H.E.M. den Ouden

Ten simple rules for dynamic causal modeling.

Dynamic causal modeling (DCM) is a generic Bayesian framework for inferring hidden neuronal states from measurements of brain activity. It provides posterior estimates of neurobiologically interpretable quantities such as the effective strength of synaptic connections among neuronal populations and their context-dependent modulation. DCM is increasingly used in the analysis of a wide range of neuroimaging and electrophysiological data. Given the relative complexity of DCM, compared to conventional analysis techniques, a good knowledge of its theoretical foundations is needed to avoid pitfalls in its application and interpretation of results. By providing good practice recommendations for DCM, in the form of ten simple rules, we hope that this article serves as a helpful tutorial for the growing community of DCM users.

Thinking about intentions

In this fMRI study, we investigated the convergence of underlying neural networks in thinking about a scenario involving ones own intentional action and its consequences and setting up and holding in mind an intention to act. A factorial design was employed comprising two factors: i. Causality (intentional or physical events) and ii. Prospective Memory (present or absent). In each condition, subjects answered questions about various hypothetical scenarios, which related either to the link between the subjects own intentions and consequential actions (Intentional Causality) or to the link between a natural, physical event and its consequences (Physical Causality). A prospective memory task was embedded in half the blocks. In this task, subjects were required to keep in mind an intention (to press a key on seeing a red stimulus background) whilst carrying out the ongoing Causality task. Answering questions about intentional causality versus physical causality activated a network of regions that have traditionally been associated with Theory of Mind, including the medial prefrontal cortex (mPFC), the superior temporal sulcus and the temporal poles bilaterally. In addition, the precuneus bordering with posterior cingulate cortex, an area involved in self-awareness and self-related processing, was activated more when thinking about intentional causality. In the prospective memory task, activations were found in the right parietal cortex, frontopolar cortex (BA 10) and precuneus. Different subregions within the precuneus/posterior cingulate cortex were activated in both main effects of intentional causality and prospective memory. Therefore, the precuneus/posterior cingulate cortex subserves separately thinking about ones own intentions and consequent actions and bearing in mind an intention to make an action. Previous studies have shown that prospective memory, requiring the formation of an intention and the execution of a corresponding action, is associated with decreased activation in the dorsal mPFC, close to the region activated in Theory of Mind tasks. Here, we found that holding in mind an intention to act and at the same time thinking about an intentional action led to reduced activity in a dorsal section of the mPFC. This was a different region from a more anterior, inferior dorsal mPFC region that responded to intentional causality. This suggests that different regions of mPFC play different roles in thinking about intentions.

Striatal Prediction Error Modulates Cortical Coupling

Both perceptual inference and motor responses are shaped by learned probabilities. For example, stimulus-induced responses in sensory cortices and preparatory activity in premotor cortex reflect how (un)expected a stimulus is. This is in accordance with predictive coding accounts of brain function, which posit a fundamental role of prediction errors for learning and adaptive behavior. We used functional magnetic resonance imaging and recent advances in computational modeling to investigate how (failures of) learned predictions about visual stimuli influence subsequent motor responses. Healthy volunteers discriminated visual stimuli that were differentially predicted by auditory cues. Critically, the predictive strengths of cues varied over time, requiring subjects to continuously update estimates of stimulus probabilities. This online inference, modeled using a hierarchical Bayesian learner, was reflected behaviorally: speed and accuracy of motor responses increased significantly with predictability of the stimuli. We used nonlinear dynamic causal modeling to demonstrate that striatal prediction errors are used to tune functional coupling in cortical networks during learning. Specifically, the degree of striatal trial-by-trial prediction error activity controls the efficacy of visuomotor connections and thus the influence of surprising stimuli on premotor activity. This finding substantially advances our understanding of striatal function and provides direct empirical evidence for formal learning theories that posit a central role for prediction error-dependent plasticity.

Do patients with schizophrenia exhibit aberrant salience

Background It has been suggested that some psychotic symptoms reflect ‘aberrant salience’, related to dysfunctional reward learning. To test this hypothesis we investigated whether patients with schizophrenia showed impaired learning of task-relevant stimulus–reinforcement associations in the presence of distracting task-irrelevant cues. Method We tested 20 medicated patients with schizophrenia and 17 controls on a reaction time game, the Salience Attribution Test. In this game, participants made a speeded response to earn money in the presence of conditioned stimuli (CSs). Each CS comprised two visual dimensions, colour and form. Probability of reinforcement varied over one of these dimensions (task-relevant), but not the other (task-irrelevant). Measures of adaptive and aberrant motivational salience were calculated on the basis of latency and subjective reinforcement probability rating differences over the task-relevant and task-irrelevant dimensions respectively. Results Participants rated reinforcement significantly more likely and responded significantly faster on high-probability-reinforced relative to low-probability-reinforced trials, representing adaptive motivational salience. Patients exhibited reduced adaptive salience relative to controls, but the two groups did not differ in terms of aberrant salience. Patients with delusions exhibited significantly greater aberrant salience than those without delusions, and aberrant salience also correlated with negative symptoms. In the controls, aberrant salience correlated significantly with ‘introvertive anhedonia’ schizotypy. Conclusions These data support the hypothesis that aberrant salience is related to the presence of delusions in medicated patients with schizophrenia, but are also suggestive of a link with negative symptoms. The relationship between aberrant salience and psychotic symptoms warrants further investigation in unmedicated patients.

