Pregnancy as a window of opportunity for dementia prevention: a narrative review.

Dementia is a debilitating condition with a disproportionate impact on women. While sex differences in longevity contribute to the disparity, the role of the female sex as a biological variable in disease progression is not yet fully elucidated. Metabolic dysfunctions are drivers of dementia etiology, and cardiometabolic diseases are among the most influential modifiable risk factors. Pregnancy is a time of enhanced vulnerability for metabolic disorders. Many dementia risk factors, such as hypertension or blood glucose dysregulation, often emerge for the first time in pregnancy. While such cardiometabolic complications in pregnancy pose a risk to the health trajectory of a woman, increasing her odds of developing type 2 diabetes or chronic hypertension, it is not fully understood how this relates to her risk for dementia. Furthermore, structural and functional changes in the maternal brain have been reported during pregnancy suggesting it is a time of neuroplasticity for the mother. Therefore, pregnancy may be a window of opportunity to optimize metabolic health and support the maternal brain. Healthy dietary patterns are known to reduce the risk of cardiometabolic diseases and have been linked to dementia prevention, yet interventions targeting cognitive function in late life have largely been unsuccessful. Earlier interventions are needed to address the underlying metabolic dysfunctions and potentially reduce the risk of dementia, and pregnancy offers an ideal opportunity to intervene. This review discusses current evidence regarding maternal brain health and the potential window of opportunity in pregnancy to use diet to address neurological health disparities for women.

Taste of common prebiotic oligosaccharides: impact of molecular structure.

Prebiotic oligosaccharides are naturally occurring nondigestible carbohydrates with demonstrated health benefits. They are also a chemically diverse class of nutrients, offering an opportunity to investigate the impact of molecular structure on oligosaccharide taste perception. Accordingly, a relevant question is whether these compounds are detected by the human gustatory system, and if so, whether they elicit sweet or "starchy" taste. Here, in 3 psychophysical experiments, we investigated the taste perception of 3 commercially popular prebiotics [fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylooligosaccharides (XOS)] in highly pure form. Each of these classes of prebiotics differs in the type of glycosyl residue, and position and type of bond between those residues. In experiments I and II, participants were asked to discriminate a total of 9 stimuli [FOS, GOS, XOS; degree of polymerization (DP) of 2, 3, 4] prepared at 75 mM in the presence and absence of lactisole, a sweet receptor antagonist. We found that all 9 compounds were detectable (P < 0.05). We also found that GOS and XOS DP 4 were discriminable even with lactisole, suggesting that their detection was not via the canonical sweet receptor. Accordingly, in experiment III, the taste of GOS and XOS DP 4 were directly compared with that of MOS (maltooligosaccharides) DP 4-6, which has been reported to elicit "starchy" taste. We found that GOS and MOS were perceived similarly although narrowly discriminable, while XOS was easily discriminable from both GOS and MOS. The current findings suggest that the molecular structure of oligosaccharides impacts their taste perception in humans.

TRPM4 and PLCß3 contribute to normal behavioral responses to an array of sweeteners and carbohydrates but PLCß3 is not needed for taste-driven licking for glucose.

The peripheral taste system is more complex than previously thought. The novel taste-signaling proteins TRPM4 and PLCß3 appear to function in normal taste responding as part of Type II taste cell signaling or as part of a broadly responsive (BR) taste cell that can respond to some or all classes of tastants. This work begins to disentangle the roles of intracellular components found in Type II taste cells (TRPM5, TRPM4, and IP3R3) or the BR taste cells (PLCß3 and TRPM4) in driving behavioral responses to various saccharides and other sweeteners in brief-access taste tests. We found that TRPM4, TRPM5, TRPM4/5, and IP3R3 knockout (KO) mice show blunted or abolished responding to all stimuli compared with wild-type. IP3R3 KO mice did, however, lick more for glucose than fructose following extensive experience with the 2 sugars. PLCß3 KO mice were largely unresponsive to all stimuli except they showed normal concentration-dependent responding to glucose. The results show that key intracellular signaling proteins associated with Type II and BR taste cells are mutually required for taste-driven responses to a wide range of sweet and carbohydrate stimuli, except glucose. This confirms and extends a previous finding demonstrating that Type II and BR cells are both necessary for taste-driven licking to sucrose. Glucose appears to engage unique intracellular taste-signaling mechanisms, which remain to be fully elucidated.

Faculty and Student Perceptions of Unauthorized Collaborations in the Preclinical Curriculum: Student or System Failure?

