Activation In Lateral Orbitofrontal Cortex Research Articles

Value Representations of Spite Sensitivity in Psychosis on the Minnesota Trust Game

BackgroundSpite sensitivity provides a valuable construct to understand persecutory ideation and its underlying neural mechanisms. We examined the relationship between persecution and spite sensitivity in psychosis to identify their neural substrates. MethodsIn a 3T magnetic resonance imaging scanner, 49 participants with psychosis played the Minnesota Trust Game, in which they decided whether to take a small amount of money or trust a partner to choose between fair and unfair distributions of money. In some conditions, the partner benefited from the unfair option, while in others, the partner lost money. Participants who were untrusting in the second condition (suspiciousness) showed heightened sensitivity to spite. Behavioral measures included mistrust during the 2 conditions of the game, which were compared with Brief Psychiatric Rating Scale persecution and computational modeling. Functional connectivity and blood oxygen level–dependent analyses were also conducted on a priori regions during spite-sensitive decisions. ResultsBehavioral results replicated previous findings; participants who experienced more persecutory ideation trusted less, specifically in the suspiciousness condition. Functional connectivity findings showed that decreased connectivity between the orbitofrontal cortex–insula and the left frontoparietal network was associated with increased persecutory ideation and estimated spite-guilt (a marker of spite sensitivity). Additionally, we found differences between conditions in caudate nucleus, medial prefrontal cortex, and lateral orbitofrontal cortex activation. ConclusionsThese findings provide a new perspective on the origin of positive symptoms by identifying primary brain circuits that are related to both spite sensitivity and persecutory ideation.

Activity in the Dorsomedial Striatum Underlies Serial Reversal Learning Performance Under Probabilistic Uncertainty

BackgroundCorticostriatal circuits, particularly the dorsomedial striatum (DMS) and lateral orbitofrontal cortex, are critical for navigating reversal learning under probabilistic uncertainty. These same areas are implicated in the reversal learning impairments observed in individuals with psychosis as well as their psychotic symptoms, suggesting that they may share a common neurobiological substrate. To address this question, we used psychostimulant exposure and specific activation of the DMS during reversal learning in mice to assess corticostriatal activity. MethodsWe used amphetamine treatment to induce psychosis-relevant neurobiology in male mice during reversal learning and to examine pathway-specific corticostriatal activation. To determine the causal role of DMS activity, we used chemogenetics to drive midbrain inputs during a range of probabilistic contingencies. ResultsMice treated with amphetamine showed altered punishment learning, which was associated with decreased shifting after losses and increased perseverative errors after reversals. Reversal learning performance and strategies were dependent on increased activity in lateral orbitofrontal cortex to DMS circuits as well as in the DMS itself. Specific activation of midbrain to DMS circuits also decreased shifting after losses and reversal learning performance. However, these alterations were dependent on the probabilistic contingency. ConclusionsOur work suggests that the DMS plays a multifaceted role in reversal learning. Increasing DMS activity impairs multiple reversal learning processes dependent on the level of uncertainty, confirming its role in the maintenance and selection of incoming cortical inputs. Together, these outcomes suggest that elevated dopamine levels in the DMS could contribute to decision-making impairments in individuals with psychosis.

Analysis of lateral orbitofrontal cortex activation on acquisition of fear extinction and neuronal activities in fear circuit.

Inappropriate fear expression and failure of fear extinction are commonly seen in patients with post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). Among the patients, aberrant and asymmetric activation of the lateral orbitofrontal cortex (lOFC) is reported in some clinical cases. In this study, we aimed to examine the role of lOFC activation in extinction acquisition and explore the potential functional lateralization of lOFC on extinction. We bilaterally or unilaterally activated the lOFC with N-methyl-D-aspartate (NMDA) before fear extinction acquisition in rats. Our data suggested that both left and bilateral lOFC activation interfered with the in-session expression of conditioned fear, whereas activation of the right lOFC did not. In addition, pre-extinction unilateral or bilateral activation of the lOFC, regardless of the side, impaired the acquisition of fear extinction. We also quantified the neuronal activities during the late phase of extinction with immunohistochemical approach. Our data showed that activation of the lOFC increased the neuronal activities on the injection side(s) in the medial prefrontal cortex (mPFC), the lateral amygdala (LA), the basolateral amygdala (BLA; preferentially the non-GABAergic neurons), and the medial intercalated cells (mITC; preferentially the right side). To conclude, aberrant activation of the lOFC during extinction disturbed the excitatory/inhibitory balance of neuronal activities in fear-related brain regions, which interfered with the expression of conditioned fear and impaired the acquisition of fear extinction.

