Sex difference in the relationship between salivary testosterone and inter-temporal choice

Humans often prefer a small immediate reward to large reward in the future. This myopic tendency in inter-temporal choice is termed delay discounting, and has been the focus of intensive research in the past decades. Recent studies indicate that the neural regions underlying delay discounting are influenced by the gonadal steroids. However, the specific relationship between the testosterone levels and delay discounting is unclear at this point, especially in females.The present study investigated the relationship between salivary testosterone concentrations and discounting rates in delay- and probability-discounting tasks with healthy males and females. The results revealed a positive correlation between testosterone concentrations and delay-discounting rates in females and a negative correlation in males. Testosterone concentrations were unrelated to probability-discounting rates. Although causal effects of testosterone cannot be certain in this correlational study, if testosterone directly influenced this behavior, observed sex differences in delay discounting may be evidence of a curvilinear effect of testosterone. Alternatively, the findings may reflect inverse pattern of responsiveness to testosterone between male and female neural systems, or basic sex-difference in the neural mechanism underlying delay-discounting independent of testosterone itself.     

Reduced sensitivity to immediate reward during decision-making in older than younger adults

We examined whether older adults differ from younger adults in the degree to which they favor immediate over delayed rewards during decision-making. To examine the neural correlates of age-related differences in delay discounting we acquired functional MR images while participants made decisions between smaller but sooner and larger but later monetary rewards. The behavioral results show age-related reductions in delay discounting. Less impulsive decision-making in older adults was associated with lower ventral striatal activations to immediate reward. Furthermore, older adults showed an overall higher percentage of delayed choices and reduced activity in the dorsal striatum than younger adults. This points to a reduced reward sensitivity of the dorsal striatum in older adults. Taken together, our findings indicate that less impulsive decision-making in older adults is due to a reduced sensitivity of striatal areas to reward. These age-related changes in reward sensitivity may result from transformations in dopaminergic neuromodulation with age.     

Single units in the pigeon brain integrate reward amount and time-to-reward in an impulsive choice task

BACKGROUND: Animals prefer small over large rewards when the delays preceding large rewards exceed an individual tolerance limit. Such impulsive choice behavior occurs even in situations in which alternative strategies would yield more optimal outcomes. Behavioral research has shown that an animal's choice is guided by the alternative rewards' subjective values, which are a function of reward amount and time-to-reward. Despite increasing knowledge about the pharmacology and anatomy underlying impulsivity, it is still unknown how the brain combines reward amount and time-to-reward information to represent subjective reward value. RESULTS: We trained pigeons to choose between small, immediate rewards and large rewards delivered after gradually increasing delays. Single-cell recordings in the avian Nidopallium caudolaterale, the presumed functional analog of the mammalian prefrontal cortex, revealed that neural delay activation decreased with increasing delay length but also covaried with the expected reward amount. This integrated neural response was modulated by reward amount and delay, as predicted by a hyperbolical equation, of subjective reward value derived from behavioral studies. Furthermore, the neural activation pattern reflected the current reward preference and the time point of the shift from large to small rewards. CONCLUSIONS: The reported activity was modulated by the temporal devaluation of the anticipated reward in addition to reward amount. Our findings contribute to the understanding of neuropathologies such as drug addiction, pathological gambling, frontal lobe syndrome, and attention-deficit disorders, which are characterized by inappropriate temporal discounting and increased impulsiveness.     

Functional parameters of delay discounting assessment tasks: order of presentation

Several variants in the methods used to estimate delay discounting (DD) have been associated with within-subject differences in degree of DD. This study compared variants in the order of presentation of reward and delay values during assessment of DD of hypothetical cash. Participants were randomly assigned to one of two groups. For one group, the immediate reward values were presented in Ascending order and for the other, they were presented in Descending order. In addition, all participants completed a DD task with the reward values presented in a Random order. Degree of DD, calculated as area under the curve (AUC), was similar between the Ascending and Descending procedures, and was significantly higher with the Random procedure. Within-subjects AUC were positively correlated. Reaction times within choice trials changed systematically as a function of order of presentation of the immediate rewards, and distance to the indifference point within each delay value. Reaction times appear to parallel the effort involved in making the individual choices. Some procedural variants in the assessment of DD yield differences in behavior during the assessment task that affect the magnitude of the estimated delay discounting. Thus, the absolute magnitude of DD may not be directly comparable between methods.     

