Separable neural mechanisms contribute to feedback processing in a rule-learning task

To adjust performance appropriately to environmental demands, it is important to monitor ongoing action and process performance feedback for possible errors. In this study, we used fMRI to test whether medial prefrontal cortex (PFC)/anterior cingulate cortex (ACC) and dorsolateral (DL) PFC have different roles in feedback processing. Twenty adults completed a rule-switch task in which rules had to be inferred on the basis of positive and negative feedback and the rules could change unexpectedly. Negative feedback resulted in increased activation in medial PFC/ACC and DLPFC relative to positive feedback, but the regions were differentially active depending on the type of negative feedback. Whereas medial PFC/ACC was most active following unexpected feedback indicating that prior performance was no longer correct, DLPFC was most active following negative feedback that was informative for correct behavior on the next trial. The current findings show that inconsistent results about the role of prefrontal cortex regions in feedback processing are most likely associated with the informative value of the performance feedback. The results are consistent with the hypothesis that medial PFC/ACC is important for signaling expectation violation whereas DLPFC is important for goal-directed actions.     

Neural substrates of choice selection in adults and adolescents: development of the ventrolateral prefrontal and anterior cingulate cortices

A heightened propensity for risk-taking and poor decision-making underlies the peak morbidity and mortality rates reported during adolescence. Delayed maturation of cortical structures during the adolescent years has been proposed as a possible explanation for this observation. Here, we test the hypothesis of adolescent delayed maturation by using fMRI during a monetary decision-making task that directly examines risk-taking behavior during choice selection. Orbitofrontal/ventrolateral prefrontal cortex (OFC/VLPFC) and dorsal anterior cingulate cortex (ACC) were examined selectively since both have been implicated in reward-related processes, cognitive control, and resolution of conflicting decisions. Group comparisons revealed greater activation in the OFC/VLPFC (BA 47) and dorsal ACC (BA 32) in adults than adolescents when making risky selections. Furthermore, reduced activity in these areas correlated with greater risk-taking performance in adolescents and in the combined group. Consistent with predictions, these results suggest that adolescents engage prefrontal regulatory structures to a lesser extent than adults when making risky economic choices.     

Common and distinct networks underlying reward valence and processing stages: a meta-analysis of functional neuroimaging studies

To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore take distributed and interrelated representations of reward valuation and valence assessment into account.     

Brain responses to success and failure: Direct recordings from human cerebral cortex

Evaluating the outcome of our own actions is a fundamental process by which we adapt our behavior in our interaction with the external world. fMRI and electrophysiological studies in monkeys have found feedback‐specific responses in several brain regions, unveiling facets of a large‐scale network predominantly distributed in the frontal lobes. However, a consensus has yet to be reached regarding the exact contribution of each region. The present study benefited from intracerebral EEG recordings in epileptic patients to record directly the neural activity in each of those frontal structures in response to positive and negative feedback. Both types of feedback induced a sequence of high‐frequency responses (>40 Hz) in a widespread network involving medial frontal cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and insular cortex. The pre‐supplementary motor area (pre‐SMA), DLPFC, and lateral OFC showed higher activation in response to negative feedback, while medial OFC and dorsal anterior cingulate cortex (dACC) were more responsive to positive feedback. Responses in the medial prefrontal cortex (pre‐SMA and dACC) were sustained (lasting more than 1,000 ms), while responses in the DLPFC, insula, and the OFC were short lasting (less than 800 ms). Taken together, our findings show that evaluating the outcome of our actions triggers γ‐range activity modulations in several frontal and insular regions. Moreover, we found that the timing and amplitude of those γ‐band responses reveal fine‐scale dissociations between the neural dynamics of positive versus negative feedback processing. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Neural circuitry underlying voluntary suppression of sadness.

