The influence of psychological traits and prior experience on treatment expectations.

BACKGROUND: Placebo and nocebo responses are modulated by the treatment expectations of participants and patients. However, interindividual differences predicting treatment expectations and placebo responses are unclear. In this large-scale pooled analysis, we aim to investigate the influence of psychological traits and prior experiences on treatment expectations. METHODS: This paper analyses data from six different placebo studies (total n = 748). In all studies, participants' sociodemographic information, treatment expectations and prior treatment experiences and traits relating to stress, somatization, depression and anxiety, the Big Five and behavioral inhibition and approach tendencies were assessed using the same established questionnaires. Correlation coefficients and structural equation models were calculated to investigate the relationship between trait variables and expectations. RESULTS: We found small positive correlations between side effect expectations and improvement expectations (r = 0.187), perceived stress (r = 0.154), somatization (r = 0.115), agitation (r = 0.108), anhedonia (r = 0.118), and dysthymia (r = 0.118). In the structural equation model previous experiences emerged as the strongest predictors of improvement (ß = 0.32, p = .005), worsening (ß = -0.24, p = .005) and side effect expectations (ß = 0.47, p = .005). Traits related to positive affect (ß = - 0.09; p = .007) and negative affect (ß = 0.04; p = .014) were associated with side effect expectations. DISCUSSION: This study is the first large analysis to investigate the relationship between traits, prior experiences and treatment expectations. Exploratory analyses indicate that experiences of symptom improvement are associated with improvement and worsening expectations, while previous negative experiences are only related to side effect expectations. Additionally, a proneness to experience negative affect may be a predictor for side effect expectation and thus mediate the occurrence of nocebo responses.

Valence Encoding Signals in the Human Amygdala and the Willingness to Eat.

One of the strongest drivers of food consumption is pleasure, and with a large variety of palatable food continuously available, there is rarely any necessity to eat something not tasty. The amygdala is involved in hedonic valuation, but its role in valence assignment during food choices is less understood. Given recent evidence for spatially segregated amygdala signatures encoding palatability, we applied a multivariate approach on fMRI data to extract valence-specific signal patterns during an explicit evaluation of food liking. These valence localizers were then used to identify hedonic valuation processes while the same healthy human participants (14 female, 16 male; in overnight fasted state on both scanning days) performed a willingness-to-eat task in a separate fMRI measurement. Valence-specific patterns of amygdala signaling predicted decisions on food consumption significantly. Findings could be validated using the same valence localizers to predict consumption decisions participants made on a separate set of food stimuli that had not been used for localizer identification. Control analyses revealed these findings to be restricted to a multivariate compared with a univariate approach, and to be specific for valence processing in the amygdala. Spatially distributed valuation signals of the amygdala thus appear to modulate appetitive consumption decisions, and may be useful to identify current hedonic valuation processes triggering food choices even when not explicitly instructed.SIGNIFICANCE STATEMENT The expectation of tastiness is a particularly strong driver in everyday decisions on food consumption. The amygdala is important for hedonic valuation processes and involved in valence-related behavior, but the relationship between both processes is less understood. Here, we show that hedonic values of food are represented in spatially distributed activation patterns in the amygdala. The engagement of these patterns during food choices modulates consumption decisions. Findings are stable in a separate stimulus set. These results suggest that valence-specific amygdala signals are integrated into the formation of food choices.

Rationale and Design of the Hamburg City Health Study.

The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.

Microscopic diffusion anisotropy in the human brain: Age-related changes.

The fractional anisotropy (FA) that can be derived from diffusion tensor imaging (DTI), is ambiguous because it not only depends on the tissue microstructure but also on the axon or fiber orientation distribution within a voxel. Measures of the microscopic diffusion anisotropy, like the microscopic anisotropy index (MA) that can be determined with so-called double-wave-vector (DWV) or double diffusion encoding (DDE) imaging, are independent of this orientation distribution and, thus, offer a more direct and undisguised access to the tissue structure on a cellular or microscopic scale. In this study, FA and MA measurements were performed in a group of aged (>60y), healthy volunteers and compared to the data obtained recently for a group of young (<33y), healthy volunteers to reveal age-related differences. The coefficients-of-variation (CV) determined for the aged group were considerably lower for MA than for FA in average and in most of the 16 ROIs analyzed due to lower between-subject variations of MA. FA differences between the young and the aged group were in line with previous DTI studies. MA was also decreased in the aged group but in more of the 16 ROIs and with a higher significance. Furthermore, MA differences were also observed in frontal brain regions containing fiber crossings that did not reveal significant FA differences, i.e. MA seems to provide a better sensitivity to detect microstructural changes in such regions. In some non-cortical gray matter structures like the putamen, FA was increased but MA was decreased in the aged group which could indicate a coherent fiber orientation in the aged group related to the loss of crossing or fanning fibers. In conclusion, MA not only could improve the detectability of differences of the tissue microstructure but, in conjunction with FA, could also help to identify the underlying changes.