Within-subject comparison of degree of delay discounting using titrating and fixed sequence procedures

Different procedures are often used across experiments to estimate the degree of delay discounting, a common measure of impulsivity. In all procedures, participants indicate their choice between a reward available immediately and one available after a delay. The present experiment determined whether there are differences in the degree of discounting for a hypothetical $100 produced by a procedure that titrates the immediate amount (titrating sequence procedure) versus a procedure that presents a fixed sequence of immediate amounts (fixed sequence procedure) using a within-subject design. The adult human participants showed no significant differences in degree of discounting between procedures as assessed by a hyperboloid model and the Area Under the Curve. Furthermore, the Area Under the Curve values from the two procedures showed a strong positive correlation. These findings suggest there may be no systematic difference between the degree of delay discounting as estimated by the titrating sequence and fixed sequence procedures. Given the apparent similarities in the results, it appears researchers may be justified in basing their choice of which procedure to use on convenience.     

Insulin,Central Dopamine D2 Receptors,and Monetary Reward Discounting in Obesity

Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [¹¹C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including β-cell function, interact to affect reward discounting in humans.     

Led into Temptation? Rewarding Brand Logos Bias the Neural Encoding of Incidental Economic Decisions

Human decision-making is driven by subjective values assigned to alternative choice options. These valuations are based on reward cues. It is unknown, however, whether complex reward cues, such as brand logos, may bias the neural encoding of subjective value in unrelated decisions. In this functional magnetic resonance imaging (fMRI) study, we subliminally presented brand logos preceding intertemporal choices. We demonstrated that priming biased participants' preferences towards more immediate rewards in the subsequent temporal discounting task. This was associated with modulations of the neural encoding of subjective values of choice options in a network of brain regions, including but not restricted to medial prefrontal cortex. Our findings demonstrate the general susceptibility of the human decision making system to apparently incidental contextual information. We conclude that the brain incorporates seemingly unrelated value information that modifies decision making outside the decision-maker's awareness.     

The neural basis of cultural differences in delay discounting

People generally prefer to receive rewarding outcomes sooner rather than later. Such preferences result from delay discounting, or the process by which outcomes are devalued for the expected delay until their receipt. We investigated cultural differences in delay discounting by contrasting behaviour and brain activity in separate cohorts of Western (American) and Eastern (Korean) subjects. Consistent with previous reports, we find a dramatic difference in discounting behaviour, with Americans displaying much greater present bias and elevated discount rates. Recent neuroimaging findings suggest that differences in discounting may arise from differential involvement of either brain reward areas or regions in the prefrontal and parietal cortices associated with cognitive control. We find that the ventral striatum is more greatly recruited in Americans relative to Koreans when discounting future rewards, but there is no difference in prefrontal or parietal activity. This suggests that a cultural difference in emotional responsivity underlies the observed behavioural effect. We discuss the implications of this research for strategic interrelations between Easterners and Westerners.     

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD.     

Microstructure abnormalities in adolescents with internet addiction disorder

Background

Recent studies suggest that internet addiction disorder (IAD) is associated with structural abnormalities in brain gray matter. However, few studies have investigated the effects of internet addiction on the microstructural integrity of major neuronal fiber pathways, and almost no studies have assessed the microstructural changes with the duration of internet addiction.