BACKGROUND: The ability to voluntarily self-regulate negative emotion is essential to a healthy psyche. Indeed, a chronic incapacity to suppress negative emotion might be a key factor in the genesis of depression and anxiety. Regarding the neural underpinnings of emotional self-regulation, a recent functional neuroimaging study carried out by our group has revealed that the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex are involved in voluntary suppression of sexual arousal. As few things are known, still, with respect to the neural substrate underlying volitional self-regulation of basic emotions, here we used functional magnetic resonance imaging to identify the neural circuitry associated with the voluntary suppression of sadness. METHODS: Twenty healthy female subjects were scanned during a Sad condition and a Suppression condition. In the Sad condition, subjects were instructed to react normally to sad film excerpts whereas, in the Suppression condition, they were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. RESULTS: Transient sadness was associated with significant loci of activation in the anterior temporal pole and the midbrain, bilaterally, as well as in the left amygdala, left insula, and right ventrolateral prefrontal cortex (VLPFC) (Brodmann area [BA] 47). Correlational analyses carried out between self-report ratings of sadness and regional blood oxygen level dependent (BOLD) signal changes revealed the existence of positive correlations in the right VLPFC (BA 47), bilaterally, as well as in the left insula and the affective division of the left anterior cingulate gyrus (BA 24/32). In the Suppression condition, significant loci of activation were noted in the right DLPFC (BA 9) and the right orbitofrontal cortex (OFC) (BA 11), and positive correlations were found between the self-report ratings of sadness and BOLD signal changes in the right OFC (BA 11) and right DLPFC (BA 9). CONCLUSIONS: These results confirm the key role played by the DLPFC in emotional self-regulation. They also indicate that the right DLPFC and right OFC are components of a neural circuit implicated in voluntary suppression of sadness.     

Prefrontal cortex and drug abuse vulnerability: Translation to prevention and treatment interventions

Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals.     

Switching between colors and shapes on the basis of positive and negative feedback: an fMRI and EEG study on feedback-based learning

A crucial element of testing hypotheses about rules for behavior is the use of performance feedback. In this study, we used fMRI and EEG to test the role of medial prefrontal cortex (PFC) and dorsolateral (DL) PFC in hypothesis testing using a modified intradimensional/extradimensional rule shift task. Eighteen adults were asked to infer rules about color or shape on the basis of positive and negative feedback in sets of two trials. Half of the trials involved color-to-color or shape-to-shape trials (intradimensional switches; ID) and the other half involved color-to-shape or shape-to-color trials (extradimensional switches; ED). Participants performed the task in separate fMRI and EEG sessions. ED trials were associated with reduced accuracy relative to ID trials. In addition, accuracy was reduced and response latencies increased following negative relative to positive feedback. Negative feedback resulted in increased activation in medial PFC and DLPFC, but more so for ED than ID shifts. Reduced accuracy following negative feedback correlated with increased activation in DLPFC, and increased response latencies following negative feedback correlated with increased activation in medial PFC. Additionally, around 250 msec following negative performance feedback participants showed a feedback-related negative scalp potential, but this potential did not differ between ID and ED shifts. These results indicate that both medial PFC and DLPFC signal the need for performance adjustment, and both regions are sensitive to the increased demands of set shifting in hypothesis testing.     

Differential activation of ventrolateral prefrontal cortex during working memory retrieval

Brain imaging studies have suggested a predominant involvement of prefrontal areas during retrieval of information from working memory (WM). This study used event-related functional magnetic resonance imaging to assess the gradual recruitment of brain areas during verbal WM-retrieval with a parametrically varied modified version of the Sternberg Item Recognition Paradigm. In particular, we were interested in activation differences during retrieval of negative and positive probes. Fifteen subjects performed a WM-task which required the retrieval of a probe letter from a set of a maximum of three letters. The analysis of the retrieval period regardless of probe type revealed bilateral VLPFC activation during retrieval from a single remembered item. These initially activated regions showed a gradual activation increase of left VLPFC (BA 47) and anterior PFC (BA 10) as well as and bilateral DLPFC (BA 9) with increasing retrieval demand, i.e. during retrieval of two and three previously remembered letters. The comparison of negative and positive probes (non-targets versus targets) revealed greater activity in VLPFC (BA 47) in response to negative than to positive probes. These findings demonstrate that ventral areas of prefrontal cortex seem to be differentially engaged during the discrimination of a non-target from a previously manipulated set.     

