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.     

Politics on the brain: an FMRI investigation

We assessed political attitudes using the Implicit Association Test (IAT) in which participants were presented faces and names of well-known Democrat and Republican politicians along with positive and negative words while undergoing functional MRI. We found a significant behavioral IAT effect for the face, but not the name, condition. The fMRI face condition results indicated that ventromedial and anterior prefrontal cortices were activated during political attitude inducement. Amygdala and fusiform gyrus were activated during perceptual processing of familiar faces. Amygdala activation also was associated with measures of strength of emotion. Frontopolar activation was positively correlated with an implicit measure of bias and valence strength (how strongly the participants felt about the politicians), while strength of affiliation with political party was negatively correlated with lateral PFC, lending support to the idea that two distinct but interacting networks-one emphasizing rapid, stereotypic, and emotional associative knowledge and the other emphasizing more deliberative and factual knowledge-cooperate in the processing of politicians. Our findings of ventromedial PFC activation suggests that when processing the associative knowledge concerned with politicians, stereotypic knowledge is activated, but in addition, the anterior prefrontal activations indicate that more elaborative, reflective knowledge about the politician is activated.     

Politics on the brain: An fMRI investigation

Abstract

We assessed political attitudes using the Implicit Association Test (IAT) in which participants were presented with faces and names of well-known Democrat and Republican politicians along with positive and negative words while undergoing functional MRI. We found a significant behavioral IAT effect for the face, but not the name, condition. The fMRI face condition results indicated that ventromedial and anterior prefrontal cortices were activated during political attitude inducement. Amygdala and fusiform gyrus were activated during perceptual processing of familiar faces. Amygdala activation was also associated with measures of strength of emotion. Frontopolar activation was positively correlated with an implicit measure of bias and valence strength (how strongly the participants felt about the politicians), while strength of affiliation with political party was negatively correlated with lateral PFC, lending support to the idea that two distinct but interacting networks—one emphasizing rapid, stereotypic, and emotional associative knowledge and the other emphasizing more deliberative and factual knowledge—co-operate in the processing of politicians. Our findings of ventromedial PFC activation suggests that when processing the associative knowledge concerned with politicians, stereotypic knowledge is activated, but, in addition, the anterior prefrontal activations indicate that more elaborative, reflective knowledge about the politician is activated.     

Intact performance on an indirect measure of race bias following amygdala damage

Recent brain imaging and lesion studies provide converging evidence for amygdala involvement in judgments of fear and trust based on facial expression [Adolphs et al., Nature 393 (1998) 470; Adolphs et al., Neuropsychologia 37 (1999) 1111; Breiter et al., Neuron 17 (1996) 875; Winston et al., Nat. Neurosci. 5 (3) (2002) 277]. Another type of social information apparent in face stimuli is social group membership. Imaging studies have reported amygdala activation to face stimuli of different racial groups [Hart et al., NeuroReport 11 (11) (2000) 2351]. In White American subjects, amygdala activation to Black versus White faces was correlated with indirect, implicit measures of racial evaluation [Phelps et al., J. Cogn. Neurosci. 12 (5) (2000) 729]. To determine if the amygdala plays a critical role in indirect social group evaluation, as suggested by the imaging results, a patient with bilateral amygdala damage and control subjects were given two measures of race bias. All subjects were female, White Americans. The Modern Racism Scale (MRS) is a direct, self-report measure of race attitudes and beliefs. The Implicit Association Test (IAT) is an indirect, automatic evaluation task. Performance on the two tasks did not differ between the patient with amygdala damage and control subjects. All subjects showed a pro-Black bias on the direct, explicit measure of race beliefs, the MRS, and a negative evaluation towards Black faces on the indirect measure of race evaluation, the IAT. These results indicate that even though amygdala activation to Black versus White faces is correlated with performance on indirect measures of race bias [Phelps et al., J. Cogn. Neurosci. 12 (5) (2000) 729], the amygdala is not critical for normal performance on the IAT.     

