Hauke R. Heekeren

The neural systems that mediate human perceptual decision making

Perceptual decision making is the act of choosing one option or course of action from a set of alternatives on the basis of available sensory evidence. Thus, when we make such decisions, sensory information must be interpreted and translated into behaviour. Neurophysiological work in monkeys performing sensory discriminations, combined with computational modelling, has paved the way for neuroimaging studies that are aimed at understanding decision-related processes in the human brain. Here we review findings from human neuroimaging studies in conjunction with data analysis methods that can directly link decisions and signals in the human brain on a trial-by-trial basis. This leads to a new view about the neural basis of human perceptual decision-making processes.

A general mechanism for perceptual decision-making in the human brain

Findings from single-cell recording studies suggest that a comparison of the outputs of different pools of selectively tuned lower-level sensory neurons may be a general mechanism by which higher-level brain regions compute perceptual decisions. For example, when monkeys must decide whether a noisy field of dots is moving upward or downward, a decision can be formed by computing the difference in responses between lower-level neurons sensitive to upward motion and those sensitive to downward motion. Here we use functional magnetic resonance imaging and a categorization task in which subjects decide whether an image presented is a face or a house to test whether a similar mechanism is also at work for more complex decisions in the human brain and, if so, where in the brain this computation might be performed. Activity within the left dorsolateral prefrontal cortex is greater during easy decisions than during difficult decisions, covaries with the difference signal between face- and house-selective regions in the ventral temporal cortex, and predicts behavioural performance in the categorization task. These findings show that even for complex object categories, the comparison of the outputs of different pools of selectively tuned neurons could be a general mechanism by which the human brain computes perceptual decisions.

Human aging magnifies genetic effects on executive functioning and working memory

We demonstrate that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. We assess two common Val/Met polymorphisms, one affecting the Catechol-O-Methyltransferase (COMT) enzyme, which degrades dopamine (DA) in prefrontal cortex (PFC), and the other influencing the brain-derived neurotrophic factor (BDNF) protein. In two tasks (Wisconsin Card Sorting and spatial working memory), we find that effects of COMT genotype on cognitive performance are magnified in old age and modulated by BDNF genotype. Older COMT Val homozygotes showed particularly low levels of performance if they were also BDNF Met carriers. The age-associated magnification of COMT gene effects provides novel information on the inverted U-shaped relation linking dopaminergic neuromodulation in PFC to cognitive performance. The modulation of COMT effects by BDNF extends recent evidence of close interactions between frontal and medial-temporal circuitries in executive functioning and working memory.

Age-related differences in white matter microstructure: Region-specific patterns of diffusivity

We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

Neural Processing of Risk

In our everyday life, we often have to make decisions with risky consequences, such as choosing a restaurant for dinner or choosing a form of retirement saving. To date, however, little is known about how the brain processes risk. Recent conceptualizations of risky decision making highlight that it is generally associated with emotions but do not specify how emotions are implicated in risk processing. Moreover, little is known about risk processing in non-choice situations and how potential losses influence risk processing. Here we used quantitative meta-analyses of functional magnetic resonance imaging experiments on risk processing in the brain to investigate (1) how risk processing is influenced by emotions, (2) how it differs between choice and non-choice situations, and (3) how it changes when losses are possible. By showing that, over a range of experiments and paradigms, risk is consistently represented in the anterior insula, a brain region known to process aversive emotions such as anxiety, disappointment, or regret, we provide evidence that risk processing is influenced by emotions. Furthermore, our results show risk-related activity in the dorsolateral prefrontal cortex and the parietal cortex in choice situations but not in situations in which no choice is involved or a choice has already been made. The anterior insula was predominantly active in the presence of potential losses, indicating that potential losses modulate risk processing.

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.

