Ulrike Basten

How the brain integrates costs and benefits during decision making

When we make decisions, the benefits of an option often need to be weighed against accompanying costs. Little is known, however, about the neural systems underlying such cost–benefit computations. Using functional magnetic resonance imaging and choice modeling, we show that decision making based on cost–benefit comparison can be explained as a stochastic accumulation of cost–benefit difference. Model-driven functional MRI shows that ventromedial and left dorsolateral prefrontal cortex compare costs and benefits by computing the difference between neural signatures of anticipated benefits and costs from the ventral striatum and amygdala, respectively. Moreover, changes in blood oxygen level dependent (BOLD) signal in the bilateral middle intraparietal sulcus reflect the accumulation of the difference signal from ventromedial prefrontal cortex. In sum, we show that a neurophysiological mechanism previously established for perceptual decision making, that is, the difference-based accumulation of evidence, is fundamental also in value-based decisions. The brain, thus, weighs costs against benefits by combining neural benefit and cost signals into a single, difference-based neural representation of net value, which is accumulated over time until the individual decides to accept or reject an option.

Trait anxiety modulates the neural efficiency of inhibitory control

An impairment of attentional control in the face of threat-related distracters is well established for high-anxious individuals. Beyond that, it has been hypothesized that high trait anxiety more generally impairs the neural efficiency of cognitive processes requiring attentional control—even in the absence of threat-related stimuli. Here, we use fMRI to show that trait anxiety indeed modulates brain activation and functional connectivities between task-relevant brain regions in an affectively neutral Stroop task. In high-anxious individuals, dorsolateral pFC showed stronger task-related activation and reduced coupling with posterior lateral frontal regions, dorsal ACC, and a word-sensitive area in the left fusiform gyrus. These results support the assumption that a general (i.e., not threat-specific) impairment of attentional control leads to reduced neural processing efficiency in anxious individuals. The increased dorsolateral pFC activation is interpreted as an attempt to compensate for suboptimal connectivity within the cortical network subserving task performance.

Effects of dopamine-related gene–gene interactions on working memory component processes

Dopamine modulates complex cognitive functions like working memory and cognitive control. It is widely accepted that an optimal level of prefrontal dopamine supports working memory performance. In the present study we used a molecular genetic approach to test whether the optimal activity of the dopamine system for different component processes of working memory is additionally related to the availability of dopamine D2 receptors. We sought evidence for this assumption by investigating the interaction effect (epistasis) of variations in two dopaminergic candidate genes: the catechol‐O‐methyltransferase (COMT) Val158Met polymorphism, which has been shown to influence prefrontal dopamine concentration, and the DRD2/ANKK1‐Taq‐Ia polymorphism, which has been related to the density of D2 receptors. Our results show that COMT effects on working memory performance are modulated by the DRD2/ANKK1‐TAQ‐Ia polymorphism and the specific working memory component process under investigation. Val− participants – supposedly characterized by increased prefrontal dopamine concentrations – outperformed Val+ participants in the manipulation of working memory contents, but only when D2 receptor density could be considered to be high. No such effect was present for passive maintenance of working memory contents or for maintenance in the face of distracting information. This beneficial effect of a balance between prefrontal dopamine availability and D2 receptor density reveals the importance of considering epistasis effects and different working memory subprocesses in genetic association studies.

Epistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met Polymorphism Impacts Novelty Seeking and Harm Avoidance

Mounting evidence from animal studies show that the mesolimbic dopaminergic pathways are modulated by the brain-derived neurotrophic factor (BDNF). This study investigates in N=768 healthy Caucasian participants the influence of two prominent functional single-nucleotide polymorphisms (SNPs) on the BDNF gene (BDNF Val66Met SNP) and the ankyrin repeat and kinase domain containing 1 (ANKK1) gene (DRD2 Taq Ia/ANKK1 SNP) on the personality traits of Novelty Seeking and Harm Avoidance, which are mediated, in part, through dopaminergic mesolimbic circuitry. Carriers of the 66Met+/A1+ variant scored lowest on Novelty Seeking and highest on Harm Avoidance, compared to all other genotype groups. These participants are characterized by a relatively low D2 receptor density in the striatum and an impaired activity-dependent secretion of BDNF. This is one of the first genetic association studies to show a modulatory role for BDNF genetic variation on genetically mediated differences in the mesolimbic dopaminergic system in the context of human personality.

