EEG evidence for racial ingroup bias in collective empathy for pain.

Previous research on racial ingroup bias in empathy for pain focused on neural responses to a single person's suffering. It is unclear whether empathy for simultaneously perceived multiple individuals' pain (denoted as collective empathy in this study) is also sensitive to perceived racial identities of empathy targets. We addressed this issue by recording electroencephalography from Chinese adults who responded to racial identities of 2 × 2 arrays of Asian or White faces in which 4 faces, 1 face, or no face showed painful expressions. Participants reported greater feelings of others' pain and their own unpleasantness when viewing 4 compared to 1 (or no) painful faces. Behavioral responses to racial identities of faces revealed decreased speeds of information acquisition when responding to the face arrays with 4 (vs. 1 or no) painful expressions of Asian (but not White) faces. Moreover, Asian compared to White face arrays with 4 (vs. 1 or no) painful expressions elicited a larger positive neural response at 160-190 ms (P2) at the frontal/central electrodes and enhanced alpha synchronizations at 288-1,000 ms at the central electrodes. Our findings provide evidence for racial ingroup biases in collective empathy for pain and unravel its relevant neural underpinnings.

Shank3 mutations enhance early neural responses to deviant tones in dogs.

Both enhanced discrimination of low-level features of auditory stimuli and mutations of SHANK3 (a gene that encodes a synaptic scaffolding protein) have been identified in autism spectrum disorder patients. However, experimental evidence regarding whether SHANK3 mutations lead to enhanced neural processing of low-level features of auditory stimuli is lacking. The present study investigated this possibility by examining effects of Shank3 mutations on early neural processing of pitch (tone frequency) in dogs. We recorded electrocorticograms from wild-type and Shank3 mutant dogs using an oddball paradigm in which deviant tones of different frequencies or probabilities were presented along with other tones in a repetitive stream (standards). We found that, relative to wild-type dogs, Shank3 mutant dogs exhibited larger amplitudes of early neural responses to deviant tones and greater sensitivity to variations of deviant frequencies within 100 ms after tone onsets. In addition, the enhanced early neural responses to deviant tones in Shank3 mutant dogs were observed independently of the probability of deviant tones. Our findings highlight an essential functional role of Shank3 in modulations of early neural detection of novel sounds and offer new insights into the genetic basis of the atypical auditory information processing in autism patients.

Neural dissociation between reward and salience prediction errors through the lens of optimistic bias.

The question of how the brain represents reward prediction errors is central to reinforcement learning and adaptive, goal-directed behavior. Previous studies have revealed prediction error representations in multiple electrophysiological signatures, but it remains elusive whether these electrophysiological correlates underlying prediction errors are sensitive to valence (in a signed form) or to salience (in an unsigned form). One possible reason concerns the loose correspondence between objective probability and subjective prediction resulting from the optimistic bias, that is, the tendency to overestimate the likelihood of encountering positive future events. In the present electroencephalography (EEG) study, we approached this question by directly measuring participants' idiosyncratic, trial-to-trial prediction errors elicited by subjective and objective probabilities across two experiments. We adopted monetary gain and loss feedback in Experiment 1 and positive and negative feedback as communicated by the same zero-value feedback in Experiment 2. We provided electrophysiological evidence in time and time-frequency domains supporting both reward and salience prediction error signals. Moreover, we showed that these electrophysiological signatures were highly flexible and sensitive to an optimistic bias and various forms of salience. Our findings shed new light on multiple presentations of prediction error in the human brain, which differ in format and functional role.

Blunted neural effects of perceived control on reward feedback in major depressive disorder.

BACKGROUND: Blunted reward processing has emerged as an endophenotype of major depressive disorder (MDD), but mechanistic understanding for this deficit remains elusive. The current event-related potential study examined whether this aberration is driven by the blunted effect of perceived control on reward processing. METHODS: We adapted a well-validated gambling task in which perceived control was exercised by choice in 29 individuals with current MDD and 31 healthy controls. We examined the reward positivity in response to personally chosen versus passively received rewards. RESULTS: We found that MDD patients relative to healthy controls exhibited a blunted reward positivity when rewards were delivered following voluntary choices but not when they were delivered following passive choices. This pattern was not observed during the relatively late stage, as indexed by the P300, of feedback processing. LIMITATION: The current findings may be confounded with medication and anxiety. CONCLUSIONS: These findings suggest that deficient reward processing in MDD is attributable to the deficiency in boosting reward responsivity by perceived control exercised by choice.

Decomposing the effort paradox in reward processing: Time matters.

