief. Here we examined whether inhibitory transcranial direct current stimulation (tDCS) could dampen the experience of decision-induced affect, with a focus on regret and relief. Thirty-eight participants completed a previously used gambling task and were asked to rate their happiness with attained outcomes of a chosen gamble before and after being shown unattained, counterfactual outcomes (i.e., what would have happened had they selected the other gamble). The difference in happiness rating before and after revealing these unattained counterfactual outcomes was taken as a measure of regret (negative shift) or relief (positive shift). During this task, 20 participants received 2 mA cathodal tDCS over EEG coordinate Fp1 for 20 minutes, and 18 participants received sham stimulation over the same location. Linear mixed-model results showed that, compared to sham, participants who received cathodal tDCS reported less intense emotions in response to attained as well as counterfactual outcomes. These findings were not due to the groups differing in the gambles they selected or attained monetary outcomes, demonstrating that tDCS can modulate decision-induced (counterfactual) affect. This may have implications for the ability to modulate value-based decision-making using brain stimulation techniques more broadly.

Skin Conductance Reactivity to Standardized Virtual Reality Combat Scenes in Veterans with PTSD.

Interest in virtual reality (VR) as a clinical tool to augment posttraumatic stress (PTSD) treatment has grown substantially in recent years due to advances in VR technology. Moreover, its potential assisted use in the PTSD diagnostic process has been recognized. In this study we examined physiological responding, skin conductance, to a standardized presentation of non-personalized combat-related VR events (e.g. encountering enemy fire; explosions) as compared to non-combat classroom VR events in 19 Veterans with and 24 Veterans without combat-related PTSD who had been deployed to Iraq and Afghanistan. Veterans watched a total of 12 VR scenarios-six combat-related and six non-combat-related-with each scenario gradually increasing in emotional intensity by adding more VR events in addition to repeating prior VR events. Results show that Veterans with PTSD displayed larger skin conductance reactivity across VR combat events, but not for non-combat VR events, as compared to combat Veterans without PTSD. Nevertheless, Veterans with and without PTSD showed a similar reduction of emotional arousal to repeated presentation of the same VR combat events. Within the PTSD sample, the elevated level of VR combat-related arousal correlated marginally with severity of hyperarousal symptoms. This study confirms that the use of a non-personalized and standardized VR presentation successfully distinguishes Veterans with PTSD from those without on a measure of psychophysiological arousal to combat-related VR stimuli. The assessment of physiological reactivity during the repeated presentation of standardized, trauma-related VR events highlights its use for PTSD assessment as well as treatment.

Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder.

BACKGROUND: Abnormalities in fear extinction and recall are core components of posttraumatic stress disorder (PTSD). Data from animal and human studies point to a role of the ventromedial prefrontal cortex (vmPFC) in extinction learning and subsequent retention of extinction memories. Given the increasing interest in developing noninvasive brain stimulation protocols for psychopathology treatment, we piloted whether transcranial direct current stimulation (tDCS) during extinction learning, vs. during consolidation of extinction learning, might improve extinction recall in veterans with warzone-related PTSD. METHODS: Twenty-eight veterans with PTSD completed a 2-day Pavlovian fear conditioning, extinction, and recall paradigm. Participants received one 10-min session of 2 mA anodal tDCS over AF3, intended to target the vmPFC. Fourteen received tDCS that started simultaneously with extinction learning onset, and the remaining 14 participants received tDCS during extinction consolidation. Normalized skin conductance reactivity (SCR) was the primary outcome measure. Linear mixed effects models were used to test for effects of tDCS on late extinction and early extinction recall 24 hr later. RESULTS: During early recall, veterans who received tDCS during extinction consolidation showed slightly lower SCR in response to previously extinguished stimuli as compared to veterans who received tDCS simultaneous with extinction learning (p = .08), generating a medium effect size (Cohen's d = .38). There was no significant effect of tDCS on SCR during late extinction. CONCLUSIONS: These preliminary findings suggest that testing the effects of tDCS during consolidation of fear extinction may have promise as a way of enhancing extinction recall.

The influence of cooperation and defection on social decision making in depression: A study of the iterated Prisoner's Dilemma Game.