Fronto-limbic function in unaffected offspring at familial risk for bipolar disorder during an emotional working memory paradigm

Evidence from neuroimaging studies indicate that individuals with bipolar disorder (BD) exhibit altered functioning of fronto-limbic systems implicated in voluntary emotion regulation. Few studies, however, have examined the extent to which unaffected youth at familial risk for BD exhibit such alterations. Using an fMRI emotional working memory paradigm, we investigated the functioning of fronto-limbic systems in fifteen healthy bipolar offspring (8–17 years old) with at least one parent diagnosed with BD (HBO), and 16 age-matched healthy control (HC) participants. Neural activity and functional connectivity analyses focused on a priori neural regions supporting emotion processing (amygdala and ventral striatum) and voluntary emotion regulation (ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC)). Relative to HC, HBO exhibited greater right VLPFC (BA47) activation in response to positive emotional distracters and reduced VLPFC modulation of the amygdala to both the positive and negative emotional distracters; there were no group differences in connectivity for the neutral distracters. These findings suggest that alterations in the functioning of fronto-limbic systems implicated in voluntary emotion regulation are present in unaffected bipolar offspring. Future longitudinal studies are needed to determine the extent to which such alterations represent neurodevelopmental markers of risk for future onset of BD.     

Differential cerebral activation during observation of expressive gestures and motor acts

We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (fMRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Broca's and Wernicke's areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures.     

Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task

An important function of the prefrontal cortex (PFC) is the control of goal-directed behaviour. This requires information as to whether actions were successful in obtaining desired outcomes such as rewards. While lesion studies implicate a particular PFC region, the orbitofrontal cortex (OFC), in reward processing, neurons encoding reward have been reported in both the OFC and the dorsolateral prefrontal cortex (DLPFC). To compare and contrast their roles, we recorded simultaneously from both areas while two rhesus monkeys (Macaca mulatta) performed a reward preference task. The monkeys had to choose between pictures associated with different amounts of a juice reward. Neuronal activity in both areas reflected the reward amount. However, neurons in the DLPFC encoded both the reward amount and the monkeys' forthcoming response, while neurons in the OFC more often encoded the reward amount alone. Further, reward selectivity arose more rapidly in the OFC than the DLPFC. These results are consistent with reward information entering the PFC via the OFC, where it is passed to the DLPFC and used to control behaviour.     

Comprehensive examination of frontal regions in boys and girls with attention-deficit/hyperactivity disorder

The current study examined regional frontal lobe volumes based on functionally relevant subdivisions in contemporaneously recruited samples of boys and girls with and without attention-deficit/hyperactivity disorder (ADHD). Forty-four boys (21 ADHD, 23 control) and 42 girls (21 ADHD, 21 control), ages 8-13 years, participated. Sulcal-gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: primary motor cortex, anterior cingulate, deep white matter, premotor regions [supplementary motor complex (SMC), frontal eye field, lateral premotor cortex (LPM)], and prefrontal cortex (PFC) regions [medial PFC, dorsolateral PFC (DLPFC), inferior PFC, lateral orbitofrontal cortex (OFC), and medial OFC]. Compared to sex-matched controls, boys and girls with ADHD showed reduced volumes (gray and white matter) in the left SMC. Conversely, girls (but not boys) with ADHD showed reduced gray matter volume in left LPM; while boys (but not girls) with ADHD showed reduced white matter volume in left medial PFC. Reduced left SMC gray matter volumes predicted increased go/no-go commission rate in children with ADHD. Reduced left LPM gray matter volumes predicted increased go/no-go variability, but only among girls with ADHD. Results highlight different patterns of anomalous frontal lobe development among boys and girls with ADHD beyond that detected by measuring whole lobar volumes.     

