Intermittent compared to continuous real-time fMRI neurofeedback boosts control over amygdala activation.

Real-time fMRI neurofeedback is a feasible tool to learn the volitional regulation of brain activity. So far, most studies provide continuous feedback information that is presented upon every volume acquisition. Although this maximizes the temporal resolution of feedback information, it may be accompanied by some disadvantages. Participants can be distracted from the regulation task due to (1) the intrinsic delay of the hemodynamic response and associated feedback and (2) limited cognitive resources available to simultaneously evaluate feedback information and stay engaged with the task. Here, we systematically investigate differences between groups presented with different variants of feedback (continuous vs. intermittent) and a control group receiving no feedback on their ability to regulate amygdala activity using positive memories and feelings. In contrast to the feedback groups, no learning effect was observed in the group without any feedback presentation. The group receiving intermittent feedback exhibited better amygdala regulation performance when compared with the group receiving continuous feedback. Behavioural measurements show that these effects were reflected in differences in task engagement. Overall, we not only demonstrate that the presentation of feedback is a prerequisite to learn volitional control of amygdala activity but also that intermittent feedback is superior to continuous feedback presentation.

General Habit Propensity Relates to the Sensation Seeking Subdomain of Impulsivity But Not Obesity.

According to dual-system theory, instrumental learning and performance depend on the balance between goal-directed and habitual action control. Overreliance on habits has been argued to characterize clinical conditions such as drug addiction or obsessive-compulsive disorder as well as obesity and excessive impulsivity. A tendency toward habitual action control in obesity has already been indicated in the food domain. However, impairments might not be restricted to eating behavior. This has been suggested by domain-general obesity-associated disturbances in executive function as well as alterations in corticostriatal circuits underlying the goal-directed and habitual systems. In this study we examined the balance of goal-directed and habitual action control in a sample of normal-weight, overweight, and obese participants (n = 105) using the slips-of-action test in a non-food context. We tested for continuous or group-based associations between body weight status (BMI) and the devaluation sensitivity index (DSI), a parameter representing the balance of the goal-directed and habitual systems in action control. As personality differences in the domain of impulsivity might affect this relationship, we also examined whether the interaction between BMI and self-reported impulsivity, based on the UPPS Impulsive Behavior Scale, was related to the DSI. In addition to that, we tested for direct, i.e., weight status independent, relationships between UPPS subdomains of impulsivity and the DSI. We failed to find evidence for a relationship between weight status and sensitivity to devaluation as indexed by the DSI. However, independent of weight status, we observed lower sensitivity to devaluation in sensation seekers, a subtype of impulsivity. To conclude, behavioral flexibility in the sense of disturbances in the balance between the habitual and goal-directed systems seems to be unaffected by weight status in a non-food context. Consequently, stimuli and behavior might not be generally excessively linked in overweight or obesity. However, according to ceiling effects we cannot rule out subtle effects the paradigm was not able to disentangle. Further, future studies are needed to clarify the role of specific subtypes of obesity (e.g., food addiction). The indicated habit propensity in sensation seekers may account for previous reports of weak avoidance behavior and risky decision making.

Slips of Action and Sequential Decisions: A Cross-Validation Study of Tasks Assessing Habitual and Goal-Directed Action Control.

Instrumental learning and decision-making rely on two parallel systems: a goal-directed and a habitual system. In the past decade, several paradigms have been developed to study these systems in animals and humans by means of e.g., overtraining, devaluation procedures and sequential decision-making. These different paradigms are thought to measure the same constructs, but cross-validation has rarely been investigated. In this study we compared two widely used paradigms that assess aspects of goal-directed and habitual behavior. We correlated parameters from a two-step sequential decision-making task that assesses model-based (MB) and model-free (MF) learning with a slips-of-action paradigm that assesses the ability to suppress cue-triggered, learnt responses when the outcome has been devalued and is therefore no longer desirable. MB control during the two-step task showed a very moderately positive correlation with goal-directed devaluation sensitivity, whereas MF control did not show any associations. Interestingly, parameter estimates of MB and goal-directed behavior in the two tasks were positively correlated with higher-order cognitive measures (e.g., visual short-term memory). These cognitive measures seemed to (at least partly) mediate the association between MB control during sequential decision-making and goal-directed behavior after instructed devaluation. This study provides moderate support for a common framework to describe the propensity towards goal-directed behavior as measured with two frequently used tasks. However, we have to caution that the amount of shared variance between the goal-directed and MB system in both tasks was rather low, suggesting that each task does also pick up distinct aspects of goal-directed behavior. Further investigation of the commonalities and differences between the MF and habit systems as measured with these, and other, tasks is needed. Also, a follow-up cross-validation on the neural systems driving these constructs across different paradigms would promote the definition and operationalization of measures of instrumental learning and decision-making in humans.

Slave to habit? Obesity is associated with decreased behavioural sensitivity to reward devaluation.