Enhanced Instructed Fear Learning in Delusion-Proneness.

Psychosis is associated with distorted perceptions and deficient bottom-up learning such as classical fear conditioning. This has been interpreted as reflecting imprecise priors in low-level predictive coding systems. Paradoxically, overly strong beliefs, such as overvalued beliefs and delusions, are also present in psychosis-associated states. In line with this, research has suggested that patients with psychosis and associated phenotypes rely more on high-order priors to interpret perceptual input. In this behavioural and fMRI study we studied two types of fear learning, i.e., instructed fear learning mediated by verbal suggestions about fear contingencies and classical fear conditioning mediated by low level associative learning, in delusion proneness—a trait in healthy individuals linked to psychotic disorders. Subjects were shown four faces out of which two were coupled with an aversive stimulation (CS+) while two were not (CS-) in a fear conditioning procedure. Before the conditioning, subjects were informed about the contingencies for two of the faces of each type, while no information was given for the two other faces. We could thereby study the effect of both classical fear conditioning and instructed fear learning. Our main outcome variable was evaluative rating of the faces. Simultaneously, fMRI-measurements were performed to study underlying mechanisms. We postulated that instructed fear learning, measured with evaluative ratings, is stronger in psychosis-related phenotypes, in contrast to classical fear conditioning that has repeatedly been shown to be weaker in these groups. In line with our hypothesis, we observed significantly larger instructed fear learning on a behavioural level in delusion-prone individuals (n = 20) compared to non-delusion-prone subjects (n = 23; n = 20 in fMRI study). Instructed fear learning was associated with a bilateral activation of lateral orbitofrontal cortex that did not differ significantly between groups. However, delusion-prone subjects showed a stronger functional connectivity between right lateral orbitofrontal cortex and regions processing fear and pain. Our results suggest that psychosis-related states are associated with a strong instructed fear learning in addition to previously reported weak classical fear conditioning. Given the similarity between nocebo paradigms and instructed fear learning, our results also have an impact on understanding why nocebo effects differ between individuals.

Medial or lateral orbitofrontal cortex activation during fear extinction differentially regulates fear renewal

Some anxiety-related disorders, such as panic disorder, specific phobia, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD), develop because of the poor regulation and inappropriate expression of fear-related behavior at the wrong place and wrong time. In clinical settings, exposure therapy, which consists of repeated presentation of trauma-related stimuli without real threats in the therapeutic context, is commonly used to treat these disorders. However, 30–50 % of patients suffer from the recurrence of anxiety symptoms after they leave the therapeutic context. This behavioral phenomenon is called renewal. In this study, ABA Pavlovian fear renewal paradigm was used to assess the role of the aberrant orbitofrontal cortex (OFC) activation, a symptom of OCD patients, on fear regulation in laboratory settings. The rats were fear conditioned in one context (context A), extinguished to the tones in another context (context B), and then tested in either context A or B. During extinction, rats were subjected to lateral or medial OFC activation. We found that rats that underwent extinction with either lateral or medial OFC activation were unable to use the context to determine whether it was a safe or dangerous context during renewal test. Interestingly, the rats with lateral OFC activation during extinction showed generally high fear, whereas the rats with medial OFC activation during extinction showed generally low fear. In conclusion, our results suggested that aberrant activation of specifically the lateral OFC may have a negative impact during exposure therapy treatments and results in their poor regulation of fear-related behavior.

