Functional connectivity with ventromedial prefrontal cortex reflects subjective value for social rewards.

Previous studies showed alterations of brain function in the ventromedial prefrontal cortex of schizophrenia patients. Also, neurochemical changes, especially GABA level alteration, have been found in the medial prefrontal cortex of schizophrenia patients. However, the relationship between GABA level in the ventromedial prefrontal cortex and brain functional activity in schizophrenia patients remains unexplored. In total, 23 drug-naïve, first-episode psychosis patients and 26 matched healthy controls completed the study. The single voxel proton magnetic resonance spectroscopy data were acquired in ventromedial prefrontal cortex region, which was used as the seed region for resting-state functional connectivity analysis. The proton magnetic resonance spectroscopy data were processed to quantify the concentrations of GABA+, glutamine and glutamate, and N-acetylaspartate in ventromedial prefrontal cortex. Spearman correlation analysis was used to examine the relationship between metabolite concentration, functional connectivity and clinical variables. Pearson correlation analysis was used to examine the relationship between GABA+ concentration and functional connectivity value. In first-episode psychosis patients, GABA+ level in ventromedial prefrontal cortex was higher and was positively correlated with ventromedial prefrontal cortex-left middle orbital frontal cortex functional connectivity. N-acetylaspartate level was positively correlated with positive symptoms, and the functional connectivity between ventromedial prefrontal cortex and left precuneus was negatively associated with negative symptoms of first-episode psychosis patients. Our results indicated that ventromedial prefrontal cortex functional connectivity changes were positively correlated with higher local GABA+ level in first-episode psychosis patients. The altered neurochemical concentration and functional connectivity provide insights into the pathology of schizophrenia.

To explore the functions of temporal parietal junction (TPJ) as parts of attention networks in the pathogenesis of online game addiction using resting-state functional magnetic resonance imaging (fMRI). A total of 17 online game addicts (OGA) were recruited as OGA group and 17 healthy controls during the same period were recruited as CON group. The neuropsychological tests were performed for all of them to compare the inter-group differences in the results of Internet Addiction Test (IAT) and attention functions. All fMRI data were preprocessed after resting-state fMRI scanning. Then left and right TPJ were selected as regions of interest (ROIs) to calculate the linear correlation between TPJ and entire brain to compare the inter-group differences. Obvious differences existed between OGA group (71 ± 5 scores) and CON group (19 ± 7 scores) in the IAT results and attention function (P < 0.05). Compared with the controls, right TPJ in online game addicts showed decreased functional connectivity with bilateral ventromedial prefrontal cortex (VMPFC), bilateral hippocampal gyrus and bilateral amygdaloid nucleus, but increased functional connectivity with right cuneus.However, left TPJ demonstrated decreased functional connectivity with bilateral superior frontal gyrus and bilateral middle frontal gyrus, but increased functional connectivity with bilateral cuneus (P < 0.05). Altered functional connectivity of TPJ reflected its dysfunction in online game addicts.It suggests that TPJ is an important component of attention networks participating in the generation of online game addiction.

GENERAL COMMENTARY article Front. Hum. Neurosci., 07 November 2013Sec. Brain Health and Clinical Neuroscience Volume 7 - 2013 | https://doi.org/10.3389/fnhum.2013.00747

The neural mechanisms and durability of Δ9-tetrahydrocannabinol (THC) impact on threat processing in humans are not fully understood. Herein, we used functional MRI and psychophysiological tools to examine the influence of THC on the mechanisms of conditioned threat extinction learning, and the effects of THC on extinction memory retention when assessed 1 day and 1 week from learning. Healthy participants underwent threat conditioning on day 1. On day 2, participants were randomized to take one pill of THC or placebo (PBO) 2-h before threat extinction learning. Extinction memory retention was assessed 1 day and 1 week after extinction learning. We found that THC administration increased amygdala and ventromedial prefrontal cortex (vmPFC) activation during early extinction learning with no significant impact on skin conductance responses (SCR). When extinction memory retention was tested 24 h after learning, the THC group exhibited lower SCRs to the extinguished cue with no significant extinction-induced activations within the extinction network. When extinction memory retention was tested 1 week after learning, the THC group exhibited significantly decreased responses to the extinguished cues within the vmPFC and amygdala, but significantly increased functional coupling between the vmPFC, hippocampus, and dorsal anterior cingulate cortex during this extinction retention test. Our results are the first to report a long-term impact of one dose of THC on the functional activation of the threat extinction network and unveil a significant change in functional connectivity emerging after a week from engagement. We highlight the need for further investigating the long-term impact of THC on threat and anxiety circuitry.

