Dorsolateral and ventromedial prefrontal cortex orchestrate normative choice.

Humans are noted for their capacity to over-ride self-interest in favor of normatively valued goals. We examined the neural circuitry that is causally involved in normative, fairness-related decisions by generating a temporarily diminished capacity for costly normative behavior, a 'deviant' case, through non-invasive brain stimulation (repetitive transcranial magnetic stimulation) and compared normal subjects' functional magnetic resonance imaging signals with those of the deviant subjects. When fairness and economic self-interest were in conflict, normal subjects (who make costly normative decisions at a much higher frequency) displayed significantly higher activity in, and connectivity between, the right dorsolateral prefrontal cortex (DLPFC) and the posterior ventromedial prefrontal cortex (pVMPFC). In contrast, when there was no conflict between fairness and economic self-interest, both types of subjects displayed identical neural patterns and behaved identically. These findings suggest that a parsimonious prefrontal network, the activation of right DLPFC and pVMPFC, and the connectivity between them, facilitates subjects' willingness to incur the cost of normative decisions.

Virtual reality and the role of the prefrontal cortex in adults and children

In this review, the neural underpinnings of the experience of presence are outlined. Firstly, it is shown that presence is associated with activation of a distributed network, which includes the dorsal and ventral visual stream, the parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and the thalamus. Secondly, the dorsolateral prefrontal cortex (DLPFC) is identified as a key node of the network as it modulates the activity of the network and the associated experience of presence. Thirdly, children lack the strong modulatory influence of the DLPFC on the network due to their unmatured frontal cortex. Fourthly, it is shown that presence-related measures are influenced by manipulating the activation in the DLPFC using transcranial direct current stimulation (tDCS) while participants are exposed to the virtual roller coaster ride. Finally, the findings are discussed in the context of current models explaining the experience of presence, the rubber hand illusion, and out-of-body experiences.

The Role of the Right Posterior Parietal Cortex in Letter Migration between Words

When briefly presented with pairs of words, skilled readers can sometimes report words with migrated letters (e.g., they report hunt when presented with the words hint and hurt). These letter migration phenomena have been often used to investigate factors that influence reading such as letter position coding. However, the neural basis of letter migration is poorly understood. Previous evidence has implicated the right posterior parietal cortex (PPC) in processing visuospatial attributes and lexical properties during word reading. The aim of this study was to assess this putative role by combining an inhibitory TMS protocol with a letter migration paradigm, which was designed to examine the contributions of visuospatial attributes and lexical factors. Temporary interference with the right PPC led to three specific effects on letter migration. First, the number of letter migrations was significantly increased only in the group with active stimulation (vs. a sham stimulation group or a control group without stimulation), and there was no significant effect on other error types. Second, this effect occurred only when letter migration could result in a meaningful word (migration vs. control context). Third, the effect of active stimulation on the number of letter migrations was lateralized to target words presented on the left. Our study thus demonstrates that the right PPC plays a specific and causal role in the phenomenon of letter migration. The nature of this role cannot be explained solely in terms of visuospatial attention, rather it involves an interplay between visuospatial attentional and word reading-specific factors.

Tonic activity level in the right prefrontal cortex predicts individuals' risk taking

Human risk taking is characterized by a large amount of individual heterogeneity. In this study, we applied resting-state electroencephalography, which captures stable individual differences in neural activity, before subjects performed a risk-taking task. Using a source-localization technique, we found that the baseline cortical activity in the right prefrontal cortex predicts individual risk-taking behavior. Individuals with higher baseline cortical activity in this brain area display more risk aversion than do other individuals. This finding demonstrates that neural characteristics that are stable over time can predict a highly complex behavior such as risk-taking behavior and furthermore suggests that hypoactivity in the right prefrontal cortex might serve as a dispositional indicator of lower regulatory abilities, which is expressed in greater risk-taking behavior.

