Anteroventral Prefrontal Cortex Research Articles

Cortical activation abnormalities in bipolar and schizophrenia patients in a combined oddball\u2013incongruence paradigm

Patients with bipolar disorder and schizophrenia often suffer from severe cognitive impairment even during times of remission. This study investigated the pathomechanisms underlying their deficits in cognitive control. A combined oddball–incongruence fMRI task was applied to examine similarities and differences of neural activation patterns between patients and healthy controls. Bipolar and schizophrenia patients demonstrated hyperactivations in the intraparietal cortex during the oddball condition. Furthermore, bipolar patients revealed diagnosis-specific hyperactivation in the left middle frontal gyrus, precentral gyrus, anteroventral prefrontal cortex and orbitofrontal cortex regions compared to schizophrenia patients and healthy individuals. In comparison to healthy controls the patients showed hypoactivations in the inferior frontal junction and ventral pathway during the cognitively more demanding incongruence. Taken together, bipolar patients seem to recruit frontal and parietal areas during the oddball condition to compensate for potential deficits in their attentional network. During more challenging tasks, i.e., the incongruence condition, their compensatory mechanisms seem to collapse leading to hypoactivations in the same frontal areas as well as the ventral pathway.

Resilience to adversity is associated with increased activity and connectivity in the VTA and hippocampus.

Accumulating evidence suggests altered function of the mesolimbic reward system resulting from exposure to early adversity. The present study investigated the combined long-term impact of adversity until young adulthood on neuronal reward processing and its interaction with individual resilience processes. In this functional magnetic resonance imaging study, 97 healthy young adults performed a reward-based decision-making task. Adversity as well as resilience were assessed retrospectively using the validated childhood trauma questionnaire, trauma history questionnaire and a resilience scale. Subjects with high adversity load showed reduced reward-related bottom-up activation in the ventral striatum (VS), ventral tegmental area (VTA) and hippocampus (HP) as compared to the low adversity group. However, high resilience traits in individuals with high adversity load were associated with an increased activation in the VTA and HP, indicating a possible resilience-related protective mechanism. Moreover, when comparing groups with high to low adversity, psychophysiological interaction analyses highlighted an increased negative functional coupling between VS and VTA as well as between VS and anteroventral prefrontal cortex (avPFC) during reward acceptance, and an impaired top-down control of the VS by the avPFC during reward rejection. In turn, combination of high adversity and high resilience traits was associated with an improved functional coupling between VTA, VS and HP. Thereby, the present findings identify neural mechanisms mediating interacting effects of adversity and resilience, which could be targeted by early intervention and prevention.

Altered neural responsivity to food cues in relation to food preferences, but not appetite-related hormone concentrations after RYGB-surgery

BackgroundAfter Roux-en-Y gastric bypass (RYGB) surgery, patients report a shift in food preferences away from high-energy foods. ObjectiveWe aimed to elucidate the potential mechanisms underlying this shift in food preferences by assessing changes in neural responses to food pictures and odors before and after RYGB. Additionally, we investigated whether altered neural responsivity was associated with changes in plasma endocannabinoid and ghrelin concentrations. Design19 RYGB patients (4 men; age 41 ± 10 years; BMI 41 ± 1 kg/m2 before; BMI 36 ± 1 kg/m2 after) participated in this study. Before and two months after RYGB surgery, they rated their food preferences using the Macronutrient and Taste Preference Ranking Task and BOLD fMRI responses towards pictures and odors of high-, and low-energy foods and non-food items were measured. Blood samples were taken to determine plasma endocannabinoid and ghrelin concentrations pre- and post-surgery. ResultsPatients demonstrated a shift in food preferences away from high-fat/sweet and towards low-energy/savory food products, which correlated with decreased superior parietal lobule responsivity to high-energy food odor and a reduced difference in precuneus responsivity to high-energy versus low-energy food pictures. In the anteroventral prefrontal cortex (superior frontal gyrus) the difference in deactivation towards high-energy versus non-food odors reduced. The precuneus was less deactivated in response to all cues. Plasma concentrations of anandamide were higher after surgery, while plasma concentrations of other endocannabinoids and ghrelin did not change. Alterations in appetite-related hormone concentrations did not correlate with changes in neural responsivity. ConclusionsRYGB leads to changed responsivity of the frontoparietal control network that orchestrates top-down control to high-energy food compared to low-energy food and non-food cues, rather than in reward related brain regions, in a satiated state. Together with correlations with the shift in food preference from high- to low-energy foods this indicates a possible role in new food preference formation.