Negative stereotype activation alters interaction between neural correlates of arousal, inhibition and cognitive control

Priming negative stereotypes of African Americans can bias perceptions toward novel Black targets, but less is known about how these perceptions ultimately arise. Examining how neural regions involved in arousal, inhibition and control covary when negative stereotypes are activated can provide insight into whether individuals attempt to downregulate biases. Using fMRI, White egalitarian-motivated participants were shown Black and White faces at fast (32 ms) or slow (525 ms) presentation speeds. To create a racially negative stereotypic context, participants listened to violent and misogynistic rap (VMR) in the background. No music (NM) and death metal (DM) were used as control conditions in separate blocks. Fast exposure of Black faces elicited amygdala activation in the NM and VMR conditions (but not DM), that also negatively covaried with activation in prefrontal regions. Only in VMR, however, did amygdala activation for Black faces persist during slow exposure and positively covary with activation in dorsolateral prefrontal cortex while negatively covarying with activation in orbitofrontal cortex. Findings suggest that contexts that prime negative racial stereotypes seem to hinder the downregulation of amygdala activation that typically occurs when egalitarian perceivers are exposed to Black faces.     

The interaction of perceived control and Gambler's fallacy in risky decision making: An fMRI study

Limited recent evidence implicates the anterior/posterior cingulate (ACC/PCC) and lateral prefrontal networks as the neural substrates of risky decision‐making biases such as illusions of control (IoC) and gambler's fallacy (GF). However, investigation is lacking on the dynamic interactive effect of those biases during decision making. Employing a card‐guessing game that independently manipulates trial‐by‐trial perceived control and gamble outcome among 29 healthy female participants, we observed both IoC‐ and GF‐type behaviors, as well as an interactive effect of previous control and previous outcome, with GF‐type behaviors only following computer‐selected, but not self‐selected, outcomes. Imaging results implicated the ACC and left dorsolateral prefrontal cortex (DLPFC) in agency processing, and the cerebellum and right DLPFC in previous outcome processing, in accordance with past literature. Critically, the right inferior parietal lobule (IPL) exhibited significant betting‐related activities to the interaction of previous control and previous outcome, showing more positive signals to previous computer‐selected winning versus losing outcomes but the reverse pattern following self‐selected outcomes, as well as responding to the interactive effect of control and outcome during feedback. Associations were also found between participants' behavioral sensitivity to the interactive effect of previous control and previous outcome, and right IPL signals, as well as its functional connectivity with neural networks implicated in agency and previous outcome processing. We propose that the right IPL provides the neural substrate for the interaction of perceived control and GF, through coordinating activities in the anterior and posterior cingulate cortices and working conjunctively with lateral PFC and other parietal networks. Hum Brain Mapp 37:1218–1234, 2016. © 2016 Wiley Periodicals, Inc .     

The left dorsolateral prefrontal cortex and caudate pathway: New evidence for cue‐induced craving of smokers

Although the activation of the prefrontal cortex (PFC) and the striatum had been found in smoking cue induced craving task, whether and how the functional interactions and white matter integrity between these brain regions contribute to craving processing during smoking cue exposure remains unknown. Twenty‐five young male smokers and 26 age‐ and gender‐matched nonsmokers participated in the smoking cue‐reactivity task. Craving related brain activation was extracted and psychophysiological interactions (PPI) analysis was used to specify the PFC‐efferent pathways contributed to smoking cue‐induced craving. Diffusion tensor imaging (DTI) and probabilistic tractography was used to explore whether the fiber connectivity strength facilitated functional coupling of the circuit with the smoking cue‐induced craving. The PPI analysis revealed the negative functional coupling of the left dorsolateral prefrontal cortex (DLPFC) and the caudate during smoking cue induced craving task, which positively correlated with the craving score. Neither significant activation nor functional connectivity in smoking cue exposure task was detected in nonsmokers. DTI analyses revealed that fiber tract integrity negatively correlated with functional coupling in the DLPFC‐caudate pathway and activation of the caudate induced by smoking cue in smokers. Moreover, the relationship between the fiber connectivity integrity of the left DLPFC‐caudate and smoking cue induced caudate activation can be fully mediated by functional coupling strength of this circuit in smokers. The present study highlighted the left DLPFC‐caudate pathway in smoking cue‐induced craving in smokers, which may reflect top‐down prefrontal modulation of striatal reward processing in smoking cue induced craving processing. Hum Brain Mapp 38:4644–4656, 2017. © 2017 Wiley Periodicals, Inc.     