Methodology/Principal Findings

We investigated the morphology of the brain in adolescents with IAD (N = 18) using an optimized voxel-based morphometry (VBM) technique, and studied the white matter fractional anisotropy (FA) changes using the diffusion tensor imaging (DTI) method, linking these brain structural measures to the duration of IAD. We provided evidences demonstrating the multiple structural changes of the brain in IAD subjects. VBM results indicated the decreased gray matter volume in the bilateral dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the orbitofrontal cortex (OFC), the cerebellum and the left rostral ACC (rACC). DTI analysis revealed the enhanced FA value of the left posterior limb of the internal capsule (PLIC) and reduced FA value in the white matter within the right parahippocampal gyrus (PHG). Gray matter volumes of the DLPFC, rACC, SMA, and white matter FA changes of the PLIC were significantly correlated with the duration of internet addiction in the adolescents with IAD.

Conclusions

Our results suggested that long-term internet addiction would result in brain structural alterations, which probably contributed to chronic dysfunction in subjects with IAD. The current study may shed further light on the potential brain effects of IAD.     

Pathological gambling severity is associated with impulsivity in a delay discounting procedure

Research and clinical expertise indicates that impulsivity is an underlying feature of pathological gambling. This study examined the extent to which impulsive behavior, defined by the rate of discounting delayed monetary rewards, varies with pathological gambling severity, assessed by the South Oaks Gambling Screen (SOGS). Sixty-two pathological gamblers completed a delay discounting task, the SOGS, the Eysenck impulsivity scale, the Addiction Severity Index (ASI), and questions about gambling and substance use at intake to outpatient treatment for pathological gambling. In the delay discounting task, participants chose between a large delayed reward (US $1000) and smaller more immediate rewards (US $1-$999) across a range of delays (6h to 25 years). The rate at which the delayed reward was discounted (k value) was derived for each participant and linear regression was used to identify the variables that predicted k values. Age, gender, years of education, substance abuse treatment history, and cigarette smoking history failed to significantly predict k values. Scores on the Eysenck impulsivity scale and the SOGS both accounted for a significant proportion of the variance in k values. The predictive value of the SOGS was 1.4 times that of the Eysenck scale. These results indicate that of the measures tested, gambling severity was the best single predictor of impulsive behavior in a delay discounting task in this sample of pathological gamblers.     

MRI Detects Brain Reorganization after Human Umbilical Tissue-Derived Cells (hUTC) Treatment of Stroke in Rat

Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential technology for neurorestoration and improvement of functional outcomes following stroke. Male Wistar rats were subjected to a transient middle cerebral artery occlusion (tMCAo) and were intravenously administered hUTC (N = 11) or vehicle (N = 10) 48 hrs after stroke. White matter and vascular reorganization was monitored over a 12-week period using MRI and histopathology. MRI results were correlated with neurological functional and histology outcomes to demonstrate that MRI can be a useful tool to measure structural recovery after stroke. MRI revealed a significant reduction in the ventricular volume expansion and improvement in cerebral blood flow (CBF) in the hUTC treated group compared to vehicle treated group. Treatment with hUTC resulted in histological and functional improvements as evidenced by enhanced expression of vWF and synaptophysin, and improved outcomes on behavioral tests. Significant correlations were detected between MRI ventricular volumes and histological lesion volume as well as number of apoptotic cells. A positive correlation was also observed between MRI CBF or cerebral blood volume (CBV) and histological synaptic density. Neurological functional tests were also significantly correlated with MRI ventricular volume and CBV. Our data demonstrated that MRI measurements can detect the effect of hUTC therapy on the brain reorganization and exhibited positive correlation with histological measurements of brain structural changes and functional behavioral tests after stroke. MRI ventricular volumes provided the most sensitive index in monitoring brain remodeling and treatment effects and highly correlated with histological and functional measurements.     