Hyperresponsivity and impaired prefrontal control of the mesolimbic reward system in schizophrenia

Schizophrenia is characterized by substantial dysfunctions of reward processing, leading to detrimental consequences for decision-making. The neurotransmitter dopamine is responsible for the transmission of reward signals and also known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), sixteen medicated patients with schizophrenia and sixteen healthy controls performed the ‘desire-reason dilemma’ (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom–up and top–down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Both patients and controls showed significant activations in the mesolimbic reward system. In patients with schizophrenia, however, we found a significant hyperactivation of the left ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top–down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide evidence for an increased ventral striatal activation to reward stimuli and an impaired top–down control of reward signals by prefrontal brain regions in schizophrenia.

Hyperresponsivity and impaired prefrontal control of the mesolimbic reward system in schizophrenia

Using functional magnetic resonance imaging (fMRI), sixteen medicated schizophrenic patients and sixteen healthy controls performed the ‘desire-reason dilemma’ (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom-up and top-down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Patients with schizophrenia and healthy controls showed significant activations in the dopaminergic reward system. In schizophrenic patients, however, we found a significant hyperactivation of the ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top-down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide further evidence for a hyperresponsivity of the dopaminergic reward system to reward stimuli and an impaired top-down control of reward signals by prefrontal brain regions in schizophrenia.

Disturbed Anterior Prefrontal Control of the Mesolimbic Reward System and Increased Impulsivity in Bipolar Disorder

Bipolar disorder (BD) is characterized by recurrent mood episodes ranging from severe depression to acute full-blown mania. Both states of this severe psychiatric disorder have been associated with alterations of reward processing in the brain. Here, we present results of a functional magnetic resonance imaging (fMRI) study on the neural correlates and functional interactions underlying reward gain processing and reward dismissal in favor of a long-term goal in bipolar patients. Sixteen medicated patients diagnosed with bipolar I disorder, euthymic to mildly depressed, and sixteen matched healthy controls performed the 'desire-reason dilemma' (DRD) paradigm demanding rejection of priorly conditioned reward stimuli to successfully pursue a superordinate goal. Both groups exhibited significant activations in reward-related brain regions, particularly in the mesolimbic reward system. However, bipolar patients showed reduced neural responses of the ventral striatum (vStr) when exploiting a reward stimulus, and exhibited a decreased suppression of the reward-related activation of the mesolimbic reward system while having to reject immediate reward in favor of the long-term goal. Further, functional interaction between the anteroventral prefrontal cortex and the vStr in the 'DRD' was significantly impaired in the bipolar group. These findings provide evidence for a reduced responsivity of the vStr to reward stimuli in BD, possibly related to clinical features like anhedonia. The disturbed top-down control of mesolimbic reward signals by prefrontal brain regions in BD can be interpreted in terms of a disease-related enhanced impulsivity, a trait marker of BD.

A functional neuroimaging study assessing gender differences in the neural mechanisms underlying the ability to resist impulsive desires

There is ample evidence of gender differences in neural processes and behavior. Differences in reward-related behaviors have been linked to either temporary or permanent organizational influences of gonadal hormones on the mesolimbic dopamine system and reward-related activation. Still, little is known about the association between biological gender and the neural underpinnings of the ability to resist reward-related impulses. Here we assessed with functional magnetic resonance imaging which neural processes enable men and women to successfully control their desire for immediate reward when this is required by a higher-order goal (i.e., during a ‘desire-reason dilemma’; Diekhof and Gruber, 2010). Thirty-two participants (16 females) were closely matched for age, personality characteristics (e.g., novelty seeking) and behavioral performance in the ‘desire-reason task’. On the neural level, men and women showed similarities in the general response of the nucleus accumbens and of the ventral tegmental area to predictors of immediate reward, but they differed in additional brain mechanisms that enabled self-controlled decisions against the preference for immediate reward. Firstly, men exhibited a stronger reduction of activation in the ventral pallidum, putamen, temporal pole and pregenual anterior cingulate cortex during the ‘desire-reason dilemma’. Secondly, connectivity analyses revealed a significant change in the direction of the connectivity between anteroventral prefrontal cortex and nucleus accumbens during decisions counteracting the reward-related impulse when comparing men and women. Together, these findings support the view of a sexual dimorphism that manifested in the recruitment of gender-specific neural resources during the successful deployment of self-control.