In Search of the Most Reproducible Neural Vulnerability Factors that Predict Future Weight Gain: Analyses of Data from Six Prospective Studies.

We tested if we could replicate the main effect relations of elevated striatum and lateral orbitofrontal cortex (OFC) response to high-calorie food stimuli to weight gain reported in past papers in six prospective datasets that used similar fMRI paradigms. Participants in Study 1 (N = 37; M age = 15.5), Study 2 (N = 160; M age = 15.3), Study 3 (N = 130; M age = 15.0), Study 4 (N = 175; M age = 14.3), Study 5 (N = 45; M age = 20.8), and Study 6 (N = 49; M age = 31.1) completed fMRI scans at baseline and had their BMI and body fat (Studies 4 and 6 only) measured at baseline and over follow-ups. Elevated striatal response to palatable food images predicted BMI gain in Studies 1 and 6 and body fat gain in Study 6. Lateral OFC activation did not predict weight gain in any of the six studies. Results provide limited support for the hypothesis that elevated reward region responsivity to palatable food images predicts weight gain. Factors that make replication difficult are discussed and potential solutions considered.

Influence of Fluoxetine on Perseverative Behavior-Related Activity in Lateral Orbitofrontal Cortex

In patients with obsessive-compulsive disorder (OCD), abnormal orbitofrontal cortex (OFC) activity normalizes after fluoxetine treatment. However, little is known about how fluoxetine affects encoding of compulsive behaviors in OFC neurons. Using the Sapap3-KO mouse as a model for OCD-relevant perseverative behaviors, we measured self-grooming related neural activity with in vivo calcium imaging in lateral OFC (LOFC) before and after fluoxetine treatment.

Lateral Orbitofrontal Cortical Modulation on the Medial Prefrontal Cortex-Amygdala Pathway: Differential Regulation of Intra-Amygdala GABAA and GABAB Receptors.

Background:The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex and lateral orbitofrontal cortex. Earlier studies have shown that lateral orbitofrontal cortex activation exerts an inhibitory gating on medial prefrontal cortex-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process.Methods:In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to medial prefrontal cortex activation, tested lateral orbitofrontal cortex gating at different delays (lateral orbitofrontal cortex-medial prefrontal cortex delays: 25, 50, 100, 250, 500, and 1000 milliseconds), and examined differential contribution of GABAA and GABAB receptors with iontophoresis.Results:Relative to baseline, lateral orbitofrontal cortex stimulation exerted an inhibitory modulatory gating on the medial prefrontal cortex-amygdala pathway and was effective up to a long delay of 500 ms (long-delay latencies at 100, 250, and 500 milliseconds). Moreover, blockade of intra-amygdala GABAA receptors with bicuculline abolished the lateral orbitofrontal cortex inhibitory gating at both short- (25 milliseconds) and long-delay (100 milliseconds) intervals, while blockade of GABAB receptors with saclofen reversed the inhibitory gating at long delay (100 milliseconds) only. Among the majority of the neurons examined (8 of 9), inactivation of either GABAA or GABAB receptors during baseline did not change evoked probability per se, suggesting that local feed-forward inhibitory mechanism is pathway specific.Conclusions:Our results suggest that the effect of lateral orbitofrontal cortex inhibitory modulatory gating was effective up to 500 milliseconds and that intra-amygdala GABAA and GABAB receptors differentially modulate the short- and long-delay lateral orbitofrontal cortex inhibitory gating on the medial prefrontal cortex-amygdala pathway.