This study evaluated the influence of self-reported levels of depression on interpersonal strategic decision making when interacting with partners who differed in their predetermined tendency to cooperate in three separate computerized iterated Prisoner's Dilemma Games (iPDGs). Across 29 participants, cooperation was lowest when interacting with a predominantly defecting partner and highest when interacting with a predominantly cooperating partner. Greater depression severity was related to steadier and continued cooperation over trials with the cooperating partner, seeming to reflect a prosocial response tendency when interacting with this partner. With the unbiased partner, depression severity was associated with a more volatile response pattern in reaction to cooperation and defection by this partner. Severity of depression did not influence cooperation with a defecting partner or expectations about partner cooperation reported before the task began. Taken together, these data appear to show that in predominately positive interactions, as in the cooperating partner condition, depression is associated with less volatile, more consistent cooperation. When such clear feedback is absent, as in the unbiased partner condition, depression is associated with more volatile behavior. Nonetheless, participants were generally able to adapt their behavior accordingly in this dynamic interpersonal decision making context.

Deficits in Degraded Facial Affect Labeling in Schizophrenia and Borderline Personality Disorder.

Although deficits in facial affect processing have been reported in schizophrenia as well as in borderline personality disorder (BPD), these disorders have not yet been directly compared on facial affect labeling. Using degraded stimuli portraying neutral, angry, fearful and angry facial expressions, we hypothesized more errors in labeling negative facial expressions in patients with schizophrenia compared to healthy controls. Patients with BPD were expected to have difficulty in labeling neutral expressions and to display a bias towards a negative attribution when wrongly labeling neutral faces. Patients with schizophrenia (N = 57) and patients with BPD (N = 30) were compared to patients with somatoform disorder (SoD, a psychiatric control group; N = 25) and healthy control participants (N = 41) on facial affect labeling accuracy and type of misattributions. Patients with schizophrenia showed deficits in labeling angry and fearful expressions compared to the healthy control group and patients with BPD showed deficits in labeling neutral expressions compared to the healthy control group. Schizophrenia and BPD patients did not differ significantly from each other when labeling any of the facial expressions. Compared to SoD patients, schizophrenia patients showed deficits on fearful expressions, but BPD did not significantly differ from SoD patients on any of the facial expressions. With respect to the type of misattributions, BPD patients mistook neutral expressions more often for fearful expressions compared to schizophrenia patients and healthy controls, and less often for happy compared to schizophrenia patients. These findings suggest that although schizophrenia and BPD patients demonstrate different as well as similar facial affect labeling deficits, BPD may be associated with a tendency to detect negative affect in neutral expressions.

Can Transcranial Direct Current Stimulation Augment Extinction of Conditioned Fear?

BACKGROUND: Exposure-based therapy parallels extinction learning of conditioned fear. Prior research points to the ventromedial prefrontal cortex as a potential site for the consolidation of extinction learning and subsequent retention of extinction memory. OBJECTIVE/HYPOTHESIS: The present study aimed to evaluate whether the application of non-invasive transcranial direct current stimulation (tDCS) during extinction learning enhances late extinction and early recall in human participants. METHODS: Forty-four healthy volunteers completed a 2-day Pavlovian fear conditioning, extinction, and recall paradigm while skin conductance activity was continuously measured. Twenty-six participants received 2 mA anodal tDCS over EEG coordinate AF3 during extinction of a first conditioned stimulus. The remaining 18 participants received similar tDCS during extinction of a second conditioned stimulus. Sham stimulation was applied for the balance of extinction trials in both groups. Normalized skin conductance changes were analyzed using linear mixed models to evaluate effects of tDCS over late extinction and early recall trials. RESULTS: We observed a significant interaction between timing of tDCS during extinction blocks and changes in skin conductance reactivity over late extinction trials. These data indicate that tDCS was associated with accelerated late extinction learning of a second conditioned stimulus after tDCS was combined with extinction learning of a previous conditioned stimulus. No significant effects of tDCS timing were observed on early extinction recall. CONCLUSIONS: Results could be explained by an anxiolytic aftereffect of tDCS and extend previous studies on tDCS-induced modulation of fear and threat related learning processes. These findings support further exploration of the clinical use of tDCS.

Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers.