Background: Impaired insight is a common feature in psychosis and an important predictor of variables such as functional outcome, prognosis, and treatment adherence. A cognitive process that may underlie insight in psychosis is self-reflection, or the conscious evaluation of one’s traits and characteristics. The current study aims to investigate the neural correlates of self-reflective processing and its relationship with insight in schizophrenia. Methods: Forty-seven schizophrenia patients and 21 healthy controls performed a self-reflection task in a functional magnetic resonance imaging (fMRI) scanner. The tasks comprised a self-reflection, close other-reflection, and a semantic (baseline) condition. Insight scores were obtained with the Schedule of Assessment of Insight Expanded. In addition, cognitive insight scores were obtained (Beck Cognitive Insight Scale [BCIS]). Results: Schizophrenia patients demonstrated less activation in the posterior cingulate cortex in the self- and other-reflection conditions and less activation in the precuneus in the other-reflection condition compared with healthy controls. Better insight was associated with greater response in the inferior frontal gyrus, anterior insula, and inferior parietal lobule during self-reflection. In addition, better cognitive insight was associated with higher activation in ventromedial prefrontal cortex during self-reflection. Conclusion: In the current study, evidence for a relationship between self-reflection and insight in patients with schizophrenia was found in brain areas related to self-reflection, self/other distinction and source attribution. The findings support the rationale for a treatment that is currently under evaluation, which attempts to increase insight by enhancing self-reflection.

Multiple types of reward, such as money, food or social approval, are capable of driving behavior. However, most previous investigations have only focused on one of these reward classes in isolation, as such it is not clear whether different reward classes have a unique influence on instrumental responding or whether the subjective value of the reward, rather than the reward type per se, is most important in driving behavior. Here, we investigate behavior using a well-established reward paradigm, Pavlovian-to-instrumental transfer (PIT), and three different reward types: monetary, food and social rewards. The subjective value of each reward type was matched using a modified Becker-DeGroot-Marschak (BDM) auction where subjective reward value was expressed through physical effort using a bimanual grip force task. We measured the influence of reward-associated stimuli on how participants distributed forces between hands when reaching a target effort range on the screen bimanually and on how much time participants spent in this target range. Participants spent significantly more time in the target range (15% ± 2% maximal voluntary contraction) when a stimulus was presented that was associated with a reward used during instrumental conditioning or Pavlovian conditioning compared to a stimulus associated with a neutral outcome (i.e., general PIT). The strength of the PIT effect was modulated by subjective value (i.e., individuals who showed a stronger PIT effect rated the value of rewards more highly), but not by reward type, demonstrating that stimuli of all reward types were able to act as appetitive reinforcers and influenced instrumental responding, when matched to the same subjective reward value. This is the first demonstration that individually matched monetary, food and social rewards are equally effective as appetitive reinforcers in PIT. These findings strengthen the hypotheses that the subjective value is crucial for how much reward-associated stimuli influence behavior.

Rationale Despite the critical role of choice processes in substance use disorders, the neurobehavioral mechanisms guiding human decisions about drugs remain poorly understood.ObjectivesWe aimed to characterize the neural encoding of subjective value (SV) for cannabis versus non-drug rewards (snacks) in people who use cannabis on a near-daily/daily frequency (PWUCF) and assessed the impact of cannabis and snack stimuli (‘cues’) on SV encoding.MethodsTwenty-one non-treatment-seeking PWUCF (≥4 days/week; 1 female) participated in an inpatient, crossover experiment with four counterbalanced conditions: 1. neutral cues/cannabis choices; 2. cannabis cues/cannabis choices; 3. neutral cues/snack choices; and 4. snack cues/snack choices. In each condition, participants were exposed to cues before an fMRI scan during which they repeatedly chose between 0-6 cannabis puffs/snacks and a set monetary amount, with randomly-selected choices implemented. The SV signal was operationalized as the neural correlates of the strength of preference for cannabis/snack choices. fMRI data were analyzed for twenty participants.ResultsDespite equivalent choice behavior, SV signals for cannabis, but not snacks, were observed in regions known to encode SV for various rewards (ventromedial prefrontal cortex, vmPFC; ventral striatum; dorsal posterior cingulate cortex, dPCC). SV encoding in vmPFC was stronger for cannabis than snacks. In the dPCC, the impact of cues on SV signals was moderated by reward type.ConclusionsPWUCF had expected neural value encoding for cannabis but disrupted non-drug SV encoding, despite equivalent choice behavior. This provides tentative support for theories that highlight dysregulated neural valuation of non-drug rewards as a hallmark of problematic cannabis use.

The neurobiological mechanisms that underlie the resistance of drug cue associations to extinction in addiction remain unknown. Fear extinction critically depends on the ventromedial prefrontal cortex (VMPFC). Here, we tested if this same region plays a role in extinction of non-fear, drug and pleasant cue associations. Eighteen chronic cocaine users and 15 matched controls completed three functional MRI scans. Participants first learned to associate an abstract cue (the conditioned stimulus, CS) with a drug-related (CSD+ ) or pleasant (CSP+ ) image. Extinction immediately followed where each CS was repeatedly presented without the corresponding image. Participants underwent a second identical session 24hours later to assess retention of extinction learning. Results showed that like fear extinction, non-fear-based extinction relies on the VMPFC. However, extinction-related changes in the VMPFC differed by cue valence and diagnosis. In controls, VMPFC activation to the CSD+ (which was unpleasant for participants) gradually increased as in fear extinction, while it decreased to the CSP+ , consistent with a more general role of the VMPFC in flexible value updating. Supporting a specific role in extinction retention, we further observed a cross-day association between VMPFC activation and skin conductance, a classic index of conditioned responses. Finally, cocaine users showed VMPFC abnormalities for both CSs, which, in the case of the CSD+ , correlated with craving. These data suggest a global deficit in extinction learning in this group that may hinder extinction-based treatment efforts. More broadly, these data show that the VMPFC, when functionally intact, supports extinction learning in diverse contexts in humans.