Altered behavioral and neural responsiveness to counterfactual gains in the elderly.

Counterfactual information processing refers to the consideration of events that did not occur in comparison to those actually experienced, in order to determine optimal actions, and can be formulated as computational learning signals, referred to as fictive prediction errors. Decision making and the neural circuitry for counterfactual processing are altered in healthy elderly adults. This experiment investigated age differences in neural systems for decision making with knowledge of counterfactual outcomes. Two groups of healthy adult participants, young (N = 30; ages 19-30 years) and elderly (N = 19; ages 65-80 years), were scanned with fMRI during 240 trials of a strategic sequential investment task in which a particular strategy of differentially weighting counterfactual gains and losses during valuation is associated with more optimal performance. Elderly participants earned significantly less than young adults, differently weighted counterfactual consequences and exploited task knowledge, and exhibited altered activity in a fronto-striatal circuit while making choices, compared to young adults. The degree to which task knowledge was exploited was positively correlated with modulation of neural activity by expected value in the vmPFC for young adults, but not in the elderly. These findings demonstrate that elderly participants' poor task performance may be related to different counterfactual processing.

Microscopic diffusion anisotropy in the human brain: reproducibility, normal values, and comparison with the fractional anisotropy.

Human neuroimaging of tissue microstructure, such as axonal density and integrity, is key in clinical and neuroscience research. Most studies rely on diffusion tensor imaging (DTI) and the measures derived from it, most prominently fractional anisotropy (FA). However, FA also depends on fiber orientation distribution, a more macroscopic tissue property. Recently introduced measures of so-called microscopic diffusion anisotropy, diffusion anisotropy on a cellular or microscopic level, overcome this limitation because they are independent of the orientation distributions of axons and fibers. In this study, we evaluate the feasibility of two measures of microscopic diffusion anisotropy I(MA) and MA indices, for human neuroscience and clinical research. Both indices reflect the eccentricity of the cells but while I(MA) also depends on the cell size, MA is independent of the cell size and, like FA, scaled between 0 and 1. In whole-brain measurements of a group of 19 healthy volunteers, we measured average values and variability, evaluated their reproducibility, both within and between sessions, and compared MA to FA values in selected regions-of-interest (ROIs). The within- and between-session comparison did not show substantial differences but the reproducibility was much better for the MA than I(MA) (coefficient of variation between sessions 10.5% vs. 28.9%). The reproducibility was less for MA than FA overall, but comparable in the defined ROIs and the average group sizes required for between-group comparisons was similar (about 60 participants for a relative difference of 5%). Group-averaged values of MA index were generally larger and showed less variation across white-matter brain ROIs than FA (mean ± standard deviation of seven ROIs 0.83 ± 0.10 vs. 0.58 ± 0.13). Even in some gray-matter ROIs, MA values comparable to those of white matter ROIs were observed. Furthermore, the within-group variation of the values in white matter ROIs was lower for the MA compared to the FA (mean standard deviation over volunteers 0.038 vs. 0.049) which could be due to significant variability in the distribution of fiber orientation contributing to FA. These results indicate that MA (i) should be preferred to I(MA), (ii) has a reproducibility and group-size requirements comparable to those of FA; (iii) is less sensitive to the fiber orientation distribution than FA; and (iv) could be more sensitive to differences or changes of the tissue microstructure than FA. R1.1.

Effects of prospective thinking on intertemporal choice: The role of familiarity.

Imagining future events while performing an intertemporal choice task can attenuate the devaluation of future rewards. Here, we investigated whether this effect and its neural basis depend on the degree of personal prior experience associated with the simulated future scenarios. Functional magnetic resonance imaging was combined with a modified intertemporal choice task in which the delayed options were either purely monetary, or linked with a social event. Subject-specific events differed regarding familiarity, that is, meeting a close, familiar person or a celebrity in a café. In line with recent hypotheses on episodic construction, the simulation of future familiar and unfamiliar events equally attenuated delay discounting behavior in comparison with the control condition and both were imagined with similar richness. Imaging data, however, indicate that these results rely on differential neural activation patterns. The hippocampus was particularly involved in the simulation of unfamiliar future scenarios, probably reflecting enhanced construction processes when personal experience with similar past events is lacking. Consequently, functional coupling of the hippocampus with neural valuation signals in the anterior cingulate cortex predicted the subjective value only of rewards offered in the unfamiliar context. In contrast, valuation of rewards in a familiar context was predicted by activation in key nodes of emotional and autobiographical memory retrieval and dynamically modulated by frontal-striatal connectivity. The present data emphasize that the mechanisms underlying neural valuation of prospective rewards largely depend on the pre-experience with the context in which they are offered.