OBJECTIVE: Current chronic pain treatments target nociception rather than affective "suffering" and its associated functional and psychiatric comorbidities. The left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can non-invasively modulate cortical activity. The present study tests whether anodal tDCS targeting the left DLPFC will increase tolerability of acute painful stimuli vs cathodal tDCS. METHODS: Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting the left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. RESULTS: Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (allP > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal vs cathodal tDCS (P = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (P = 0.042) on CP threshold, suggesting task sensitization. CONCLUSIONS: Although our results do not suggest that polarity of tDCS targeting the left DLPFC differentially modulates the tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting the left dorsal anterior cingulate cortex showed a trend toward higher mean CP tolerance with cathodal vs anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by the DVPRS. Sham-controlled clinical studies are needed.

Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Distress Tolerance: A Preliminary Study.

OBJECTIVE: Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal ("inhibitory") stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli vs anodal stimulation. METHODS: Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. RESULTS: Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal vs anodal stimulation (P = 0.055) for participants self-completing the task. Pressure algometer (P = 0.81) and breath holding tolerance (P = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all P < 0.008). Pain intensity ratings increased acutely after cold pressor and pressure algometer tasks (both P < 0.01), but not after breath holding (P = 0.099). Cold pressor pain ratings tended to rise less after cathodal vs anodal tDCS (P = 0.072). CONCLUSIONS: Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation.

Does interoceptive awareness affect the ability to regulate unfair treatment by others?

In this study we aimed to investigate how awareness of bodily responses, referred to as interoceptive awareness, influences decision-making in a social interactive context. Interoceptive awareness is thought to be crucial for adequate regulation of one's emotions. However, there is a dearth of studies that examine the association between interoceptive awareness and the ability to regulate emotions during interpersonal decision-making. Here, we quantified interoceptive awareness with a heartbeat detection task in which we measured the difference between subjective self-reports and an objective psychophysiological measurement of participant heart rates. Social decision-making was quantified using a two-round Ultimatum Game. Participants were asked to first reject or accept an unfair division of money proposed by a partner. In turn, participants could then make an offer on how to divide an amount of money with the same partner. Participants performed 20 rounds of the two-round Ultimatum Game twice, once during baseline condition and once while asked to reappraise emotional reactions when confronted with unfair offers from partners. Results showed that after reappraisal participants (1) accepted more unfair offers and (2) offered higher return divisions, as compared to baseline. With respect to interoceptive awareness, participants with better heartbeat detection scores tended to report less emotional involvement when they applied reappraisal while playing the Ultimatum Game. However, there was no reliably significant relationship between heartbeat detection and the acceptance of unfair offers. Similarly, heartbeat detection accuracy was not related to return offers made in the second round of the Ultimatum Game or the habitual use of emotion regulation. These preliminary findings suggest that the relationship between interoceptive awareness and behavioral changes due to emotion regulation in a social decision-making context appears to be complex.

Reappraising the ultimatum: an fMRI study of emotion regulation and decision making.

Emotion regulation strategies provide a means by which to modulate our social behavior. In this study, we investigated the effect of using reappraisal to both up- and downregulate social decision making. After being instructed on how to use reappraisal, participants played the Ultimatum Game while undergoing functional magnetic resonance imaging and applied the strategies of upregulation (reappraising the proposer's intentions as more negative), down-regulation (reappraising the proposer's intentions as less negative), as well as a baseline "look" condition. As hypothesized, when reappraising, decision acceptance rates were altered, with a greater number of unfair offers accepted while down-regulating and a greater number of unfair offers rejected while upregulating, both relative to the baseline condition. At the neural level, during reappraisal, significant activations were observed in the inferior and middle frontal gyrus (MFG), in addition to the medial prefrontal cortex and cingulate gyrus for unfair offers only. Regulated decisions involved left inferior frontal gyrus for upregulation and MFG for down-regulation strategies, respectively. Importantly, the effects of emotion modulation were evident in posterior insula, with less activation for down-regulation and more activation for upregulation in these areas. Notably, we show for the first time that top-down strategies such as reappraisal strongly affect our socioeconomic decisions.

The neural mechanisms of affect infusion in social economic decision-making: a mediating role of the anterior insula.

Though emotions have been shown to have sometimes dramatic effects on decision-making, the neural mechanisms mediating these biases are relatively unexplored. Here, we investigated how incidental affect (i.e. emotional states unrelated to the decision at hand) may influence decisions, and how these biases are implemented in the brain. Nineteen adult participants made decisions which involved accepting or rejecting monetary offers from others in an Ultimatum Game while undergoing functional magnetic resonance imaging (fMRI). Prior to each set of decisions, participants watched a short video clip aimed at inducing either a sad or neutral emotional state. Results demonstrated that, as expected, sad participants rejected more unfair offers than those in the neutral condition. Neuroimaging analyses revealed that receiving unfair offers while in a sad mood elicited activity in brain areas related to aversive emotional states and somatosensory integration (anterior insula) and to cognitive conflict (anterior cingulate cortex). Sad participants also showed a diminished sensitivity in neural regions associated with reward processing (ventral striatum). Importantly, insular activation uniquely mediated the relationship between sadness and decision bias. This study is the first to reveal how subtle mood states can be integrated at the neural level to influence decision-making.