Stigmatization in society carries a high risk for development of psychopathology. Transgender persons are at particularly high risk for such stigmatization and social rejection by others. However, the neural correlates of ostracism in this group have not been captured. Twenty transgender men (TM, female-to-male) and 19 transgender women (TW, male-to-female) already living in their gender identity and 20 cisgender men (CM) and 20 cisgender women (CW) completed a cyberball task assessing both exclusion and re-inclusion during functional magnetic resonance imaging (fMRI). During psychosocial stress between-group differences were found in the dorsal and ventral anterior cingulate cortex (ACC) and the inferior frontal gyrus (IFG). Patterns were consistent with sex assigned at birth, i.e. CW showed greater activation in dorsal ACC and IFG relative to CM and TW. During re-inclusion, transgender persons showed greater ventral ACC activity relative to CW, possibly indicating persistent feelings of exclusion. Functional connectivity analyses supported these findings but showed a particularly altered functional connectivity between ACC and lateral prefrontal cortex in TM, which may suggest reduced emotional regulation to the ostracism experience in this group. Depressive symptoms or hormonal levels were not associated with these findings. The results bear implications for the role of social exclusion in development of mental health problems in socially marginalized groups.

Joyful growth vs. compulsive hedonism: A meta-analysis of brain activation on romantic love and addictive disorders

It is believed that choice behavior reveals the underlying value of goods. The subjective values of stimuli can be changed through reward-based learning mechanisms as well as by modifying the description of the decision problem, but it has yet to be shown that preferences can be manipulated by perturbing intrinsic values of individual items. Here we show that the value of food items can be modulated by the concurrent presentation of an irrelevant auditory cue to which subjects must make a simple motor response (i.e. cue-approach training). Follow-up tests show that the effects of this pairing on choice lasted at least two months after prolonged training. Eye-tracking during choice confirmed that cue-approach training increased attention to the cued items. Neuroimaging revealed the neural signature of a value change in the form of amplified preference-related activity in ventromedial prefrontal cortex.

Although it is well established that the ventromedial prefrontal cortex (vmPFC) represents value using a common currency across categories of rewards, it is unknown whether the vmPFC represents value irrespective of the sensory modality in which alternatives are presented. In the current study, male and female human subjects completed a decision-making task while their neural activity was recorded using functional magnetic resonance imaging. On each trial, subjects chose between a safe alternative and a lottery, which was presented visually or aurally. A univariate conjunction analysis revealed that the anterior portion of the vmPFC tracks subjective value (SV) irrespective of the sensory modality. Using a novel cross-modality multivariate classifier, we were able to decode auditory value based on visual trials and vice versa. In addition, we found that the visual and auditory sensory cortices, which were identified using functional localizers, are also sensitive to the value of stimuli, albeit in a modality-specific manner. Whereas both primary and higher-order auditory cortices represented auditory SV (aSV), only a higher-order visual area represented visual SV (vSV). These findings expand our understanding of the common currency network of the brain and shed a new light on the interplay between sensory and value information processing.

Activity in the dorsal anterior cingulate cortex (dACC) is observed across a variety of contexts, and its function remains intensely debated in the field of cognitive neuroscience. While traditional views emphasize its role in inhibitory control (suppressing prepotent, incorrect actions), recent proposals suggest a more active role in motivated control (invigorating actions to obtain rewards). Lagging behind empirical findings, formal models of dACC function primarily focus on inhibitory control, highlighting surprise, choice difficulty and value of control as key computations. Although successful in explaining dACC involvement in inhibitory control, it remains unclear whether these mechanisms generalize to motivated control. In this study, we derive predictions from three prominent accounts of dACC and test these with functional magnetic resonance imaging during value-based decision-making under time pressure. We find that the single mechanism of surprise best accounts for activity in dACC during a task requiring response invigoration, suggesting surprise signalling as a shared driver of inhibitory and motivated control.

Social networks shape our decisions by constraining what information we learn and from whom. Yet, the mechanisms by which network structures affect individual learning and decision-making remain unclear. Here, by combining a real-time distributed learning task with functional magnetic resonance imaging, computational modeling and social network analysis, we studied how humans learn from observing others' decisions on seven-node networks with varying topological structures. We show that learning on social networks can be approximated by a well-established error-driven process for observational learning, supported by an action prediction error encoded in the lateral prefrontal cortex. Importantly, learning is flexibly weighted toward well-connected neighbors, according to activity in the dorsal anterior cingulate cortex, but only insofar as social observations contain secondhand, potentially intertwining, information. These data suggest a neurocomputational mechanism of network-based filtering on the sources of information, which may give rise to biased learning and the spread of misinformation in an interconnected society.

Brain activation to task-irrelevant disorder-related threat in social anxiety disorder: The impact of symptom severity