Sex differences in conditioned stimulus discrimination during context-dependent fear learning and its retrieval in humans: the role of biological sex, contraceptives and menstrual cycle phases.

BACKGROUND: Anxiety disorders are more prevalent in women than in men. Despite this sexual dimorphism, most experimental studies are conducted in male participants and studies focusing on sex differences are sparse. In addition, the role of hormonal contraceptives and menstrual cycle phase in fear conditioning and extinction processes remain largely unknown. METHODS: We investigated sex differences in context-dependent fear acquisition and extinction (day 1) and their retrieval/expression (day 2). Skin conductance responses (SCRs), fear and unconditioned stimulus expectancy ratings were obtained. RESULTS: We included 377 individuals (261 women) in our study. Robust sex differences were observed in all dependent measures. Women generally displayed higher subjective ratings but smaller SCRs than men and showed reduced excitatory/inhibitory conditioned stimulus (CS+/CS-) discrimination in all dependent measures. Furthermore, women using hormonal contraceptives showed reduced SCR CS discrimination on day 2 than men and free-cycling women, while menstrual cycle phase had no effect. LIMITATIONS: Possible limitations include the simultaneous testing of up to 4 participants in cubicles, which might have introduced a social component, and not assessing postexperimental contingency awareness. CONCLUSION: The response pattern in women shows striking similarity to previously reported sex differences in patients with anxiety. Our results suggest that pronounced deficits in associative discrimination learning and subjective expression of safety information (CS- responses) might underlie higher prevalence and higher symptom rates seen in women with anxiety disorders. The data call for consideration of biological sex and hormonal contraceptive use in future studies and may suggest that targeting inhibitory learning during therapy might aid precision medicine.

The need to change: Is there a critical role of midlife adaptation in mental health later in life?

Although late-life depression (LLD) is a serious health problem and more common than dementia in people over 60, it is underdiagnosed and undertreated. The cognitive-emotional etiology of LLD is particularly poorly understood. This is in contrast to the now extensive literature from psychology and cognitive neuroscience on the characteristics of emotionally healthy aging. This research consistently shows a change in emotional processing in older adults that is modulated by prefrontal regulation. Lifespan theories explain this change in terms of neurocognitive adaptation to limited opportunities and resources that typically occur in the second half of life. Epidemiological data on an increase in well-being after a low point around age 50 suggest that the majority of people seem quite capable of making this adaptation, even though empirical evidence for a causal modulation of this so called 'paradox of aging' and for the role of the midlife dip is still lacking. Intriguingly, LLD is associated with deficits in emotional, cognitive, and prefrontal functions similar to those shown to be crucial for healthy adaptation. Suspected causes of these deficits, such as white matter lesions or affective instability, become apparent as early as midlife when internal and external changes as well as daily challenges set in. Based on these findings, we propose that some individuals who develop depression at older ages may not have been able to successfully implement self-regulatory adaptation at midlife. Here, we review the current evidence and theories on successful aging, the neurobiology of LLD, and well-being across the lifespan. Drawing on recent advances in lifespan theories, emotion regulation research, and cognitive neuroscience, we propose a model of successful versus unsuccessful adaptation that emphasizes the increasing need for implicit habitual control and resource-based regulatory choice during midlife.

Expectations and Prior Experiences Associated With Adverse Effects of COVID-19 Vaccination.