Trait anxiety and the neural efficiency of manipulation in working memory

The present study investigates the effects of trait anxiety on the neural efficiency of working memory component functions (manipulation vs. maintenance) in the absence of threat-related stimuli. For the manipulation of affectively neutral verbal information held in working memory, high- and low-anxious individuals (N = 46) did not differ in their behavioral performance, yet trait anxiety was positively related to the neural effort expended on task processing, as measured by BOLD signal changes in fMRI. Higher levels of anxiety were associated with stronger activation in two regions implicated in the goal-directed control of attention—that is, right dorsolateral prefrontal cortex (DLPFC) and left inferior frontal sulcus—and with stronger deactivation in a region assigned to the brain’s default-mode network—that is, rostral–ventral anterior cingulate cortex. Furthermore, anxiety was associated with a stronger functional coupling of right DLPFC with ventrolateral prefrontal cortex. We interpret our findings as reflecting reduced processing efficiency in high-anxious individuals and point out the need to consider measures of functional integration in addition to measures of regional activation strength when investigating individual differences in neural efficiency. With respect to the functions of working memory, we conclude that anxiety specifically impairs the processing efficiency of (control-demanding) manipulation processes (as opposed to mere maintenance). Notably, this study contributes to an accumulating body of evidence showing that anxiety also affects cognitive processing in the absence of threat-related stimuli.

Prefrontal cortical mechanisms underlying individual differences in cognitive flexibility and stability

The pFC is critical for cognitive flexibility (i.e., our ability to flexibly adjust behavior to changing environmental demands), but also for cognitive stability (i.e., our ability to follow behavioral plans in the face of distraction). Behavioral research suggests that individuals differ in their cognitive flexibility and stability, and neurocomputational theories of working memory relate this variability to the concept of attractor stability in recurrently connected neural networks. We introduce a novel task paradigm to simultaneously assess flexible switching between task rules (cognitive flexibility) and task performance in the presence of irrelevant distractors (cognitive stability) and to furthermore assess the individual “spontaneous switching rate” in response to ambiguous stimuli to quantify the individual dispositional cognitive flexibility in a theoretically motivated way (i.e., as a proxy for attractor stability). Using fMRI in healthy human participants, a common network consisting of parietal and frontal areas was found for task switching and distractor inhibition. More flexible persons showed reduced activation and reduced functional coupling in frontal areas, including the inferior frontal junction, during task switching. Most importantly, the individual spontaneous switching rate antagonistically affected the functional coupling between inferior frontal junction and the superior frontal gyrus during task switching and distractor inhibition, respectively, indicating that individual differences in cognitive flexibility and stability are indeed related to a common prefrontal neural mechanism. We suggest that the concept of attractor stability of prefrontal working memory networks is a meaningful model for individual differences in cognitive stability versus flexibility.

The BDNF Val66Met polymorphism and smoking

Although the brain derived neurotrophic factor (BDNF) has been mainly investigated in the context of depression and anxiety disorders, several studies also suggest an association between BDNF and smoking. BDNF represents a protein which crucially influences several processes in the cell ranging from growth to apoptosis. A functional variant of the BDNF gene - the BDNF Val66Met polymorphism - is one of the main targets in BDNF research because of its influence on BDNF secretion. Recently an association between the 66Met allele and smoking has been reported in a sample of 320 Caucasians. The aim of the present study was to replicate this association in a sample nearly twice as large consisting of N=614 German Caucasian participants. A link between smoking and the BDNF Val66Met polymorphism could not be found in our data.

Functional connectivity separates switching operations in the posterior lateral frontal cortex

Task representations consist of different aspects such as the representations of the relevant stimuli, the abstract rules to be applied, and the actions to be performed. To be flexible in our daily lives, we frequently need to switch between some or all aspects of a task. In the present study, we examined whether switching between abstract task rules and switching between response hands is associated with overlapping regions in the posterior lateral frontal cortex and whether switching between these two aspects of a task representation is neurally implemented by distinct functional brain networks. Subjects performed a cue-based task-switching paradigm where the location of the task cue additionally specified the response hand to be used. Overlapping activity for switching between abstract rules versus response hands was present in the inferior frontal junction area of the posterolateral frontal cortex. This region, however, showed very distinct patterns of functional connectivity depending on the content of the switch: Increased functional connectivity with anterior prefrontal, superior frontal, and hippocampal regions was present for abstract rule switching, whereas response hand switching led to increased coupling with motor regions surrounding the central sulcus. These results reveal that a rather general involvement of the posterior lateral frontal cortex in different switching contexts can be further characterized by highly specific functional interactions with other task-relevant regions, depending on the content of the switch.

The resilience framework as a strategy to combat stress-related disorders

Consistent failure over the past few decades to reduce the high prevalence of stress-related disorders has motivated a search for alternative research strategies. Resilience refers to the phenomenon of many people maintaining mental health despite exposure to psychological or physical adversity. Instead of aiming to understand the pathophysiology of stress-related disorders, resilience research focuses on protective mechanisms that shield people against the development of such disorders and tries to exploit its insights to improve treatment and, in particular, disease prevention. To fully harness the potential of resilience research, a critical appraisal of the current state of the art — in terms of basic concepts and key methods — is needed. We highlight challenges to resilience research and make concrete conceptual and methodological proposals to improve resilience research. Most importantly, we propose to focus research on the dynamic processes of successful adaptation to stressors in prospective longitudinal studies.