The VLPFC versus the DLPFC in Downregulating Social Pain Using Reappraisal and Distraction Strategies

The dorsolateral prefrontal cortex (DLPFC) and ventrolateral PFC (VLPFC) are both crucial structures involved in voluntary emotional regulation. However, it remains unclear whether the functions of these two cortical regions that are involved in emotional regulation, which are usually active in non-social situations, could be generalized to the regulation of social pain as well. This study employed transcranial magnetic stimulation (TMS) to examine the causal relationship between the DLPFC/VLPFC and the emotional regulation of social pain via distraction and reappraisal. Ninety human participants (45 males and 45 females) initially underwent either active (DLPFC/VLPFC, n = 30/30) or sham (vertex, n = 30) TMS sessions. Participants were then instructed to use both distraction and reappraisal strategies to downregulate any negative emotions evoked by social exclusion pictures. Convergent results of the subjective emotional rating and electrophysiological indices demonstrated that: (1) both the DLPFC and VLPFC highly facilitate the downregulation of affective responses caused by social exclusion, revealing a causal role of these lateral PFCs in voluntary emotional regulation of both non-social and social pain; and (2) these two cortical regions showed relative functional specificity for distraction (DLPFC) and reappraisal (VLPFC) strategies, which helps to refine the cortical targeting of therapeutic protocols. In addition, the TMS effect was sustainable for at least 1 h, showcasing the potential feasibility of using this method in clinical practice. Together, these findings provide cognitive and neural evidence for the targeting of the VLPFC and/or the DLPFC to improve emotional regulation abilities, especially in social contexts.SIGNIFICANCE STATEMENT This study aimed to examine the role of the dorsolateral prefrontal cortex (DLPFC) and ventrolateral PFC (VLPFC) in emotional regulation, particularly in response to social pain through the use of distraction and reappraisal strategies, as this is a relatively underexplored area of inquiry. This study makes a significant contribution to the literature because our results provide novel empirical information on the role of these cortical structures in the processing of negative emotions elicited within certain social contexts. As such, our findings have potential clinical implications, paving the way for future clinicians to be able to accurately target specific brain regions among patients struggling with impaired social cognition abilities, including those diagnosed with posttraumatic stress disorder, autism spectrum disorder, social anxiety disorder, and depression.     

Separate neural systems for behavioral change and for emotional responses to failure during behavioral inhibition

To analyze the involvement of different brain regions in behavioral inhibition and impulsiveness, differences in activation were investigated in fMRI data from a response inhibition task, the stop‐signal task, in 1709 participants. First, areas activated more in stop‐success (SS) than stop‐failure (SF) included the lateral orbitofrontal cortex (OFC) extending into the inferior frontal gyrus (ventrolateral prefrontal cortex, BA 47/12), and the dorsolateral prefrontal cortex (DLPFC). Second, the anterior cingulate and anterior insula (AI) were activated more on failure trials, specifically in SF versus SS. The interaction between brain region and SS versus SF activations was significant (P = 5.6 * 10^?8). The results provide new evidence from this “big data” investigation consistent with the hypotheses that the lateral OFC is involved in the stop‐related processing that inhibits the action; that the DLPFC is involved in attentional processes that influence task performance; and that the AI and anterior cingulate are involved in emotional processes when failure occurs. The investigation thus emphasizes the role of the human lateral OFC BA 47/12 in changing behavior, and inhibiting behavior when necessary. A very similar area in BA47/12 is involved in changing behavior when an expected reward is not obtained, and has been shown to have high functional connectivity in depression. Hum Brain Mapp 38:3527–3537, 2017 . © 2017 Wiley Periodicals, Inc.     