Are Frontal Cognitive and Atrophy Patterns Different in PSP and bvFTD? A Comparative Neuropsychological and VBM Study

Progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration (FTD) are two clinicohistological entities that share a severe prefrontal syndrome. To what extent do the cognitive syndrome and the location of the underlying brain atrophy unify or segregate these entities? Here, we examined the clinical and radiological patterns of frontal involvement and the neural bases of the cognitive dysfunctions observed in the Richardson form of PSP and the behavioral variant of FTD (bvFTD). The cognitive profile and grey and white matter volume of PSP (n = 19) and bvFTD (n = 16) patients and control participants (n = 18) were compared using a standard battery of neuropsychological tests and voxel-based morphometry (VBM), respectively. Analyses of correlations between neuropsychological and morphometric data were additionally performed. The severity and qualitative pattern of cognitive dysfunction was globally similar between the two patient groups. Grey matter volume was decreased in widespread frontal areas and in the temporal uncus in bvFTD, while it was decreased in the frontal and temporal lobes as well as in the thalamus in PSP. We also found an unexpected involvement of the frontal rectal gyrus in PSP patients compared to controls. Correlation analyses yielded different results in the two groups, with no area showing significant correlations in PSP patients, while several frontal and some temporal areas did so in bvFTD patients. In spite of minor neuropsychological and morphological differences, this study shows that the patterns of cognitive dysfunction and atrophy are very similar in PSP and bvFTD. However, executive dysfunction in these diseases may stem from partially divergent cortical and subcortical neural circuits.     

Global and Regional Associations of Smaller Cerebral Gray and White Matter Volumes with Gait in Older People

Background

Gait impairments increase with advancing age and can lead to falls and loss of independence. Brain atrophy also occurs in older age and may contribute to gait decline. We aimed to investigate global and regional relationships of cerebral gray and white matter volumes with gait speed, and its determinants step length and cadence, in older people.

Methods

In a population-based study, participants aged >60 years without Parkinson''s disease or brain infarcts underwent magnetic resonance imaging and gait measurements using a computerized walkway. Linear regression was used to study associations of total gray and white matter volumes with gait, adjusting for each other, age, sex, height and white matter hyperintensity volume. Other covariates considered in analyses included weight and vascular disease history. Voxel-based morphometry was used to study regional relationships of gray and white matter with gait.

Results

There were 305 participants, mean age 71.4 (6.9) years, 54% male, mean gait speed 1.16 (0.22) m/s. Smaller total gray matter volume was independently associated with poorer gait speed (p = 0.001) and step length (p<0.001), but not cadence. Smaller volumes of cortical and subcortical gray matter in bilateral regions important for motor control, vision, perception and memory were independently associated with slower gait speed and shorter steps. No global or regional associations were observed between white matter volume and gait independent of gray matter volume, white matter hyperintensity volume and other covariates.

Conclusion

Smaller gray matter volume in bilaterally distributed brain networks serving motor control was associated with slower gait speed and step length, but not cadence.     

Adolescent Engagement in Dangerous Behaviors Is Associated with Increased White Matter Maturity of Frontal Cortex

Background

Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence.

Methodology/Principal Findings

We tested this hypothesis in a group of healthy adolescents, age 12–18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14–18, N = 60).

Conclusions/Significance

The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.     

Temporal Discounting Is Associated with an Increased Risk of Mortality among Community-Based Older Persons without Dementia

Background

Temporal discounting is an important determinant of many health and financial outcomes, but we are not aware of studies that have examined the association of temporal discounting with mortality.

Methods

Participants were 406 older persons without dementia from the Rush Memory and Aging Project, a longitudinal cohort study of aging. Temporal discounting was measured using standard preference elicitation questions. Individual discount rates were estimated using a well-established hyperbolic function and used to predict the risk of mortality during up to 5 years of follow-up.

Results

The mean estimate of discounting was 0.45 (SD = 0.33, range: 0.08–0.90), with higher scores indicating a greater propensity to prefer smaller immediate rewards over larger but delayed ones. During up to 5 years of follow-up (mean = 3.6 years), 62 (15% of 406) persons died. In a proportional hazards model adjusted for age, sex, and education, temporal discounting was associated with an increased risk of mortality (HR = 1.103, 95% CI 1.024, 1.190, p = 0.010). Thus, a person with the highest discount rate (score = 0.90) was about twice more likely to die over the study period compared to a person with the lowest discount rate (score = 0.08). Further, the association of discounting with mortality persisted after adjustment for the level of global cognitive function, the burden of vascular risk factors and diseases, and an indicator of psychological well being (i.e., purpose in life).