The influences of social value orientation on prosocial behaviors: The evidences from behavioral and neuroimaging studies

“Economic Man Assumption” proposed that humans are rational, whose only goal is to pursue their maximum self- interest. However, costly prosoial behaviors, such as helping, comforting, or donation, are commonly seen in daily life. Researchers put forward social value orientation (SVO) to explain why people exhibit such behaviors. SVO refers to a stable preference for outcomes for self versus others in interdependent situation, which further affects prosocial behaviors in social dilemmas. The commonly used measurements of SVO are the Triple-Dominance Scale and the Slider Measure. Based on these measures, SVO is classified into two categories: prosocial value orientation, and proself value orientation. The latter one is further subdivided to individualistic and competitive value orientations. People with prosocial orientation tend to maximize joint interest, people with individualistic orientation tend to maximize absolute outcome, while people with competitive orientation tend to maximize relative outcome. Previous studies have suggested that SVO can express automatically, and stably influence social behaviors. This article reviewed existing researches and mainly discusses its influence on trust behavior, cooperation and fair decisions in social contexts. A growing body of evidence suggests that prosocial individuals show more trust behaviors, cooperation, and fair decisions, which are further reflected on neural activities. Specifically, temporal-parietal junction (TPJ), insula and anterior cingulate cortex (ACC) show stronger activation when prosocials choose to cheat compared to be honest/trustworthy in trust game, while for proselfs there are no significant differences. In social dilemma games, prosocials show more cooperative behavior, accompanied by increased activation in lateral orbitofrontal cortex (OFC), anterior superior temporal sulcus (aSTS) and inferior parietal lobule, which brain regions are relevant to norm compliance, routine moral judgment, and social awareness. While for proselfs, increased activation is found in dorsolateral prefrontal cortex (DLPFC), which is relevant to calculation. Researches have also found prosocials make more rejection to unfair allocation, and the degree of inequity aversion in prosocials is predictable from amygdala activity. In light of existing literature, we summarized four aspects of how SVO affects prosocial behaviors. The first one is that prosocials have a stronger internal cooperation motivation relative to proselfs so that prosocial behaviors are processed automatically for prosocials. Second, prosocials have a higher expectation of others’ prosocial behaviors, this expectation in turn influences himself/herself’s behaviors. The third is that prosocial ones show more social responsibility in social interaction that they tend to maximize joint outcome. Last but not least, individuals with different SVOs show different social learning patterns which affects information collection and decision making during social interaction. Before the end, we propose several research directions. First is the differences in social learning patterns between individuals with different SVOs. Secondly, the interactive effects of SVO and other personality traits, such as empathy and trust, on prosocial behavior need to be investigated. More neural biochemical researches which focus on neurotransmitter as well as gene of different SVOs are also required. At last, in order to better apply research results to real life, ecological validity of research need to be improved.

Neural Mechanisms of Credit Assignment in a Multicue Environment.

Learners should infer which features of environments are predictive of significant events, such as rewards. This "credit assignment" problem is particularly challenging when any of several cues might be predictive. We show that human subjects solve the credit assignment problem by implicitly "hypothesizing" which cue is relevant for predicting subsequent outcomes, and then credit is assigned according to this hypothesis. This process is associated with a distinctive pattern of activity in a part of medial frontal cortex. By contrast, when unexpected outcomes occur, hypotheses are redirected toward alternative cues, and this process is associated with activity in lateral orbitofrontal cortex.

EPA-0436 – Orbitofrontal cortex as a brain biomarker of suicide vulnerability in mood disorders: role of valuation processes and serotonergic genes

The epidemiology of suicidal behaviours (SB) reflects our lack of understanding of these complex behaviours, as well as our difficulty to predict them. It is now admitted that vulnerability to SB relies on the interaction between genetic predisposition and environmental factors. Serotoninergic genes and orbitofrontal cortex (OFC) dysfunction are potential biomarkers for SB. Three groups of euthymic participants were included: 1) suicide attempters—individuals with a past history of both major depressive episode and suicidal behaviour; 2) affective comparison subjects—individuals with a past history of major depressive episode but no history of suicidal acts; 3) healthy comparison subjects—individuals with no past history of any DSM-IV axis I diagnosis. We compared neural activity using functional MRI while performing face processing (happiness, anger, sadness visualisation) and decision-making tasks (Iowa Gambling Task). We characterized of our sample for five genotypes: 5HTTLPR, TPH-1 rs1800532, TPH-1 rs7933505, MAOA u-VNTR, and TPH2 rs7305115. We performed a priori ROI analysis focused on OFC. We found decreased activation during risky vs. safe choices and increased activation during wins vs. losses in left OFC in suicide attempters in comparison to controls. Left lateral OFC activation was correlated with IGT net score in suicide attempters. We found an increased activation of right lateral OFC cortex in suicide attempters in comparison to affective controls when viewing angry but not happy or sad faces vs. neutral faces. Lateral OFC activation was modulated by 5HTTLPR polymorphisms. Based on OFC dysfunction, suicide attempters may overevaluate social negative signs and underevaluate deleterious consequences of short-term rewarded choices.