Modulation of Frontostriatal Interaction Aligns with Reduced Primary Reward Processing under Serotonergic Drugs

Recently, functional interactions between anteroventral prefrontal cortex and nucleus accumbens (NAcc) have been shown to relate to behavior counteracting reward-desiring (Diekhof and Gruber, 2010). Downregulation of the reward system by serotonin has also been suggested as the mode of action accounting for unsatisfactory effects of serotonin reuptake inhibitors (SSRIs) such as insufficient alleviation or even increase of anhedonia, and loss of interest. However, understanding of the in vivo mechanisms of SSRI-related alteration of the human reward system is still incomplete. Using functional magnetic resonance imaging (fMRI) within a double-blind cross-over within-subjects study design and administering the SSRI paroxetine, the dopamine/norepinephrine reuptake inhibitor bupropione, and placebo for 7 d each, we investigated a group of 18 healthy male subjects. Under paroxetine, subjects showed significantly decreased activation of the bilateral NAcc during processing of primary rewards (erotic videos), but not under bupropion. Similar to the previous study, analysis of psychophysiological interactions revealed that this downregulation relied on negative interactions between left and right NAcc fMRI signals and the bilateral anteroventral prefrontal cortex that now were significantly enhanced under paroxetine and reduced under bupropion. Individual drug-dependent modulations of interacting brain regions were significantly associated with individual expressions of impulsivity as a personality trait. Our results corroborate and extend previous insights on interregional crosstalk from secondary to primary rewards and demonstrate parallels between active inhibitory control of and serotonergic effects on the dopaminergic reward system's activity.

Impulsive personality and the ability to resist immediate reward: An fMRI study examining interindividual differences in the neural mechanisms underlying self‐control

The ability to resist immediate rewards is crucial for lifetime success and individual well-being. Using functional magnetic resonance imaging, we assessed the association between trait impulsivity and the neural underpinnings of the ability to control immediate reward desiring. Low and high extreme impulsivity groups were compared with regard to their behavioral performance and brain activation in situations, in which they had to forego immediate rewards with varying value to achieve a superordinate long-term goal. We found that highly impulsive (HI) individuals, who successfully compensated for their lack in behavioral self-control, engaged two complementary brain mechanisms when choosing actions in favor of a long-term goal, but at the expense of an immediate reward. First, self-controlled decisions led to a general attenuation of reward-related activation in the nucleus accumbens, which was accompanied by an increased inverse connectivity with the anteroventral prefrontal cortex. Second, HI subjects controlled their desire for increasingly valuable, but suboptimal rewards through a linear reduction of activation in the ventromedial prefrontal cortex (VMPFC). This was achieved by an increased inverse coupling between the VMPFC and the ventral striatum. Importantly, the neural mechanisms observed in the HI group differed from those in extremely controlled individuals, despite similar behavioral performance. Collectively, these results suggest trait-specific neural mechanisms that allow HI individuals to control their desire for immediate reward.

When Desire Collides with Reason: Functional Interactions between Anteroventral Prefrontal Cortex and Nucleus Accumbens Underlie the Human Ability to Resist Impulsive Desires

Human decisions are guided by "desire" or "reason," which control actions oriented toward either proximal or long-term goals. Here we used functional magnetic resonance imaging to assess how the human brain mediates the balance between proximal reward desiring and long-term goals, when actions promoting a superordinate goal preclude exploitation of an immediately available reward option. Consistent with the view that the reward system interacts with prefrontal circuits during action control, we found that behavior favoring the long-term goal, but counteracting immediate reward desiring, relied on a negative functional interaction of anteroventral prefrontal cortex (avPFC) with nucleus accumbens (Nacc) and ventral tegmental area. The degree of functional interaction between avPFC and Nacc further predicted behavioral success during pursuit of the distal goal, when confronted with a proximal reward option, and scaled with interindividual differences in trait impulsivity. These findings reveal how the human brain accomplishes voluntary action control guided by "reason," suggesting that inhibitory avPFC influences Nacc activity during actions requiring a restraint of immediate "desires."

When desire collides with reason: functional interactions between anteroventral prefrontal cortex and nucleus accumbens underlie the human ability to resist impulsive desires

When desire collides with reason: functional interactions between anteroventral prefrontal cortex and nucleus accumbens underlie the human ability to resist impulsive desires