Conclusion

Temporal discounting is associated with an increased risk of mortality in old age after accounting for global cognitive function and indicators of physical and mental health.     

Differences in Prefrontal,Limbic, and White Matter Lesion Volumes According to Cognitive Status in Elderly Patients with First-Onset Subsyndromal Depression

The purpose of this preliminary study was to test the hypothesis that subsyndromal depression is associated with the volume of medial prefrontal regional gray matter and that of white matter lesions (WMLs) in the brains of cognitively normal older people. We also explored the relationships between subsyndromal depression and medial prefrontal regional gray matter volume, limbic regional gray matter volume, and lobar WMLs in the brains of patients with mild cognitive impairment (MCI) and Alzheimer''s disease (AD). We performed a cross-sectional study comparing patients with subsyndromal depression and nondepressed controls with normal cognition (n = 59), MCI (n = 27), and AD (n = 27), adjusting for sex, age, years of education, and results of the Mini-Mental State Examination. Frontal WML volume was greater, and right medial orbitofrontal cortical volume was smaller in cognitively normal participants with subsyndromal depression than in those without subsyndromal depression. No volume differences were observed in medial prefrontal, limbic, or WML volumes according to the presence of subsyndromal depression in cognitively impaired patients. The absence of these changes in patients with MCI and AD suggests that brain changes associated with AD pathology may override the changes associated with subsyndromal depression.     

Medial Frontal White and Gray Matter Contributions to General Intelligence

The medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) are part of a wider neural network that plays an important role in general intelligence and executive function. We used structural brain imaging to quantify magnetic resonance gray matter volume and diffusion tensor white matter integrity of the mOFC-rACC network in 26 healthy participants who also completed neuropsychological tests of intellectual abilities and executive function. Stochastic tractography, the most effective Diffusion Tensor Imaging method for examining white matter connections between adjacent gray matter regions, was employed to assess the integrity of mOFC-rACC pathways. Fractional anisotropy (FA), which reflects the integrity of white matter connections, was calculated. Results indicated that higher intelligence correlated with greater gray matter volumes for both mOFC and rACC, as well as with increased FA for left posterior mOFC-rACC connectivity. Hierarchical regression analyses revealed that DTI-derived FA of left posterior mOFC-rACC uniquely accounted for 29%–34% of the variance in IQ, in comparison to 11%–16% uniquely explained by gray matter volume of the left rACC. Together, left rACC gray matter volume and white matter connectivity between left posterior mOFC and rACC accounted for up to 50% of the variance in general intelligence. This study is to our knowledge the first to examine white matter connectivity between OFC and ACC, two gray matter regions of interests that are very close in physical proximity, and underscores the important independent contributions of variations in rACC gray matter volume and mOFC-rACC white matter connectivity to individual differences in general intelligence.     

Within-subject differences in degree of delay discounting as a function of order of presentation of hypothetical cash rewards

Procedural variants in estimating delay discounting (DD) have been shown to yield significant differences in estimated degree of DD as well as variations in individual patterns of choice. For example, a recent study found significantly different degrees of DD between groups assessed using either an ascending or descending order of presentation of the immediately available rewards. The purpose of this study was to test for within-subject effects of order of presentation of the immediate rewards in a DD task. In a single session, college students (N = 29) were asked to complete two DD tasks, one with the immediate rewards presented in ascending order and one in descending order. Consistent with previous results, significantly larger mean area under the discounting curve (AUC) was observed when the descending sequence was used compared to the ascending order of presentation; and the correlation between both measurements was moderate. These results suggest that some DD assessment tasks may be sensitive to contextual variables such as order and range of the reward and delay values.