Disruption of right prefrontal cortex by low-frequency repetitive transcranial magnetic stimulation induces risk-taking behavior

Decisions require careful weighing of the risks and benefits associated with a choice. Some people need to be offered large rewards to balance even minimal risks, whereas others take great risks in the hope for an only minimal benefit. We show here that risk-taking is a modifiable behavior that depends on right hemisphere prefrontal activity. We used low-frequency, repetitive transcranial magnetic stimulation to transiently disrupt left or right dorsolateral prefrontal cortex (DLPFC) function before applying a well known gambling paradigm that provides a measure of decision-making under risk. Individuals displayed significantly riskier decision-making after disruption of the right, but not the left, DLPFC. Our findings suggest that the right DLPFC plays a crucial role in the suppression of superficially seductive options. This confirms the asymmetric role of the prefrontal cortex in decision-making and reveals that this fundamental human capacity can be manipulated in normal subjects through cortical stimulation. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse or pathological gambling.

Lateral prefrontal cortex and self-control in intertemporal choice.

Disruption of function of left, but not right, lateral prefrontal cortex (LPFC) with low-frequency repetitive transcranial magnetic stimulation (rTMS) increased choices of immediate rewards over larger delayed rewards. rTMS did not change choices involving only delayed rewards or valuation judgments of immediate and delayed rewards, providing causal evidence for a neural lateral-prefrontal cortex-based self-control mechanism in intertemporal choice.

Disrupting the prefrontal cortex diminishes the human ability to build a good reputation.

Reputation formation pervades human social life. In fact, many people go to great lengths to acquire a good reputation, even though building a good reputation is costly in many cases. Little is known about the neural underpinnings of this important social mechanism, however. In the present study, we show that disruption of the right, but not the left, lateral prefrontal cortex (PFC) with low-frequency repetitive transcranial magnetic stimulation (rTMS) diminishes subjects' ability to build a favorable reputation. This effect occurs even though subjects' ability to behave altruistically in the absence of reputation incentives remains intact, and even though they are still able to recognize both the fairness standards necessary for acquiring and the future benefits of a good reputation. Thus, subjects with a disrupted right lateral PFC no longer seem to be able to resist the temptation to defect, even though they know that this has detrimental effects on their future reputation. This suggests an important dissociation between the knowledge about one's own best interests and the ability to act accordingly in social contexts. These results link findings on the neural underpinnings of self-control and temptation with the study of human social behavior, and they may help explain why reputation formation remains less prominent in most other species with less developed prefrontal cortices.

Diminishing risk-taking behavior by modulating activity in the prefrontal cortex: a direct current stimulation study.

Studies have shown increased risk taking in healthy individuals after low-frequency repetitive transcranial magnetic stimulation, known to transiently suppress cortical excitability, over the right dorsolateral prefrontal cortex (DLPFC). It appears, therefore, plausible that differential modulation of DLPFC activity, increasing the right while decreasing the left, might lead to decreased risk taking, which could hold clinical relevance as excessively risky decision making is observed in clinical populations leading to deleterious consequences. The goal of the present study was to investigate whether risk-taking behaviors could be decreased using concurrent anodal transcranial direct current stimulation (tDCS) of the right DLPFC, which allows upregulation of brain activity, with cathodal tDCS of the left DLPCF, which downregulates activity. Thirty-six healthy volunteers performed the risk task while they received either anodal over the right with cathodal over the left DLPFC, anodal over the left with cathodal over the right DLPFC, or sham stimulation. We hypothesized that right anodal/left cathodal would decrease risk-taking behavior compared with left anodal/right cathodal or sham stimulation. As predicted, during right anodal/left cathodal stimulation over the DLPFC, participants chose more often the safe prospect compared with the other groups. Moreover, these participants appeared to be insensitive to the reward associated with the prospects. These findings support the notion that the interhemispheric balance of activity across the DLPFCs is critical in decision-making behaviors. Most importantly, the observed suppression of risky behaviors suggests that populations with boundless risk-taking behaviors leading to negative real-life consequences, such as individuals with addiction, might benefit from such neuromodulation-based approaches.

Resisting the power of temptations: the right prefrontal cortex and self-control.