Effort expenditure not only discounts reward value prospectively but also accrues reward value retrospectively. To decompose the effort paradox in reward processing, the current event-related potential study investigated the neural dynamics underlying effects of effort expenditure on subsequent reward processing. Participants exerted one of two levels of effort to obtain an opportunity of winning a high or low amount of monetary reward, and we focused on electrophysiological activity during the anticipatory and consummatory phases of reward processing. During the anticipatory phase, the stimulus-preceding negativity was enhanced when potential high rewards were anticipated, but this reward effect disappeared following high-effort expenditure. During the consummatory phase, feedback-related ERPs were increased for high relative to low rewards, and this reward effect was enlarged following effort expenditure during the early stage (200-300 ms) as indexed by the reward positivity but not the late stage (400-600 ms) as indexed by the P3. Our findings provide a strong support for the psychological contrast theory and indicate that time matters in decomposing the effort paradox for reward processing such that effort expenditure reduces reward sensitivity during the anticipatory phase but enhances reward sensitivity during the consummatory phase.

Acquisition of temozolomide resistance by the rat C6 glioma cell line increases cell migration and side population phenotype.

Cancer stem cells are reportedly associated with drug resistance in glioma, but there are conflicting findings on the effects of cancer stem cells on drug resistance. The aim of the present study was to identify the underlying mechanisms of drug resistance in rat C6 glioma cells, through the use of Transwell invasion assays, flow cytometric and western blot analyses as well as immunohistochemical staining. The results revealed that acquisition of drug resistance by C6 cells enhanced migration ability in vivo and in vitro. Notably, drug resistance did not depend on the cancer stem cells of C6 cells, but on the increase of a side population phenotype. Blockade of the ABC transporter could increase sensitivity to temozolomide and temozolomide­induced apoptosis in C6 cells. Collectively, these data indicated that drug resistance of C6 cells was mediated by the side population phenotype rather than by cancer stem cells.

Abnormal performance monitoring but intact response inhibition in sensation seeking.

The sensation-seeking trait is a potential endophenotype for various addictive behaviors. Using a nonclinical sample, the current ERP study examined the effects of sensation seeking on performance monitoring and response inhibition. Twenty high sensation seekers and 21 low sensation seekers were selected from a large sample based on their sensation-seeking score and performed a stop-signal task while their EEG was recorded. High relative to low sensation seekers displayed similar response inhibition in terms of performance measure and stop-P3 amplitudes. Compared to low sensation seekers, however, high sensation seekers exhibited a reduced stop-N2 for unsuccessful, but not successful, inhibition. Moreover, an enhanced go-N2 in response to go signals was observed for high versus low sensation seekers, irrespective of whether the go signals were followed by a stop signal or not. Together, our findings suggest that sensation seeking in nonclinical populations is related to individual variability in performance monitoring rather than response inhibition, which provides important implications for the prevention and intervention of addictive behaviors that are driven by trait sensation seeking.

Effects of sensation seeking on habituation to novelty: An EEG study.

Sensation seeking is characterized by a strong need for novelty and has been associated with various risk-taking behaviors. Using the extreme between-group design, the current study investigated the electrophysiological mechanisms underlying habituation to novelty processing in sensation seeking. Twenty high sensation seekers (HSS) and 20 low sensation seekers (LSS) performed an auditory oddball task while their EEG was recorded. The results revealed that both the novelty P3 and midfrontal theta power decreased from the first to the second half for LSS but not for HSS. Additionally, this reduced vigilance was predicted by the experience-seeking subcomponent of sensation seeking. Together, our findings are supportive of an abnormal habituation to novel events in the sensation-seeking trait.

Contextual valence modulates the effect of choice on incentive processing.

Previous research has demonstrated that reward-related neural activity is enhanced for choice relative to no-choice opportunities in the gain context. The current event-related potential study examined whether this modulatory effect of choice can be observed in both the gain and the loss contexts across anticipatory and consummatory phases of incentive processing. Thirty-two participants performed a simple choice task during which choices were made either by themselves (a choice condition) or by a computer (a no-choice condition) during a gain context (gain vs nongain) and a loss context (nonloss vs loss). Behaviorally, participants reported a higher level of perceived control in the choice than the no-choice condition as well as in the gain than loss context. During the anticipatory phase, the choice relative to the no-choice condition elicited an increased cue-P3 in the loss context and an enhanced stimulus-preceding negativity in the gain context. During the consummatory phase, the choice condition elicited a larger reward positivity (ΔRewP) than the no-choice condition in the gain relative to the loss context but a comparable feedback P3 across contexts. These findings demonstrate that the crucial role of voluntary choice in reward processing is contingent upon contextual valence.

How choice influences risk processing: An ERP study.

The current study examined how the experience of choice by which individuals exercise control modulates risk processing during the anticipatory phase as indexed by the stimulus-preceding negativity (SPN), and the consummatory phase as indexed by the feedback-related negativity (FRN) and feedback P3 (fb-P3). Twenty-four participants performed a simple gambling task during which they could win or lose either a small (a low-risk condition) or a large (a high-risk condition) amount of points by either choosing freely between two doors (a choice condition) or accepting a computer-selected door (a no-choice condition) while their EEG was recorded. As expected, participants rated the high-risk condition as more risky than the low-risk condition and reported higher feelings of control for the choice versus no-choice condition. Regardless of the involvement of choice, risk processing in this task was associated with greater fb-P3 amplitudes. However, during the choice condition, risk processing was associated with a more negative SPN during the anticipatory phase and a more positive FRN during the consummatory phase, which was absent (the SPN) or reduced (the FRN) in the no-choice condition. These findings suggest that the modulation of risk processing by choice occurs during both the anticipatory phase and the consummatory phase, which may be driven by motivation salience imposed by control.