Importance: Uptake of vaccination against COVID-19 is strongly affected by concerns about adverse effects. Research on nocebo effects suggests that these concerns can amplify symptom burden. Objective: To investigate whether positive and negative expectations prior to COVID-19 vaccination are associated with systemic adverse effects. Design, Setting, and Participants: This prospective cohort study analyzed the association of expected benefits and risks of vaccination, adverse effects at first vaccination, and observed adverse effects in close contacts with severity of systemic adverse effects among adults receiving a second dose of messenger RNA (mRNA)-based vaccines between August 16 and 28, 2021. A total of 7771 individuals receiving the second dose at a state vaccination center in Hamburg, Germany, were invited to participate; of these, 5370 did not respond, 535 provided incomplete information, and 188 were excluded retrospectively. The mobile application m-Path was used for data collection. Main Outcomes and Measures: Primary outcome was a composite severity index of systemic adverse effects in 12 symptom areas measured once daily with an electronic symptom diary over 7 consecutive days. Data were analyzed by mixed-effects multivariable ordered logistic regression adjusted for prevaccine symptom levels and observation times. Results: A total of 10 447 observations from 1678 individuals receiving vaccinations (BNT162b2 [Pfizer BioNTech] in 1297 [77.3%] and mRNA-1273 [Moderna] in 381 [22.7%]) were collected. The participants' median age was 34 (IQR, 27-44) years, and 862 (51.4%) were women. The risk for more severe adverse effects was higher for persons expecting a lower benefit of vaccination (odds ratio [OR] for higher expectations, 0.72 [95% CI, 0.63-0.83]; P < .001), expecting higher adverse effects of vaccination (OR, 1.39 [95% CI, 1.23-1.58]; P < .001), having experienced higher symptom burden at the first vaccination (OR, 1.60 [95% CI, 1.42-1.82]; P < .001), scoring higher on the Somatosensory Amplification Scale (OR, 1.21 [95% CI, 1.06-1.38]; P = .004), and if the vaccine mRNA-1273 was given rather than BNT162b2 (OR, 2.45 [95% CI, 2.01-2.99]; P < .001). No associations were seen for observed experiences. Conclusions and Relevance: In this cohort study, several nocebo effects occurred in the first week after COVID-19 vaccination. The severity of systemic adverse effects was associated not only with vaccine-specific reactogenicity but also more negative prior experiences with adverse effects from the first COVID-19 vaccination, more negative expectations regarding vaccination, and tendency to catastrophize instead of normalize benign bodily sensations. Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines.

Placebo induced expectations of mood enhancement generate a positivity effect in emotional processing.

A perceptual bias towards negative emotions is a consistent finding in mood disorders and a major target of therapeutic interventions. Placebo responses in antidepressant treatment are substantial, but it is unclear whether and how underlying expectancy effects can modulate response biases to emotional inputs. In a first attempt to approach this question, we investigated how placebo induced expectation can shape the perception of specific emotional stimuli in healthy individuals. In a controlled cross-over design, positive treatment expectations were induced by verbal instructions and a hidden training manipulation combined with an alleged oxytocin nasal spray before participants performed an emotion classification task on happy and fearful facial expressions with varying intensity. Analyses of response criterion and discrimination ability as derived from emotion-specific psychometric functions demonstrate that expectation specifically lowered participants' threshold for identifying happy emotions in general, while they became less sensitive to subtle differences in emotional expressions. These indications of a positivity bias were directly correlated with participants' treatment expectations as well as subjective experiences of treatment effects and went along with a significant mood enhancement. Our findings show that expectations can induce a perceptual positivity effect in healthy individuals which is probably modulated by top-down emotion regulation and which may be able to improve mood state. Clinical implications of these promising results now need to be explored in studies of expectation manipulation in patients with mood disorders.

Insulin sensitivity in mesolimbic pathways predicts and improves with weight loss in older dieters.

Central insulin is critically involved in the regulation of hedonic feeding. Insulin resistance in overweight has recently been shown to reduce the inhibitory function of insulin in the human brain. How this relates to effective weight management is unclear, especially in older people, who are highly vulnerable to hyperinsulinemia and in whom neural target systems of insulin action undergo age-related changes. Here, 50 overweight, non-diabetic older adults participated in a double-blind, placebo-controlled, pharmacological functional magnetic resonance imaging study before and after randomization to a 3-month caloric restriction or active waiting group. Our data show that treatment outcome in dieters can be predicted by baseline measures of individual intranasal insulin (INI) inhibition of value signals in the ventral tegmental area related to sweet food liking as well as, independently, by peripheral insulin sensitivity. At follow-up, both INI inhibition of hedonic value signals in the nucleus accumbens and peripheral insulin sensitivity improved with weight loss. These data highlight the critical role of central insulin function in mesolimbic systems for weight management in humans and directly demonstrate that neural insulin function can be improved by weight loss even in older age, which may be essential for preventing metabolic disorders in later life.

Ventral striatal signal changes represent missed opportunities and predict future choice.