Imagine you are overweight and you spot your favorite pastry in the storefront of a bakery. How do you manage to resist this temptation? Or to give other examples, how do you manage to restrain yourself from overspending or succumbing to sexual temptations? The present article summarizes two recent studies stressing the fundamental importance of inhibition in the process of decision making. Based on the results of these studies, we dare to claim that the capacity to resist temptation depends on the activity level of the right prefrontal cortex (PFC).

Diminishing reciprocal fairness by disrupting the right prefrontal cortex.

Humans restrain self-interest with moral and social values. They are the only species known to exhibit reciprocal fairness, which implies the punishment of other individuals' unfair behaviors, even if it hurts the punisher's economic self-interest. Reciprocal fairness has been demonstrated in the Ultimatum Game, where players often reject their bargaining partner's unfair offers. Despite progress in recent years, however, little is known about how the human brain limits the impact of selfish motives and implements fair behavior. Here we show that disruption of the right, but not the left, dorsolateral prefrontal cortex (DLPFC) by low-frequency repetitive transcranial magnetic stimulation substantially reduces subjects' willingness to reject their partners' intentionally unfair offers, which suggests that subjects are less able to resist the economic temptation to accept these offers. Importantly, however, subjects still judge such offers as very unfair, which indicates that the right DLPFC plays a key role in the implementation of fairness-related behaviors.

The association between implicit alcohol attitudes and drinking behavior is moderated by baseline activation in the lateral prefrontal cortex

OBJECTIVE Intense alcohol consumption is a risk factor for a number of health problems. Dual-process models assume that self-regulatory behavior such as drinking alcohol is guided by both reflective and impulsive processes. Evidence suggests that (a) impulsive processes such as implicit attitudes are more strongly associated with behavior when executive functioning abilities are low, and (b) higher neural baseline activation in the lateral prefrontal cortex (PFC) is associated with better inhibitory control. The present study integrates these 2 strands of research to investigate how individual differences in neural baseline activation in the lateral PFC moderate the association between implicit alcohol attitudes and drinking behavior. METHOD Baseline cortical activation was measured with resting electroencephalography (EEG) in 89 moderate drinkers. In a subsequent behavioral testing session they completed measures of implicit alcohol attitudes and self-reported drinking behavior. RESULTS Implicit alcohol attitudes were related to self-reported alcohol consumption. Most centrally, implicit alcohol attitudes were more strongly associated with drinking behavior in individuals with low as compared with high baseline activation in the right lateral PFC. CONCLUSIONS These findings are in line with predictions made on the basis of dual-process models. They provide further evidence that individual differences in neural baseline activation in the right lateral PFC may contribute to executive functioning abilities such as inhibitory control. Moreover, individuals with strongly positive implicit alcohol attitudes coupled with a low baseline activation in the right lateral PFC may be at greater risk of developing unhealthy drinking patterns than others.

Interactions between dorsolateral and ventromedial prefrontal cortex underlie context-dependent stimulus valuation in goal-directed choice.

External circumstances and internal bodily states often change and require organisms to flexibly adapt valuation processes to select the optimal action in a given context. Here, we investigate the neurobiology of context-dependent valuation in 22 human subjects using functional magnetic resonance imaging. Subjects made binary choices between visual stimuli with three attributes (shape, color, and pattern) that were associated with monetary values. Context changes required subjects to deviate from the default shape valuation and to integrate a second attribute in order to comply with the goal to maximize rewards. Critically, this binary choice task did not involve any conflict between opposing monetary, temporal, or social preferences. We tested the hypothesis that interactions between regions of dorsolateral and ventromedial prefrontal cortex (dlPFC; vmPFC) implicated in self-control choices would also underlie the more general function of context-dependent valuation. Consistent with this idea, we found that the degree to which stimulus attributes were reflected in vmPFC activity varied as a function of context. In addition, activity in dlPFC increased when context changes required a reweighting of stimulus attribute values. Moreover, the strength of the functional connectivity between dlPFC and vmPFC was associated with the degree of context-specific attribute valuation in vmPFC at the time of choice. Our findings suggest that functional interactions between dlPFC and vmPFC are a key aspect of context-dependent valuation and that the role of this network during choices that require self-control to adjudicate between competing outcome preferences is a specific application of this more general neural mechanism.