The motivational value of food is lower during satiety compared to fasting. Dynamic changes in motivational value promote food seeking or meal cessation. In obesity this mechanism might be compromised since obese subjects ingest energy beyond homeostatic needs. Thus, lower adaptation of eating behaviour with respect to changes in motivational value might cause food overconsumption in obesity. To test this hypothesis, we implemented a selective satiation procedure to investigate the relationship between obesity and the size of the behavioural devaluation effect in humans. Lean to obese men (mean age 25.9, range 19-30 years; mean BMI 29.1, range 19.2-45.1 kg/m(2)) were trained on a free operant paradigm and learned to associate cues with the possibility to win different food rewards by pressing a button. After the initial training phase, one of the rewards was devalued by consumption. Response rates for and wanting of the different rewards were measured pre and post devaluation. Behavioural sensitivity to reward devaluation, measured as the magnitude of difference between pre and post responses, was regressed against BMI. Results indicate that (1) higher BMI compared to lower BMI in men led to an attenuated behavioural adjustment to reward devaluation, and (2) the decrease in motivational value was associated with the decrease in response rate between pre and post. Change in explicitly reported motivational value, however, was not affected by BMI. Thus, we conclude that high BMI in men is associated with lower behavioural adaptation with respect to changes in motivational value of food, possibly resulting in automatic overeating patterns that are hard to control in daily life.

Body weight status, eating behavior, sensitivity to reward/punishment, and gender: relationships and interdependencies.

Behavioral and personality characteristics are factors that may jointly regulate body weight. This study explored the relationship between body mass index (BMI) and self-reported behavioral and personality measures. These measures included eating behavior (based on the Three-Factor Eating Questionnaire; Stunkard and Messick, 1985), sensitivity to reward and punishment (based on the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales) (Carver and White, 1994) and self-reported impulsivity (based on the Barratt Impulsiveness Scale-11; Patton et al., 1995). We found an inverted U-shaped relationship between restrained eating and BMI. This relationship was moderated by the level of disinhibited eating. Independent of eating behavior, BIS and BAS responsiveness were associated with BMI in a gender-specific manner with negative relationships for men and positive relationships for women. Together, eating behavior and BIS/BAS responsiveness accounted for a substantial proportion of BMI variance (men: ∼25%, women: ∼32%). A direct relationship between self-reported impulsivity and BMI was not observed. In summary, our results demonstrate a system of linear and non-linear relationships between the investigated factors and BMI. Moreover, body weight status was not only associated with eating behavior (cognitive restraint and disinhibition), but also with personality factors not inherently related to an eating context (BIS/BAS). Importantly, these relationships differ between men and women.

Fluorescence resonance energy transfer (FRET) and competing processes in donor-acceptor substituted DNA strands: a comparative study of ensemble and single-molecule data.

We studied the fluorescence resonance energy transfer (FRET) efficiency of different donor-acceptor labeled model DNA systems in aqueous solution from ensemble measurements and at the single molecule level. The donor dyes: tetramethylrhodamine (TMR); rhodamine 6G (R6G); and a carbocyanine dye (Cy3) were covalently attached to the 5'-end of a 40-mer model oligonucleotide. The acceptor dyes, a carbocyanine dye (Cy5), and a rhodamine derivative (JA133) were attached at modified thymidine bases in the complementary DNA strand with donor-acceptor distances of 5, 15, 25 and 35 DNA-bases, respectively. Anisotropy measurements demonstrate that none of the dyes can be observed as a free rotor; especially in the 5-bp constructs the dyes exhibit relatively high anisotropy values. Nevertheless, the dyes change their conformation with respect to the oligonucleotide on a slower time scale in the millisecond range. This results in a dynamic inhomogeneous distribution of donor/acceptor (D/A) distances and orientations. FRET efficiencies have been calculated from donor and acceptor fluorescence intensity as well as from time-resolved fluorescence measurements of the donor fluorescence decay. Dependent on the D/A pair and distance, additional strong fluorescence quenching of the donor is observed, which simulates lower FRET efficiencies at short distances and higher efficiencies at longer distances. On the other hand, spFRET measurements revealed subpopulations that exhibit the expected FRET efficiency, even at short D/A distances. In addition, the measured acceptor fluorescence intensities and lifetimes also partly show fluorescence quenching effects independent of the excitation wavelength, i.e. either directly excited or via FRET. These effects strongly depend on the D/A distance and the dyes used, respectively. The obtained data demonstrate that besides dimerization at short D/A distances, an electron transfer process between the acceptor Cy5 and rhodamine donors has to be taken into account. To explain deviations from FRET theory even at larger D/A distances, we suggest that the pi-stack of the DNA double helix mediates electron transfer from the donor to the acceptor, even over distances as long as 35 base pairs. Our data show that FRET experiments at the single molecule level are rather suited to resolve fluorescent subpopulations in heterogeneous mixture, information about strongly quenched subpopulations gets lost.