Neural correlates of developmental differences in risk estimation and feedback processing

The primary aim of this study was to compare the neural substrates of decision-making in middle-aged children and adults. To this end, we collected fMRI data while 9-12-year-olds and 18-26-year-olds performed a simple gambling task. The task was designed to tap two important aspects of decision-making: risk estimation and feedback processing. We examined how orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) contributed to risk estimation, and how ventrolateral and medial prefrontal cortices (VLPFC and medial PFC) contributed to negative feedback processing in children and adults. Region of interest analyses revealed differences in brain activation between children and adults for ACC and lateral OFC. ACC was recruited more for high-risk than for low-risk trials, and this difference was larger for children than for adults. In contrast, children and adults did not differ in activation for OFC or DLPFC. These data suggest that children's decision-making under uncertainty is associated with a high degree of response conflict. Both age groups exhibited bilateral VLPFC (BA 47) and medial PFC/ACC (BA 6/ BA 32 (dorsal) and 24 (ventral)) activation associated with negative feedback processing. Relative to adults, children engaged lateral OFC more strongly for negative relative to positive feedback. These results indicate that children may find negative feedback more aversive than adults do. In summary, children aged 9-12 years and adults recruit similar brain regions during risk-estimation and feedback processing, but some key differences between the groups provide insight into the factors contributing to developmental changes in decision-making.     

Aberrant visual circuitry associated with normal spatial match-to-sample accuracy in schizophrenia

A goal of this study was to evaluate the function of the anterior cingulate cortex (ACC) and of the dorsolateral prefrontal cortex (DLPFC) in medicated patients with schizophrenia (SZ), a small group of first-degree relatives, and healthy controls using a visual delayed match-to-sample task in conjunction with functional magnetic resonance imaging (fMRI). To mitigate performance differences between SZ and healthy controls, we used a novel task that allows for individualized adjustment of task difficulty to match ability level. We also trained participants on the task prior to scanning. Using an event-related design, we modeled three components of the match-to-sample trial: visual encoding, delay, and discrimination. We did not find significant differences in ACC/medial frontal cortex activation between the groups. However, compared to healthy controls, SZ showed decreased activation in visual processing areas during the encoding and discrimination phases of the task and in the ventrolateral prefrontal cortex during the delay. These findings emphasize the tendency of schizophrenia subjects to solve perceptual memory problems by engaging diverse regions.     

Neural correlates of switching set as measured in fast, event-related functional magnetic resonance imaging

Attentional switching has shown to involve several prefrontal and parietal brain regions. Most cognitive paradigms used to measure cognitive switching such as the Wisconsin Card Sorting Task (WCST) involve additional cognitive processes besides switching, in particular working memory (WM). It is, therefore, questionable whether prefrontal brain regions activated in these conditions, especially dorsolateral prefrontal cortex (DLPFC), are involved in cognitive switching per se, or are related to WM components involved in switching tasks. Functional magnetic resonance imaging (fMRI) was used to examine neural correlates of pure switching using a paradigm purposely designed to minimize WM functions. The switching paradigm required subjects to switch unpredictably between two spatial dimensions, clearly indicated throughout the task before each trial. Fast, event-related fMRI was used to compare neural activation associated with switch trials to that related to repeat trials in 20 healthy, right-handed, adult males. A large cluster of activation was observed in the right hemisphere, extending from inferior prefrontal and pre- and postcentral gyri to superior temporal and inferior parietal cortices. A smaller and more caudal cluster of homologous activation in the left hemisphere was accompanied by activation of left dorsolateral prefrontal cortex (DLPFC). We conclude that left DLPFC activation is involved directly in cognitive switching, in conjunction with parietal and temporal brain regions. Pre- and postcentral gyrus activation may be related to motor components of switching set.     