The Human Basal Ganglia Modulate Frontal-Posterior Connectivity during Attention Shifting

Current models of flexible cognitive control emphasize the role of the prefrontal cortex. This region has been shown to control attention by biasing information processing in favor of task-relevant representations. However, the prefrontal cortex does not act in isolation. We used functional magnetic resonance imaging combined with nonlinear dynamic causal modeling to demonstrate that the basal ganglia play a role in modulating the top-down influence of the prefrontal cortex on visual processing in humans. Specifically, our results reveal that connectivity between the prefrontal cortex and stimulus-specific visual association areas depends on activity in the ventral striatopallidum, elicited by salient events leading to shifts in attention. These data integrate disparate literatures on top-down control by the prefrontal cortex and selective gating by the basal ganglia and highlight the importance of the basal ganglia for high-level cognitive control.

Converging evidence for central 5-HT effects in acute tryptophan depletion.

Acute tryptophan depletion (ATD), a dietary technique for manipulating brain serotonin (5-HT) function, has advanced our understanding of 5-HT mechanisms in the etiology and treatment of depression and other affective disorders.1 A recent review article in Molecular Psychiatry questioned the validity of ATD.2 Although we agree that ATDs effects on 5-HT activity at the molecular level need further clarification, van Donkelaar et al.2 goes too far in challenging whether ATD exerts its effects through serotonergic mechanisms. There is strong evidence that ATD reduces brain 5-HT and disrupts stimulated 5-HT release,3, 4 and converging translational findings support a central role for brain 5-HT in ATDs effects on cognition and behavior.

Reduced Serotonin Transporter Availability Decreases Prefrontal Control of the Amygdala

After a threatening event, the risk of developing social psychopathologies is increased in short-allele (s) carriers of the serotonin transporter gene. The amygdala becomes overresponsive to emotional stimuli, an effect that could be driven by local hypersensitivity or by reduced prefrontal regulation. This study distinguishes between these two hypotheses by using dynamic causal modeling of fMRI data acquired in a preselected cohort of human s-carriers and homozygous long-allele carriers. Increased amygdala activity in s-carriers originates from reduced prefrontal inhibitory regulation when social emotional behavior needs to be controlled, suggesting a mechanism for increased vulnerability to psychopathologies.

Colour helps to solve the binocular matching problem

The spatial differences between the two retinal images, called binocular disparities, can be used to recover the three‐dimensional (3D) aspects of a scene. The computation of disparity depends upon the correct identification of corresponding features in the two images. Understanding what image features are used by the brain to solve this binocular matching problem is an important issue in research on stereoscopic vision. The role of colour in binocular vision is controversial and it has been argued that colour is ineffective in achieving binocular vision. In the current experiment subjects were required to indicate the amount of perceived depth. The stimulus consisted of an array of fronto‐parallel bars uniformly distributed in a constant sized volume. We studied the perceived depth in those 3D stimuli by manipulating both colour (monochrome, trichrome) and luminance (congruent, incongruent). Our results demonstrate that the amount of perceived depth was influenced by colour, indicating that the visual system uses colour to achieve binocular matching. Physiological data have revealed cortical cells in macaque V2 that are tuned both to binocular disparity and to colour. We suggest that one of the functional roles of these cells may be to help solve the binocular matching problem.

The Cerebral Network of Parkinson's Tremor: An Effective Connectivity fMRI Study

UNLABELLED Parkinsons resting tremor has been linked to pathophysiological changes both in the basal ganglia and in a cerebello-thalamo-cortical motor loop, but the role of those circuits in initiating and maintaining tremor remains unclear. Here, we test whether and how the cerebello-thalamo-cortical loop is driven into a tremor-related state by virtue of its connectivity with the basal ganglia. An internal replication design on two independent cohorts of tremor-dominant Parkinson patients sampled brain activity and tremor with concurrent EMG-fMRI. Using dynamic causal modeling, we tested: (1) whether activity at the onset of tremor episodes drives tremulous network activity through the basal ganglia or the cerebello-thalamo-cortical loop and (2) whether the basal ganglia influence the cerebello-thalamo-cortical loop through connectivity with the cerebellum or motor cortex. We compared five physiologically plausible circuits, model families in which transient activity at the onset of tremor episodes (assessed using EMG) drove network activity through the internal globus pallidus (GPi), external globus pallidus, motor cortex, thalamus, or cerebellum. In each family, we compared two models in which the basal ganglia and cerebello-thalamo-cortical loop were connected through the cerebellum or motor cortex. In both cohorts, cerebral activity associated with changes in tremor amplitude (using peripheral EMG measures as a proxy for tremor-related neuronal activity) drove network activity through the GPi, which effectively influenced the cerebello-thalamo-cortical loop through the motor cortex. We conclude that cerebral activity related to Parkinsons tremor first arises in the GPi and is then propagated to the cerebello-thalamo-cortical circuit. SIGNIFICANCE STATEMENT Parkinsons resting tremor has been linked to pathophysiological changes both in the basal ganglia and in a cerebello-thalamo-cortical motor loop, but the role of those circuits in initiating and maintaining tremor remains unclear. Using dynamic causal modeling of concurrently collected EMG-fMRI data in two cohorts of Parkinsons patients, we showed that cerebral activity associated with changes in tremor amplitude drives network activity through the basal ganglia. Furthermore, the basal ganglia effectively influenced the cerebello-thalamo-cortical circuit through the motor cortex (but not the cerebellum). Out findings suggest that Parkinsons tremor-related activity first arises in the basal ganglia and is then propagated to the cerebello-thalamo-cortical circuit.

Gambling Rats and Gambling Addiction: Reconciling the Role of Dopamine in Irrationality

Pathological gambling is a behavioral addiction that is characterized by excessive (monetary) risk-taking in the face of negative consequences, like bankruptcy or relationship problems. Brain dopamine has been suggested to play an important role in both risky behaviors and gambling addiction. Yet,