Neurocognitive Mechanisms of Impaired Decision Making in Pathological Gambling

Neurocognitive Mechanisms of Impaired Decision Making in Pathological Gambling

Neural Activation During Facial Emotion Processing in Unmedicated Bipolar Depression, Euthymia, and Mania

Studies incorporating direct comparisons across all phases of bipolar (BP) disorder are needed to elucidate the pathophysiology of bipolar disorder. However, functional neuroimaging studies that differentiate bipolar mood states from each other and from healthy subjects are few and have yielded inconsistent findings. One hundred five unmedicated adults were recruited: 30 with current bipolar depression (BPD), 30 with current bipolar hypomania or mania (BPM), 15 bipolar euthymic (BPE), and 30 healthy control subjects (HC). All subjects were diagnosed with DSM-IV BP (type I or II) using a structured clinical interview. Groups were age- and gender-ratio matched. In 3T functional magnetic resonance imaging experiments, subjects completed a negative facial emotion matching task. Bipolar euthymic and BPD groups exhibited increased amygdala activation compared with HCs in response to the negative faces; however, in the BPM group, this increase was not seen. Conversely, both BPE and BPM groups had increased activation in the insula relative to HCs, but in the BPD group, this effect was not seen. All three BP groups exhibited increased activation of the putamen compared with HCs. In the cortical areas, the BPM group exhibited decreased left lateral orbitofrontal cortex activation compared with both BPEs and HCs, increased dorsal anterior cingulate cortex activation compared with the BPD group, and increased dorsolateral prefrontal cortical activation compared with all other groups. Both state- and trait-related abnormalities in corticolimbic activation were seen in response to the negative facial emotion processing in a large sample of unmedicated adults across BP mood states.

Neural evidence for reduced apprehensiveness of familiarized stimuli in a mere exposure paradigm

Mere familiarization with a stimulus increases liking for it or similar stimuli (“mere exposure” effects) as well as perceptual fluency, indexed by the speed and accuracy of categorizing it or similar stimuli (“priming” effects). Candidate mechanisms proposed to explain mere exposure effects include both increased positive affect associated with greater perceptual fluency, and reduced negative affect associated with diminished apprehensiveness of novel stimuli. Although these two mechanisms are not mutually exclusive, it is difficult for behavioral measures to disentangle them, since increased liking or other indices of greater positive affect toward exposed stimuli could result from increases in positive feelings or decreases in negative feelings or both. The present study sought to clarify this issue by building on research showing a dissociation at the neural level in which the lateral orbitofrontal cortex (LOFC) is activated more by negatively valenced than by neutral or positively valenced stimuli, with the reverse effect for medial orbitofrontal cortex (MOFC). Supporting the reduced apprehensiveness hypothesis, we found lower LOFC activation to familiarized faces and objects (repetition suppression). We did not find evidence to support the positive affect hypothesis in increased activation to familiarized stimuli in MOFC or in other parts of the reward circuit that respond more to positively valenced stimuli (repetition enhancement), although enhancement effects were shown in some regions.