Monetary Incentives Modulate Feedback-related Brain Activity.

Previous research has shown that feedback evaluation is sensitive to monetary incentive. We investigated whether this sensitivity is driven by motivational salience (the difference between both rewarding and punishing events versus neutral events) or by motivational valence (the difference between rewarding and punishing events). Fifty-seven participants performed a monetary incentive delay task under a gain context, a loss context, and a neutral context with their electroencephalogram recorded. During the time domain, the feedback-related negativity (FRN) showed a motivational salience effect whereas the P3 displayed a reward valence effect. During the time-frequency domain, we observed a motivational salience effect for phase-locked theta power regardless of performance feedback, but a reward valence effect for non-phase-locked theta power in response to unsuccessful feedback. Moreover, we found a reward valence effect for phase-locked delta. These findings thus suggest that the affective modulation on feedback evaluation can be driven either by motivational valence or by motivational salience, which depends on the temporal dynamics (the FRN vs. the P3), the frequency dynamics (theta vs. delta power), as well as the phase dynamics (evoked vs. induced power).

Diminished choice effect on anticipating improbable rewards.

Previous research found that the neural substrates underlying perceived control highly overlap those of reward system, especially during reward anticipation stage. The current event-related potential study examined whether the experience of choice by which individuals exercise control is modulated by reward probability during reward anticipation stage as indexed by the stimulus-preceding negativity (SPN). Thirty participants performed a cued gambling task during which choices could be made either by themselves (a choice condition) or by a computer (a no-choice condition) with three levels of reward probability (low, medium, and high) while their EEG was recording. As expected, the participants perceived higher control during the choice compared to no-choice condition. Correspondingly, the SPN was enhanced in the choice condition than the no-choice condition. Critically, the SPN choice effect was present when reward probability was high and medium, but was diminished when reward probability was low. These findings suggest that the perceived control as exercised by choice is associated with reward anticipation, which may be sensitive to the fundamental properties of reward.

Nicotinic acid impairs assembly of leading edge in glioma cells.

Malignant glioma is a clinically formidable disease. It commonly leads to death within 5 years after diagnosis. Physicians are often baffled since the inevitable diffuse invasion deteriorates clinical outcomes rapidly. Therefore, cancerous infiltration presents a foremost challenge to all therapeutic strategies on glioblastoma multiforme (GBM). Previously, we demonstrated that nicotinic acid (NA) possesses a brand new function by targeting F-actin stress fibers. By treating HEK293 or NIH3T3 cells with a certain concentration of NA, the F-actin stress fiber was significantly disassembled. This notable finding inspired us to explore NA further in cancer cell lines, such as GBM cells, since F-actin stress fibers are the critical foundation of cell migration, proliferation and numerous essential signaling pathways. Expectedly, we observed that optimized concentrations of NA, 3.5 mM and 7.0 mM, detached U251 from culturing petri dishes. Moreover, 7.0 mM of NA was capable of disrupting the leading-edge assembly. Additionally, we collected paraffin specimens from 85 GBM patients and evaluated the expression pattern of paxillin. Notably, we found that discernable paxillin signals were detected in 67 out of 85 samples. Given that leading edge is critical for cancer cell migration, we propose that NA treatment may be developed into a potential therapy for malignant glioma.

Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation.

Malignant glioma is a formidable disease that commonly leads to death, mainly due to the invasion of tumor cells into neighboring tissues. Therefore, inhibition of tumor cell invasion may provide an effective therapy for malignant glioma. Here we report that nicotinic acid (NA), an essential vitamin, inhibits glioma cell invasion in vitro and in vivo. Treatment of the U251 glioma cells with NA in vitro results in reduced invasion, which is accompanied by a loss of mesenchymal phenotype and an increase in cell-cell adhesion. At the molecular level, transcription of the adherens junction protein E-cadherin is upregulated, leading to accumulation of E-cadherin protein at the cell-cell boundary. This can be attributed to NA's ability to facilitate the ubiquitination and degradation of Snail1, a transcription factor that represses E-cadherin expression. Similarly, NA transiently inhibits neural crest migration in Xenopus embryos in a Snail1-dependent manner, indicating that the mechanism of action for NA in cell migration is evolutionarily conserved. We further show that NA injection blocks the infiltration of tumor cells into the adjacent brain tissues and improves animal survival in a rat model of glioma. These results suggest that NA treatment may be developed into a potential therapy for malignant glioma.