Interactive decision-making in people with schizotypal traits: a game theory approach.

Studies that have investigated whether deficits in social cognition observed in schizophrenia are also present in schizotypal individuals have largely been inconclusive, and none of these studies have examined social interactive behavior. Here, we investigated interactive decision-making behavior in individuals differing in the amount of schizotypal symptoms using tasks derived from Game Theory. In total 1691 undergraduate students were screened with the Schizotypal Personality Questionnaire-Brief version. We selected 69 people distributed across the full schizotypal continuum to participate in Ultimatum and Dictator Games in which they played against human and non-human, computer partners. The results showed that higher levels of schizotypal symptoms, particularly positive and disorganized schizotypy, were related to proposing higher offers to all partners. Additionally, the amount of interpersonal schizotypal symptoms was associated with an increased acceptance rate of very unfair offers from human partners, possibly reflecting a blunted emotional response to such offers. We conclude that positive and disorganized schizotypal symptoms are associated with less adequate bargaining behavior, similar to what has been recently observed in patients with schizophrenia. The observed similarities on Ultimatum Game behavior between patients with schizophrenia and individuals with more schizotypal symptoms contribute to the growing evidence that social cognitive deficits may represent a marker of vulnerability to schizophrenia.

The influence of emotion regulation on social interactive decision-making.

Although adequate emotion regulation is considered to be essential in every day life, it is especially important in social interactions. However, the question as to what extent two different regulation strategies are effective in changing decision-making in a consequential socially interactive context remains unanswered. We investigated the effect of expressive suppression and emotional reappraisal on strategic decision-making in a social interactive task, that is, the Ultimatum Game. As hypothesized, participants in the emotional reappraisal condition accepted unfair offers more often than participants in the suppression and no-regulation condition. Additionally, the effect of emotional reappraisal influenced the amount of money participants proposed during a second interaction with partners that had treated them unfairly in a previous interaction. These results support and extend previous findings that emotional reappraisal as compared to expressive suppression, is a powerful regulation strategy that influences and changes how we interact with others even in the face of inequity.

Seeing is believing: trustworthiness as a dynamic belief.

Recent efforts to understand the mechanisms underlying human cooperation have focused on the notion of trust, with research illustrating that both initial impressions and previous interactions impact the amount of trust people place in a partner. Less is known, however, about how these two types of information interact in iterated exchanges. The present study examined how implicit initial trustworthiness information interacts with experienced trustworthiness in a repeated Trust Game. Consistent with our hypotheses, these two factors reliably influence behavior both independently and synergistically, in terms of how much money players were willing to entrust to their partner and also in their post-game subjective ratings of trustworthiness. To further understand this interaction, we used Reinforcement Learning models to test several distinct processing hypotheses. These results suggest that trustworthiness is a belief about probability of reciprocation based initially on implicit judgments, and then dynamically updated based on experiences. This study provides a novel quantitative framework to conceptualize the notion of trustworthiness.

Emotion regulation strategies in patients with schizophrenia.

Schizophrenia patients might experience difficulties in applying two widely used emotion regulation strategies, reappraisal and suppression. We investigated the relationships among emotion regulation strategies, alexithymia (i.e. inability to identify and verbalize feelings) and the role of pre-morbid IQ on alexithymia in schizophrenia. Participants comprised 31 schizophrenia patients and 44 healthy subjects who were tested on measures of emotion regulation strategies (ERQ), alexithymia (BVAQ) and pre-morbid IQ (NART). Patients reported significantly more use of suppression strategies and tended to use reappraisal strategies less frequently. Patients differed significantly on the cognitive-emotional component of alexithymia. This difference remained significant even with pre-morbid IQ as a covariate, but disappeared with depression as a covariate. Schizophrenia patients have specific difficulties identifying their feelings. These difficulties were related to symptoms of depression. Interventions specifically targeted at affect regulation and recognition of emotional state could promote emotional well-being in schizophrenia patients.