Attentional Bias to Food Images Associated With Elevated Weight and Future Weight Gain: An fMRI Study

Behavioral studies reveal that obese vs. lean individuals show attentional bias to food stimuli. Yet research has not investigated this relation using objective brain imaging or tested whether attentional bias to food stimuli predicts future weight gain, which are important aims given the prominence of food cues in the environment. We used functional magnetic resonance imaging (fMRI) to examine attentional bias in 35 adolescent girls ranging from lean to obese using an attention network task involving food and neutral stimuli. BMI correlated positively with speed of behavioral response to both appetizing food stimuli and unappetizing food stimuli, but not to neutral stimuli. BMI correlated positively with activation in brain regions related to attention and food reward, including the anterior insula/frontal operculum, lateral orbitofrontal cortex (OFC), ventrolateral prefrontal cortex (vlPFC), and superior parietal lobe, during initial orientation to food cues. BMI also correlated with greater activation in the anterior insula/frontal operculum during reallocation of attention to appetizing food images and with weaker activation in the medial OFC and ventral pallidum during reallocation of attention to unappetizing food images. Greater lateral OFC activation during initial orientation to appetizing food cues predicted future increases in BMI. Results indicate that overweight is related to greater attentional bias to food cues and that youth who show elevated reward circuitry responsivity during food cue exposure are at increased risk for weight gain.

Effects of Varenicline on Smoking Cue–Triggered Neural and Craving Responses

Varenicline, an effective smoking cessation medication, functions as an α4β2 nicotinic acetylcholine receptor partial agonist. It indirectly affects the dopaminergic reward system by reducing withdrawal symptoms during abstinence and by decreasing the reinforcement received from nicotine while smoking. We hypothesize that varenicline would have a third mechanism to blunt responses to smoking cues in the reward-related ventral striatum and medial orbitofrontal cortex and would be associated with a reduction in smoking cue–elicited craving. A laboratory model of conditioned responding and arterial spin-labeled perfusion functional magnetic resonance imaging, a biomarker of regional brain activity, was used to test our hypothesis. Perfusion functional magnetic resonance imaging is quantitative and stable across time, facilitating the measurement of medication-induced neural modifications in the brain in response to a challenge (smoking cue exposure) and in the brain in the resting condition (without provocation). Smokers were imaged during rest and during smoking cue exposure before and after a 3-week randomized placebo-controlled medication regimen. Subjects were nonabstinent to explicitly examine the effects of varenicline on cue reactivity independent of withdrawal. Center for the Study of Addictions, University of Pennsylvania, Philadelphia. Subjects Subjects were nicotine-dependent smokers who responded to advertisements placed on local radio and Listservs to participate in a medication-related research study that specifically stated "this is not a Quit Smoking Study" and "smokers may be contemplating but not currently considering quitting." Prerandomization smoking cues vs nonsmoking cues activated the ventral striatum and medial orbitofrontal cortex (t = 3.77) and elicited subjective reports of craving (P = .006). Craving reports correlated with increased activity in the posterior cingulate (t = 4.11). Administration of varenicline diminished smoking cue–elicited ventral striatum and medial orbitofrontal cortex responses (t values from –3.75 to –5.63) and reduced self-reported smoking cue–elicited craving, whereas placebo-treated subjects exhibited responses similar to those observed prior to randomization. Varenicline-induced activation of lateral orbitofrontal cortex in the brain at rest (t = 5.63) predicted blunting of smoking cue responses in the medial orbitofrontal cortex (r = –0.74). Varenicline's reciprocal actions in the reward-activated medial orbitofrontal cortex and in the reward-evaluating lateral orbitofrontal cortex underlie a diminished smoking cue response, revealing a distinctive new action that likely contributes to its clinical efficacy.

Decreased activation of lateral orbitofrontal cortex during risky choices under uncertainty is associated with disadvantageous decision-making and suicidal behavior