Prefrontal Thinning Affects Functional Connectivity and Regional Homogeneity of the Anterior Cingulate Cortex in Depression

Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment.

CHOLINERGIC MODULATION OF THALAMIC INPUT INTO THE CINGULATE CORTEX

This research demonstrates cholinergic modulation of thalamic input into the limbic cortex. A projection from the mediodorsal thalamus (MD) to the anterior cingulate cortex was defined anatomically and physiologically. Injections of horse-radish peroxidase into the anterior cingulate cortex labels neurons in the lateral, parvocellular, region of MD. Electrical Stimulation of this area produces a complex field potential in the anterior cingulate cortex which was further characterized by current density analysis and single cell recordings.^ The monsynaptic component of the response was identified as a large negative field which is maximal in layer IV of the anterior cingulate cortex. This response shows remarkable tetanic potentiation of frequencies near 7 Hz. During a train of 50 or more stimuli, the response would grow quickly and remain at a fairly stable potentiated level throughout the train.^ Cholinergic modulation of this thalamic response was demonstrated by iontophoretic application of the cholinergic agonist carbachol decreased the effectiveness of the thalamic imput by rapidly attenuation the response during a train of stimuli. The effect was apparently mediated by muscarinic receptors since the effect of carbachol was blocked by atropine but not by hexamethonium.^ To determine the source of the cingulate cortex cholinergic innervation, lesions were made in the anterior and medial thalamus and in the nucleus of the diagonal band of Broca. The effects of these lesions on choline acetyltranferase activity in the cingulate cortex were determined by a micro-radio-enzymatical assay. Only the lesions of the nucleus of the diagonal band significantly decreased the choline acetyltransferase activity in the cingulate cortex regions. Therefore, the diagonal band appears to be a major source of sensory cholinergic innervation and may be involved in gating of sensory information from the thalamus into the limbic cortex. Attempts to modulate the cingulate response to MD stimulation with electrical stimulation of the diagonal band, however were not successful.^

The contributions of the amygdala, orbital frontal cortex and hippocampal formation to primate social cognition

Deficits in social cognition are prominent symptoms of many human psychiatric disorders, but the origin of such deficits remains largely unknown. To further current knowledge regarding the neural network mediating social cognition, the present research program investigated the individual contributions of two temporal lobe structures, the amygdala and hippocampal formation, and one frontal lobe region, the orbital frontal cortex (Areas 11 and 13), to primate social cognition. Based on previous research, we hypothesized that the amygdala, hippocampal formation and orbital frontal cortex contribute significantly to the formation of new social relationships, but less to the maintenance of familiar ones. ^ Thirty-six male rhesus macaques (Macaca mulatta) served as subjects, and were divided into four experimental groups: Neurotoxic amygdala lesion (A-ibo, n = 9), neurotoxic or aspiration orbital frontal cortex lesion (O, n = 9), neurotoxic hippocampal formation lesion (H-ibo, n = 9) or sham-operated control (C, n = 9). Six social groups (tetrads) were created, each containing one member from each experimental group. The effect of lesion on established social relationships was assessed during pre- and post-surgical unrestrained social interactions, whereas the effect of lesion on the formation of new relationships was assessed during an additional phase of post-surgical testing with shuffled tetrad membership. Results indicated that these three neural structures each contribute significantly to both the formation and maintenance of social relationships. Furthermore, the amygdala appears to primarily mediate normal responses to threatening social signals, whereas the orbital frontal cortex plays a more global role in social cognition by mediating responses to both threatening and affiliative social signals. By contrast, the hippocampal formation seems to contribute to social cognition indirectly by providing access to previous experience during social judgments. ^ These conclusions were further investigated with three experiments that measured behavioral and physiological (stress hormone) reactivity to threatening stimuli, and three additional experiments that measured subjects' ability to flexibly alter behavioral responses depending on the incentive value of a food reinforcer. Data from these six experiments further confirmed and strengthened the three conclusions originating from the social behavior experiments and, when combined with the current literature, helped to formulate a simple, but testable, theoretical model of primate social cognition. ^