Age-related decline in brain resources modulates genetic effects on cognitive functioning

Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging. Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008), who reported that the effects of the Catechol-O-Methyltransferase (COMT) gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF) gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed. (150 of 150 words)

Genetic variation in dopaminergic neuromodulation influences the ability to rapidly and flexibly adapt decisions

The ability to rapidly and flexibly adapt decisions to available rewards is crucial for survival in dynamic environments. Reward-based decisions are guided by reward expectations that are updated based on prediction errors, and processing of these errors involves dopaminergic neuromodulation in the striatum. To test the hypothesis that the COMT gene Val158Met polymorphism leads to interindividual differences in reward-based learning, we used the neuromodulatory role of dopamine in signaling prediction errors. We show a behavioral advantage for the phylogenetically ancestral Val/Val genotype in an instrumental reversal learning task that requires rapid and flexible adaptation of decisions to changing reward contingencies in a dynamic environment. Implementing a reinforcement learning model with a dynamic learning rate to estimate prediction error and learning rate for each trial, we discovered that a higher and more flexible learning rate underlies the advantage of the Val/Val genotype. Model-based fMRI analysis revealed that greater and more differentiated striatal fMRI responses to prediction errors reflect this advantage on the neurobiological level. Learning rate-dependent changes in effective connectivity between the striatum and prefrontal cortex were greater in the Val/Val than Met/Met genotype, suggesting that the advantage results from a downstream effect of the prefrontal cortex that is presumably mediated by differences in dopamine metabolism. These results show a critical role of dopamine in processing the weight a particular prediction error has on the expectation updating for the next decision, thereby providing important insights into neurobiological mechanisms underlying the ability to rapidly and flexibly adapt decisions to changing reward contingencies.

Performance level modulates adult age differences in brain activation during spatial working memory

Working memory (WM) shows pronounced age-related decline. Functional magnetic resonance imaging (fMRI) studies have revealed age differences in task-related brain activation. Evidence based primarily on episodic memory studies suggests that brain activation patterns can be modulated by task difficulty in both younger and older adults. In most fMRI aging studies on WM, however, performance level has not been considered, so that age differences in activation patterns are confounded with age differences in performance level. Here, we address this issue by comparing younger and older low and high performers in an event-related fMRI study. Thirty younger (20–30 years) and 30 older (60–70 years) healthy adults were tested with a spatial WM task with three load levels. A region-of-interest analysis revealed marked differences in the activation patterns between high and low performers in both age groups. Critically, among the older adults, a more “youth-like” load-dependent modulation of the blood oxygen level-dependent signal was associated with higher levels of spatial WM performance. These findings underscore the need of taking performance level into account when studying changes in functional brain activation patterns from early to late adulthood.

Social cognition in borderline personality disorder: evidence for disturbed recognition of the emotions, thoughts, and intentions of others

Disturbed relatedness is a core feature of borderline personality disorder (BPD), and impaired social cognition or deficits in “mentalization” are hypothesized to underlie this feature. To date, only weak empirical evidence argues for impairment in the recognition of emotions, thoughts, or intentions in BPD. Data from facial emotion recognition research indicate that these abilities are altered in BPD only if tasks are complex. The present study aims to assess social cognitive abilities in BPD. Sixty-four women with BPD and 38 healthy controls watched the “Movie for the Assessment of Social Cognition” (MASC), a newly developed film displaying social interactions, and asking for an assessment of the intentions, emotions, and thoughts of the characters. In addition, participants completed an established but less ecologically valid measure of social cognition (“Reading the Mind in the Eyes”; RME). In the RME task, BPD patients did not display impairment in social cognition compared to healthy controls. By contrast, on the more sensitive MASC, women with BPD showed significantly impaired abilities in social cognition compared to healthy controls in their recognition of emotions, thoughts, and intentions. Comorbid PTSD, intrusions, and sexual trauma negatively predicted social cognitive abilities on the more sensitive MASC. Thus, our results suggest impaired social cognitive abilities in BPD. Especially for comorbid PTSD, intrusive symptoms, and history of sexual trauma predicted poor outcomes on social cognition tasks.