Prefrontal contributions to domain-general executive control processes during temporal context retrieval

Neuroimaging studies have reported increased prefrontal cortex (PFC) activity during temporal context retrieval versus recognition memory. However, it remains unclear if these activations reflect PFC contributions to domain-general executive control processes or domain-specific retrieval processes. To gain a better understanding of the functional roles of these various PFC regions during temporal context retrieval we propose it is necessary to examine PFC activity across tasks from different domains, in which parallel manipulations are included targeting specific cognitive processes. In the current fMRI study, we examined domain-general and domain-specific PFC contributions to temporal context retrieval by increasing stimulus (but maintaining response number) and increasing response number (but maintaining stimulus number) across temporal context memory and ordering control tasks, for faces. The control task required subjects to order faces from youngest to oldest. Our behavioral results indicate that the combination of increased stimulus and response numbers significantly increased task difficulty for temporal context retrieval and ordering tasks. Across domains, increasing stimulus number, while maintaining response numbers, caused greater right lateral premotor cortex (BA 6/8) activity; whereas increasing response number, while maintaining stimulus number, caused greater domain-general left DLPFC (BA 9) and VLPFC (BA 44/45) activity. In addition, we found domain-specific right DLPFC (BA 9) activity only during retrieval events. These results highlight the functional heterogeneity of frontal cortex, and suggest its involvement in temporal context retrieval is related to its role in various cognitive control processes.     

Neural correlates of sad feelings in schizophrenia with and without blunted affect.

OBJECTIVE: There have been reports that patients with schizophrenia have decreased activity in the prefrontal cortex during emotion processing. However, findings have been confounded by sample nonspecificity and explicit cognitive task interference with emotion processing. We aimed to further investigate this by examining the ventrolateral prefrontal cortex (VLPFC) activation in response to the passive viewing of sad film excerpts. METHODS: We presented film excerpts depicting sad and neutral social situations to 25 schizophrenia patients (14 with blunted affect [BA+] and 11 without blunted affect [BA-]) in an implicit perception task to evoke prefronto-limbic activity illustrated by blood oxygenation level-dependent functional magnetic resonance imaging. RESULTS: A random-effects analysis (2-sample t test) using statistical parametric mapping indicated that BA+ patients differed from BA- patients at a 0.05 level (P corrected for multiple comparisons). Consistent with our a priori hypothesis, BA- patients (relative to BA+ patients) showed significant activation in the right VLPFC. An exploratory analysis revealed the following loci of activation: caudate nucleus, VLPFC, middle prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, and anterior temporal pole in the BA- group; and hippocampus, cerebellum, anterior temporal pole, and midbrain in the BA+ group. CONCLUSIONS: We observed not only hypofrontality in the BA+ group but also dysfunctional circuitry distributed throughout the brain. The temporal and midbrain activation seen in the BA+ group may indicate that these brain regions were working harder to compensate for inactivation in other regions. These distributed dysfunctional circuits may form the neural basis of blunted affect through impairment of emotion processing in the brain that prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as blunted affect.     

Heritability of aggression following social evaluation in middle childhood: An fMRI study

Middle childhood marks an important phase for developing and maintaining social relations. At the same time, this phase is marked by a gap in our knowledge of the genetic and environmental influences on brain responses to social feedback and their relation to behavioral aggression. In a large developmental twin sample (509 7‐ to 9‐year‐olds), the heritability and neural underpinnings of behavioral aggression following social evaluation were investigated, using the Social Network Aggression Task (SNAT). Participants viewed pictures of peers that gave positive, neutral, or negative feedback to the participant's profile. Next, participants could blast a loud noise toward the peer as an index of aggression. Genetic modeling revealed that aggression following negative feedback was influenced by both genetics and environmental (shared as well as unique environment). On a neural level (n = 385), the anterior insula and anterior cingulate cortex gyrus (ACCg) responded to both positive and negative feedback, suggesting they signal for social salience cues. The medial prefrontal cortex (mPFC) and inferior frontal gyrus (IFG) were specifically activated during negative feedback, whereas positive feedback resulted in increased activation in caudate, supplementary motor cortex (SMA), and dorsolateral prefrontal cortex (DLPFC). Decreased SMA and DLPFC activation during negative feedback was associated with more aggressive behavior after negative feedback. Moreover, genetic modeling showed that 13%–14% of the variance in dorsolateral PFC activity was explained by genetics. Our results suggest that the processing of social feedback is partly explained by genetic factors, whereas shared environmental influences play a role in behavioral aggression following feedback.     