Realizing one has missed an opportunity can influence decision behavior in the future, such that a large missed opportunity leads to more risk taking in the next round. To investigate the neuronal mechanism of this phenomenon we used functional magnetic resonance imaging (fMRI) in combination with a sequential decision task in which the magnitude of possible gains linearly increased, but at the same time the gain probability decreased. After subjects decided to stop a trial and to collect the gains, not only the chosen option (actual outcome), but also the alternative option (maximum possible gain in this round) was revealed. Our data show that a missed chance influenced volunteers' decision behavior: volunteers took more risk after rounds in which they had missed a large opportunity. This was paralleled by signal changes in a lateral area of the ventral striatum that scaled with the difference between what could have been gained and what was actually gained in this round. In addition, after gains signal changes in dopaminoceptive structures including the midbrain and ventral striatum together with the insula predicted individual choice behavior in the subsequent round. Thus, our data provide a neural mechanism for how missed opportunities influence future decisions.

The influence of directed covert attention on emotional face processing.

Activation of the amygdala and the fusiform face area (FFA) are consistent findings in imaging studies on emotional face processing. There is evidence that these activations occur even when emotional faces are unattended; however, it was also shown that amygdala and FFA activation were modulated by the attentional resources allocated to these stimuli. Attentional resources might thereby not only depend on task demands but also on varying degrees of covert attention processes induced by the task. To address this issue we examined the isolated effect of covert shifts of spatial attention on emotional face processing using functional magnetic resonance imaging during a modified spatial cueing paradigm. Directional spatial and neutral cues were presented superimposed on neutral, happy, sad and fearful faces. Subjects performed a target detection task, while fixation was controlled by simultaneous eye tracking. Reaction times showed a strong cue validity effect across all emotions (i.e., faster responses for directional cues). Comparing directed to nondirected attention revealed a significantly reduced signal in the FFA irrespective of the emotional expression. This effect was also seen in bilateral amygdala, but only in trials including fearful faces. Our findings suggest that covert shifts of attention toward a specific location result in reduced face processing independent from task demands. Furthermore, our data show a task-irrelevant amygdala response specific to fearful faces under a wide attentional focus. Attentional disengagement from the faces led to a suppression of this amygdala response and thus provides further evidence that amygdala activation depends on the focus of attention.

Association between FDG uptake, CSF biomarkers and cognitive performance in patients with probable Alzheimer's disease.

PURPOSE: Brain imaging of FDG uptake and cerebrospinal fluid (CSF) concentration of amyloid-beta 1-42 (Abeta(1-42)) or tau proteins are promising biomarkers in the diagnosis of Alzheimer's disease (AD). There is still uncertainty regarding any association between decreased FDG uptake and alterations in CSF markers. METHODS: The relationship between FDG uptake, CSF Abeta(1-42) and total tau (T-tau), as well as the Mini-Mental State Examination (MMSE) score was investigated in 34 subjects with probable AD using step-wise linear regression. FDG uptake was scaled to the pons. RESULTS: Scaled FDG uptake was significantly reduced in the probable AD subjects compared to 17 controls bilaterally in the precuneus/posterior cingulate area, angular gyrus/inferior parietal cortex, inferior temporal/midtemporal cortex, midfrontal cortex, and left caudate. Voxel-based single-subject analysis of the probable AD subjects at p < 0.001 (uncorrected) revealed a total volume of significant hypometabolism ranging from 0 to 452 ml (median 70 ml). The total hypometabolic volume was negatively correlated with the MMSE score, but it was not correlated with the CSF measures. VOI-based step-wise linear regression revealed that scaled FDG uptake in the precuneus/posterior cingulate was negatively correlated with CSF Abeta(1-42). Scaled FDG uptake in the caudate was positively correlated with CSF T-tau. CONCLUSION: The extent and local severity of the reduction in FDG uptake in probable AD subjects are associated with cognitive impairment. In addition, there appears to be a relationship between local FDG uptake and CSF biomarkers which differs between different brain regions.

Mesolimbic white matter connectivity mediates the preference for sweet food.