Alterations in functional activation in euthymic bipolar disorder and schizophrenia during a working memory task

Dysfunctions in prefrontal cortical networks are thought to underlie working memory (WM) impairments consistently observed in both subjects with bipolar disorder and schizophrenia. It remains unclear, however, whether patterns of WM‐related hemodynamic responses are similar in bipolar and schizophrenia subjects compared to controls. We used fMRI to investigate differences in blood oxygen level dependent activation during a WM task in 21 patients with euthymic bipolar I, 20 patients with schizophrenia, and 38 healthy controls. Subjects were presented with four stimuli (abstract designs) followed by a fifth stimulus and required to recall whether the last stimulus was among the four presented previously. Task‐related brain activity was compared within and across groups. All groups activated prefrontal cortex (PFC), primary and supplementary motor cortex, and visual cortex during the WM task. There were no significant differences in PFC activation between controls and euthymic bipolar subjects, but controls exhibited significantly increased activation (cluster‐corrected P < 0.05) compared to patients with schizophrenia in prefrontal regions including dorsolateral prefrontal cortex (DLPFC). Although the bipolar group exhibited intermediate percent signal change in a functionally defined DLPFC region of interest with respect to the schizophrenia and control groups, effects remained significant only between patients with schizophrenia and controls. Schizophrenia and bipolar disorder may share some behavioral, diagnostic, and genetic features. Differences in the patterns of WM‐related brain activity across groups, however, suggest some diagnostic specificity. Both patient groups showed some regional task‐related hypoactivation compared to controls across the brain. Within DLPFC specifically, patients with schizophrenia exhibited more severe WM‐related dysfunction than bipolar subjects. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Elevation of cell adhesion molecule immunoreactivity in the anterior cingulate cortex in bipolar disorder.

BACKGROUND: Neuroimaging reports of increases in signal hyperintensities in white and deep gray matter and other work indicate that there might be an inflammatory response in affective disorders. METHODS: The microvascular immunoreactivity of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 was measured with image analysis in postmortem tissue from the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) from 15 unipolar and 15 bipolar subjects and compared with each other and with 15 subjects with schizophrenia and 15 control subjects. RESULTS: Intercellular adhesion molecule-1 immunoreactivity in gray and white matter of the ACC in bipolar subjects was increased compared with control subjects (gray: p =.001; white: p <.001) and schizophrenic subjects (gray: p =.016; white: p =.025) and modestly increased in white matter compared with unipolar subjects (p =.049). No such differences were found in the DLPFC. CONCLUSIONS: These findings are consistent with the presence of an inflammatory response in the ACC in bipolar disorder.     

Dissociable effects of prefrontal and anterior temporal cortical lesions on stereotypical gender attitudes

Clinical observations of patients with ventral frontal and anterior temporal cortical lesions reveal marked abnormalities in social attitudes. A previous study in seven patients with ventral prefrontal lesions provided the first direct experimental evidence for abnormalities in social attitudes using a well-established measure of gender stereotypes, the Implicit Association Test (IAT). Here, we were able to test whether these first findings could be reproduced in a larger sample of 154 patients with penetrating head injuries, and to determine the differential effects of ventromedial prefrontal (vmPFC) and ventrolateral prefrontal (vlPFC) cortical lesions on IAT performance. In addition, we investigated the role of the superior anterior temporal lobe (aTL), recently shown to represent conceptual social knowledge. First, we used a linear regression model to identify the role of each of the three regions, while controlling for the extent of damage to other regions. We found that larger lesions in either the vmPFC or the superior aTL were associated with increased stereotypical attitudes, whereas larger lesions in the vlPFC were associated with decreased stereotypical attitudes. Second, in a confirmatory analysis, we grouped patients by lesion location and compared their performance on the IAT with that of healthy volunteers. Compared to controls, patients with lesions in either the vmPFC or the superior aTL showed increased stereotypical attitudes, whereas patients with lesions in the vlPFC showed decreased stereotypical attitudes. The functional contributions of these regions in social attitudes are discussed.     