Involuntary interpretation of social cues is compromised in autism spectrum disorders.

A new social distance judgment task was used to measure quantitatively the extent to which social cues are immediately and involuntary interpreted by typically developing (TD) individuals and by individuals with autism spectrum disorders (ASD). The task thus tapped into the ability to involuntary "pick up" the meaning of social cues. The cues tested were social attention and implied biological motion. Task performance of the ASD and TD groups was similarly affected by a perceptual low-level illusion induced by physical characteristics of the stimuli. In contrast, a high-level illusion induced by the implications of the social cues affected only the TD individuals; the ASD individuals remained unaffected (causing them to perform superior to TD controls). The results indicate that despite intact perceptual processing, the immediate involuntary interpretation of social cues can be compromised. We propose that this type of social cue understanding is a distinct process that should be differentiated from reflective social cue understanding and is specifically compromised in ASD. We discuss evidence for an underpinning neural substrate.

Deficits in implicit attention to social signals in schizophrenia and high risk groups: behavioural evidence from a new illusion.

BACKGROUND: An increasing body of evidence suggests that the apparent social impairments observed in schizophrenia may arise from deficits in social cognitive processing capacities. The ability to process basic social cues, such as gaze direction and biological motion, effortlessly and implicitly is thought to be a prerequisite for establishing successful social interactions and for construing a sense of "social intuition." However, studies that address the ability to effortlessly process basic social cues in schizophrenia are lacking. Because social cognitive processing deficits may be part of the genetic vulnerability for schizophrenia, we also investigated two groups that have been shown to be at increased risk of developing schizophrenia-spectrum pathology: first-degree relatives of schizophrenia patients and men with Klinefelter syndrome (47,XXY). RESULTS: We compared 28 patients with schizophrenia, 29 siblings of patients with schizophrenia, and 29 individuals with Klinefelter syndrome with 46 matched healthy control subjects on a new paradigm. This paradigm measures one's susceptibility for a bias in distance estimation between two agents that is induced by the implicit processing of gaze direction and biological motion conveyed by these agents. Compared to control subjects, patients with schizophrenia, as well as siblings of patients and Klinefelter men, showed a lack of influence of social cues on their distance judgments. CONCLUSIONS: We suggest that the insensitivity for social cues is a cognitive aspect of schizophrenia that may be seen as an endophenotype as it appears to be present both in relatives who are at increased genetic risk and in a genetic disorder at risk for schizophrenia-spectrum psychopathology. These social cue-processing deficits could contribute, in part, to the difficulties in higher order social cognitive tasks and, hence, to decreased social competence that has been observed in these groups.

Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex disrupts digit span task performance.

The digit span task measures the maintenance of information in short-term memory, and is one of the most widely used tests in clinical and experimental neuropsychology. Functional imaging studies have suggested a role of the right dorsolateral prefrontal cortex (DLPFC) in digit span performance. It remains unclear however, whether activation of this area is critical for task performance. Using repetitive transcranial magnetic stimulation (rTMS) over the right DLPFC in a sham-controlled design, we tested the hypothesis of the involvement of the right DLPFC in digit span task performance. We observed a significant disruption of digit span performance in healthy subjects in the real rTMS condition as compared to the sham condition. This effect of rTMS did not differ between digits forward and digits backward. Our results suggest that the right DLPFC is critical for central executive processes utilized by the digits forward and backward tasks.

Fearful faces in schizophrenia: the relationship between patient characteristics and facial affect recognition.

Although schizophrenia has often been associated with deficits in facial affect recognition, it is debated whether the recognition of specific emotions is affected and if these facial affect-processing deficits are related to symptomatology or other patient characteristics. The purpose of the present study was to explore whether particular patient characteristics are associated with the recognition of specific facial expressions in patients with schizophrenia. Sixty-four patients with a DSM-IV diagnosis of schizophrenia were assessed with a computerized test of degraded facial affect recognition. Linear regression analysis showed that, in particular, negative symptoms and male sex were associated with worse recognition of fearful faces. Furthermore, diagnosis of nonparanoid schizophrenia and later age of onset were associated with worse recognition of neutral faces. Findings are explained in the light of a neuroanatomical dysfunction accounting for both negative symptoms, such as reduced emotional expression and social-emotional dysfunction, for which men seem more vulnerable than women.