Decision-making impairment has been linked to orbitofrontal cortex lesions and to different disorders including substance abuse, aggression and suicidal behavior. Understanding the neurocognitive mechanisms of these impairments could facilitate the development of effective treatments. In the current study, we aimed to explore the neural and cognitive basis of poor decision-making ability associated with the vulnerability to suicidal behavior, a public health issue in most western countries. Twenty-five not currently depressed male patients, 13 of whom had a history of suicidal acts (suicide attempters) and 12 of whom had none (affective controls), performed an adapted version of the Iowa Gambling Task during functional Magnetic Resonance Imaging. Task-related functional Regions-of-Interest were independently defined in 15 male healthy controls performing the same task (Lawrence et al., 2009). In comparison to affective controls, suicide attempters showed 1) poorer performance on the gambling task 2) decreased activation during risky relative to safe choices in left lateral orbitofrontal and occipital cortices 3) no difference for the contrast between wins and losses. Altered processing of risk under conditions of uncertainty, associated with left lateral orbitofrontal cortex dysfunction, could explain the decision-making deficits observed in suicide attempters. These impaired cognitive and neural processes may represent future predictive markers and therapeutic targets in a field where identification of those at risk is poor and specific treatments are lacking. These results also add to our growing understanding of the role of the orbitofrontal cortex in decision-making and psychopathology.

A preliminary study of orbitofrontal activation and hypersociability in Williams Syndrome.

Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. Methods: We performed an event-related functional magnetic resonance imaging study while individuals with WS and typically developing controls (TD) matched positive and negative emotional faces. WS compared to TD showed reduced right amygdala activation during presentation of negative faces, as in the previous literature. In addition, WS showed a unique pattern of right orbitofrontal cortex activation. While TD showed medial orbitofrontal cortex activation in response to positive, and lateral orbitofrontal cortex activation to negative, WS showed the opposite pattern. In light of the general notion of a medial/lateral gradient of reward/punishment processing in the orbitofrontal cortex, these findings provide an additional biological explanation for, or correlate of positive attribution bias and hypersociability in WS.

Fasting biases brain reward systems towards high‐calorie foods

Nutritional state (e.g. fasted vs. fed) and different food stimuli (e.g. high-calorie vs. low-calorie, or appetizing vs. bland foods) are both recognized to change activity in brain reward systems. Using functional magnetic resonance imaging, we have studied the interaction between nutritional state and different food stimuli on brain food reward systems. We examined how blood oxygen level-dependent activity within a priori regions of interest varied while viewing pictures of high-calorie and low-calorie foods. Pictures of non-food household objects were included as control stimuli. During scanning, subjects rated the appeal of each picture. Twenty non-obese healthy adults [body mass index 22.1 +/- 0.5 kg/m(2) (mean +/- SEM), age range 19-35 years, 10 male] were scanned on two separate mornings between 11:00 and 12:00 h, once after eating a filling breakfast ('fed': 1.6 +/- 0.1 h since breakfast), and once after an overnight fast but skipping breakfast ('fasted': 15.9 +/- 0.3 h since supper) in a randomized cross-over design. Fasting selectively increased activation to pictures of high-calorie over low-calorie foods in the ventral striatum, amygdala, anterior insula, and medial and lateral orbitofrontal cortex (OFC). Furthermore, fasting enhanced the subjective appeal of high-calorie more than low-calorie foods, and the change in appeal bias towards high-calorie foods was positively correlated with medial and lateral OFC activation. These results demonstrate an interaction between homeostatic and hedonic aspects of feeding behaviour, with fasting biasing brain reward systems towards high-calorie foods.

Neural mechanisms supporting flexible performance adjustment during development

Feedback processing is crucial for successful performance adjustment following changing task demands. The present event-related fMRI study was aimed at investigating the developmental differences in brain regions associated with different aspects of feedback processing. Children age 8-11, adolescents age 14-15, and adults age 18-24 performed a rule switch task resembling the Wisconsin Card Sorting Task, and analyses focused on different types of negative and positive feedback. All age groups showed more activation in lateral orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and superior parietal cortex following negative relative to positive performance feedback, but the regions contributed to different aspects of feedback processing and had separable developmental trajectories. OFC was adultlike by age 8-11, whereas parietal cortex was adultlike by age 14-15. DLPFC and ACC, in contrast, were still developing after age 14-15. These findings demonstrate that changes in separable neural systems underlie developmental differences in flexible performance adjustment. Supplementary data from this study are available online at the Psychonomic Society Archive of Norms, Stimuli, and Data, at www.psychonomic.org/archive.