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.     

The effects of high frequency rTMS on negative attentional bias are influenced by baseline state anxiety

High frequency (HF) repetitive Transcranial Magnetic Stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been shown to induce an attentional bias towards threatening information in healthy adults, associated with decreased activation in the right DLPFC and increased activation in the right amygdala. Additionally, it has been shown that healthy individuals with higher state anxiety portray similar negative attentional biases and cortico-subcortical activation patterns to those induced by HF-rTMS of the right DLPFC. Therefore, the aim of this study is to investigate whether inter-individual differences in state anxiety levels prior to the administration of HF-rTMS of the right DLPFC might be related to the degree to which rTMS induces such a negative attentional bias in healthy volunteers. We administered HF-rTMS of the right DLPFC to a group of 28 healthy female individuals. In line with previous research, a single session of HF-rTMS of the right DLPFC induced an attentional bias towards threatening information. Moreover, self-report measures of state anxiety (STAI-State) prior to stimulation correlated positively with the magnitude of the induced attentional bias. More specifically, we found that healthy individuals who scored higher on self-reports of state anxiety acquired more attentional bias towards negative information after HF-rTMS. Therefore, the effects of a single placebo-controlled rTMS session of the right DLPFC is consistent with the effects of a disrupted prefrontal-amygdala circuitry. The effects on attentional bias are largest in those participants reporting higher state anxiety scores, possibly because underlying amygdala activation is highest.     

Neural networks of response shifting: influence of task speed and stimulus material

Functional magnetic resonance imaging (fMRI) was used in 14 healthy subjects to measure brain activation, while response shifting was performed. In the activation phase, subjects were asked to shift their attention between two different types of visually presented stimuli. In the baseline phase, subjects were required to attend to one stimulus type only. Subjects responded by pressing a left or right key according to the side of presentation of the target stimuli. In a verbal task, subjects were required to switch between letters and numbers. In a figural task, subjects reacted to round and square shapes. Stimuli were presented for 750 or 1500 ms. Response shifting revealed significantly increased activation compared to non-switching in the bilateral superior parietal cortex, right occipital cortex, left inferior frontal cortex, left and right striatum, and bilateral dorsolateral prefrontal cortex (DLPFC). Superior parietal and occipital cortex activation may be due to spatial analysis during response shifting. Subvocal rehearsal of the task instructions may have led to activation in the left inferior frontal cortex. Activation in the striatum was related to prefrontal activation and may represent the association between basal ganglia and prefrontal activation during executive control. However, the most important brain region involved in the execution of response shifting was the bilateral DLPFC. Higher task speed increased executive top-down attentional control and, therefore, significantly increased activity in the bilateral DLPFC. Brain activation did not differ significantly between verbal and figural stimulus material. This result suggests that brain activation in the present study illustrates the brain regions involved in the basic cognitive mechanisms of response shifting.     

Short Term Exposure to a Violent Video Game Induces Changes in Frontolimbic Circuitry in Adolescents

Despite evidence of effects of violent video game play on behavior, the underlying neuronal mechanisms involved in these effects remain poorly understood. We report a functional MRI (fMRI) study during two modified Stroop tasks performed immediately after playing a violent or nonviolent video game. Compared with the violent video game group, the nonviolent video game group demonstrated more activation in some regions of the prefrontal cortex during the Counting Stroop task. In contrast to the violent video game group, significantly stronger functional connectivity between left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) was identified in the nonviolent video game group. During an Emotional Stroop task, the violent video game group showed more activity in the right amygdala and less activation in regions of the medial prefrontal cortex (MPFC). Furthermore, functional connectivity analysis revealed the negative coupling between right amygdala and MPFC in the nonviolent video game group. By contrast, no significant functional connectivity between right amygdala and MPFC was found in the violent video game group. These results suggest differential engagement of neural circuitry in response to short term exposure to a violent video game as compared to a nonviolent video game.     

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.