Dopaminergic brain structures like the nucleus accumbens (NAc) are thought to encode the incentive salience of palatable foods motivating appetitive behaviour. Animal studies have identified neural networks mediating the regulation of hedonic feeding that comprise connections of the NAc with the ventral tegmental area (VTA) and the lateral hypothalamus (LH). Here, we investigated how structural connectivity of these pathways relates to individual variability in decisions on sweet food consumption in humans. We therefore combined probabilistic tractography on diffusion imaging data from 45 overnight fasted lean to overweight participants with real decisions about high and low sugar food consumption. Across all individuals, sugar preference and connectivity strength were not directly related, however, multiple regression analysis revealed interaction of mesolimbic structure and sugar preference to depend on individuals' BMI score. In overweight individuals (BMI: ≥25 kg/m², N = 22) higher sugar preference was thereby specifically related to stronger connectivity within the VTA-NAc pathway while the opposite pattern emerged in participants with normal BMI (BMI: <25 kg/m², N = 23). Our structural results complement previous functional findings on the critical role of the human mesolimbic system for regulating hedonic eating in overweight individuals.

Cognitive Control Modulates Effects of Episodic Simulation on Delay Discounting in Aging.

Enhancing prospective thinking by tagging the future with specific episodic events has been shown to reduce delay discounting in young age ("tag-effect"). So far, it is unclear whether such beneficial effect extends to old adulthood. Since the general ability of future thinking and cognitive control are crucial modulators of temporal discounting in young age, potential age-related decline in these functions might impact on the effect. We focused on this issue by combining functional magnetic resonance imaging (fMRI) with an established intertemporal choice task including episodic "tags" in healthy older participants. Future thinking ability was assessed using autobiographical interviews for future event simulations and a visual search task was applied to assess participants' cognitive control ability. In contrast to previous data in young adults, the group of older participants did not benefit from tagging the future with episodic events. Older participants' cognitive control function was directly associated with discounting rates in the episodic conditions: the less the older adults were able to focus their attention the less they benefited from the inclusion of episodic events. Consistent with this, imaging results revealed that: (a) subjective value (SV) signals in the hippocampus and the anterior cingulate cortex (ACC) as well as; (b) hippocampal-striatal coupling during the episodic condition were positively related to participants' control capacity. Our findings highlight the critical role of executive functioning for the simultaneous integration of episodic information with future value computation in aging. Boosting delay gratification by including episodic tags might hence be limited in older individuals with pronounced decline in distraction control.

Central insulin modulates food valuation via mesolimbic pathways.

Central insulin is thought to act at the neural interface between metabolic and hedonic drives to eat. Here, using pharmacological fMRI, we show that intranasal insulin (INI) changes the value of food cues through modulation of mesolimbic pathways. Overnight fasted participants rated the palatability of food pictures and attractiveness of non-food items (control) after receiving INI or placebo. We report that INI reduces ratings of food palatability and value signals in mesolimbic regions in individuals with normal insulin sensitivity. Connectivity analyses reveal insulinergic inhibition of forward projections from the ventral tegmentum to the nucleus accumbens. Importantly, the strength of this modulation predicts decrease of palatability ratings, directly linking neural findings to behaviour. In insulin-resistant participants however, we observe reduced food values and aberrant central insulin action. These data demonstrate how central insulin modulates the cross-talk between homeostatic and non-homeostatic feeding systems, suggesting that dysfunctions of these neural interactions may promote metabolic disorders.

Combining voxel-based morphometry and diffusion tensor imaging to detect age-related brain changes.

The present study combined optimized voxel-based morphometry and diffusion tensor imaging to detect age-related brain changes. We compared grey matter density maps (grey matter voxel-based morphometry) and white matter fractional anisotropy maps (diffusion tensor imaging-voxel-based morphometry) between two groups of 17 younger and 17 older women. Older women exhibited reduced white matter fractional anisotropy as well as decreased grey matter density most prominently in the frontal, limbic, parietal and temporal lobes. A discriminant analysis identified four frontal and limbic grey and white matter areas that separated the two groups most effectively. We conclude that grey matter voxel-based morphometry and diffusion tensor imaging voxel-based morphometry are well suited for the detection of age-related changes and their combination provides high accuracy when detecting the neural correlates of aging.

Hippocampal-prefrontal encoding activation predicts whether words can be successfully recalled or only recognized.

The main goal of the present fMRI-study was to identify the neural correlates underlying the successful encoding of words which can subsequently be freely recalled or recognized but not recalled. We were particularly interested in common as well as distinct neural substrates of both retrieval modes. To assess qualitatively differently activated brain areas, categorical subsequent memory analyses were applied. In addition, we used linear parametric modulation to detect brain regions associated with "memory-strength". Our findings suggest that the successful verbal encoding of words, which were recognized but not recalled relies on a subset of the regions engaged during successful encoding of freely recalled words. Furthermore, it seems to be dependent on the magnitude of relational binding in a prefrontal-hippocampal circuit whether a word can subsequently be recalled freely or only recognized.