Neural correlates of automatic beliefs about gender and race

Functional MRI was used to identify the brain areas underlying automatic beliefs about gender and race, and suppression of those attitudes. Participants (n = 20; 7 females) were scanned at 3 tesla while performing the Implicit Association Test (IAT), an indirect measure of race and gender bias. We hypothesized that ventromedial prefrontal cortex areas (PFC) would mediate gender and racial stereotypic attitudes, and suppression of these beliefs would recruit dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC). Performance data on the IAT revealed gender and racial biases. Racial bias was correlated with an explicit measure of racism. Results showed activation of anteromedial PFC and rostral ACC while participants implicitly made associations consistent with gender and racial biases. In contrast, associations incongruent with stereotypes recruited DLPFC. Implicit gender bias was correlated with amygdala activation during stereotypic conditions. Results suggest there are dissociable roles for anteromedial and dorsolateral PFC circuits in the activation and inhibition of stereotypic attitudes.     

Neurobiology of decision-making in adolescents

The study examined the relationship between risk-taking behavior during selection of monetary rewards and activations in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), brain regions that are associated with decision-making. Thirty-three adolescents with no personal or family history of any psychiatric illness were administered the Wheel of Fortune (WOF) task using a functional magnetic resonance imaging protocol. The WOF is a computerized two-choice, probabilistic monetary reward task. Selection of a reward, particularly a low-probability/high-magnitude reward choice, induced greater activations in dorsal ACC, ventrolateral OFC and mPFC than the control condition. Although similar findings have been reported by earlier studies, the results from this study were not impacted by reaction times and expected values and persisted even after controlling for sociodemographic factors. Post hoc analysis revealed greater activation of ACC and mPFC in response to selection of rewards of larger magnitude than those of smaller magnitude when the probability of reward was maintained constant. Adolescents with greater frequency of high-risk behavior (defined as low-probability/high-magnitude reward choice) had lower activation of ACC, OFC and mPFC than those who engaged in this behavior less frequently. These findings suggest individual differences in prefrontal cortical function with regards to decision-making process in adolescents.     

Prefrontal cortex involvement in processing incorrect arithmetic equations: evidence from event-related fMRI

The main aim of this study was to investigate the differential processing of correct and incorrect equations to gain further insight into the neural processes involved in arithmetic reasoning. Electrophysiological studies in humans have demonstrated that processing incorrect arithmetic equations (e.g., 2 + 2 = 5) elicits a prominent event-related potential (ERP) compared to processing correct equations (e.g., 2 + 2 = 4). In the present study, we investigated the neural substrates of this process using event-related functional magnetic resonance imaging (fMRI). Subjects were presented with arithmetic equations and asked to indicate whether the solution displayed was correct or incorrect. We found greater activation to incorrect, compared to correct equations, in the left dorsolateral prefrontal cortex (DLPFC, BA 46) and the left ventrolateral prefrontal cortex (VLPFC, BA 47). Our results provide the first brain imaging evidence for differential processing of incorrect vs. correct equations. The prefrontal cortex activation observed in processing incorrect equations overlaps with brain areas known to be involved in working memory and interference processing. The DLPFC region differentially activated by incorrect equations was also involved in overall arithmetic processing, whereas the VLPFC was activated only during the differential processing of incorrect equations. Differential response to correct and incorrect arithmetic equations was not observed in parietal cortex regions such as the angular gyrus and intra-parietal sulcus, which are known to play a specific role in performing arithmetic computations. The pattern of brain response observed is consistent with the hypothesis that processing incorrect equations involves detection of an incorrect answer and resolution of the interference between the internally computed and externally presented incorrect answer. More specifically, greater activation during processing of incorrect equations appears to reflect additional operations involved in maintaining the results in working memory, while subjects attempt to resolve the conflict and select a response. These findings allow us to further delineate and dissociate the contributions of prefrontal and parietal cortices to arithmetic reasoning.