PURPOSE: Unauthorized collaboration among medical students, including the unauthorized provision of assistance and sharing of curricular and assessment materials, is a reported problem. While many faculty view such sharing as academic dishonesty, students do not always perceive these behaviors as problematic. With the trend toward more small-group and team-based learning and the proliferation of resource-sharing and online study aids, collaboration and sharing may have become a student norm. This multi-institutional, qualitative study examined faculty and student perceptions of and student motivations for unauthorized collaboration. METHOD: Using a constructivist approach, the authors conducted scenario-prompted semistructured interviews with faculty and students in the preclinical curriculum. Participants were asked to reflect on scenarios of unauthorized collaboration and discuss their perceptions of student motivation and the influence of personal or environmental factors. The authors performed inductive thematic analysis of the interview transcripts using open and axial coding followed by abstraction and synthesis of themes. RESULTS: Twenty-one faculty and 16 students across 3 institutions were interviewed in 2021. There was variation in perceptions among faculty and among students, but little variation between faculty and students. Both participant groups identified the same 3 areas of tension/themes: faculty/curriculum goals vs student goals, inherent character traits vs modifiable behavioral states, and student relationships with their peer group vs their relationships with the medical education system. Student behaviors were perceived to be influenced by their environment and motivated by the desire to help peers. Participants suggested cultivating trust between students and the education system, environmental interventions, and educating students about acceptable and unacceptable behaviors to prevent unauthorized collaboration. CONCLUSIONS: Given the various tensions and positive motivations behind unauthorized collaborations, institutions should consider explicitly preparing students to make thoughtful decisions when faced with competing priorities in addition to developing mitigation strategies that address the environment and its interactions with students.

Potential biomarker of brain response to opioid antagonism in adolescents with eating disorders: a pilot study.

Background: Eating Disorders (ED) affect up to 5% of youth and are associated with reward system alterations and compulsive behaviors. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and/or purging. The presumed mechanism of action is blockade of reward activation; however, not all patients respond, and the optimal dose is unknown. Developing a tool to detect objective drug response in the brain will facilitate drug development and therapeutic optimization. This pilot study evaluated neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED. Methods: Youth aged 13-21 with binge/purge ED completed functional magnetic resonance imaging (fMRI) pre- and post-oral naltrexone. fMRI detected blood oxygenation-level dependent (BOLD) signal at rest and during two reward probes (monetary incentive delay, MID, and passive food view, PFV) in predefined regions of interest associated with reward and inhibitory control. Effect sizes for Δ%BOLD (post-naltrexone vs. baseline) were estimated using linear mixed effects modeling. Results: In 12 youth (16-21 years, 92% female), BOLD signal changes were detected following naltrexone in the nucleus accumbens during PFV (Δ%BOLD -0.08 ± 0.03; Cohen's d -1.06, p = 0.048) and anterior cingulate cortex during MID (Δ%BOLD 0.06 ± 0.03; Cohen's d 1.25, p = 0.086). Conclusion: fMRI detected acute reward pathway modulation in this small sample of adolescents with binge/purge ED. If validated in future, larger trials, task-based Δ%BOLD detected by fMRI may serve as a pharmacodynamic biomarker of opioid antagonism to facilitate the development of novel therapeutics targeting the reward pathway, enable quantitative pharmacology trials, and inform drug dosing. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04935931, NCT#04935931.

Quality control in resting-state fMRI: the benefits of visual inspection.

Background: A variety of quality control (QC) approaches are employed in resting-state functional magnetic resonance imaging (rs-fMRI) to determine data quality and ultimately inclusion or exclusion of a fMRI data set in group analysis. Reliability of rs-fMRI data can be improved by censoring or "scrubbing" volumes affected by motion. While censoring preserves the integrity of participant-level data, including excessively censored data sets in group analyses may add noise. Quantitative motion-related metrics are frequently reported in the literature; however, qualitative visual inspection can sometimes catch errors or other issues that may be missed by quantitative metrics alone. In this paper, we describe our methods for performing QC of rs-fMRI data using software-generated quantitative and qualitative output and trained visual inspection. Results: The data provided for this QC paper had relatively low motion-censoring, thus quantitative QC resulted in no exclusions. Qualitative checks of the data resulted in limited exclusions due to potential incidental findings and failed pre-processing scripts. Conclusion: Visual inspection in addition to the review of quantitative QC metrics is an important component to ensure high quality and accuracy in rs-fMRI data analysis.

Taste Detection of Maltooligosaccharides with Varying Degrees of Polymerization.

Previous studies have shown that humans can taste maltooligosaccharides [MOS; degree of polymerization (DP) of 3-20] but not maltopolysaccharides (MPS; DP of >20) and that their taste detection is independent of the canonical sweet taste receptor. The objectives of this study were to determine the DP ranges of target stimuli that are tasted and further to investigate the impact of DP on taste detectability. To achieve this goal, we prepared three food-grade MOS samples with narrow DP ranges using flash chromatography: low (4-6), medium (7-12), and high (14-21) DP samples. Following sample preparation, we asked subjects to discriminate the MOS stimuli from blanks after the stimuli were swabbed on the tip of tongue. All stimuli were initially presented at 75 mM. Acarbose, an α-glucosidase inhibitor, was added to all stimuli, including blanks, to prevent oral hydrolysis of MOS. After determining that all three MOS samples were detected at a significant degree, we conducted follow-up studies to explore whether the detection of these samples differed at a range of concentrations (18-56 mM). The results showed that detection rates of medium- and high-DP MOS varied in a concentration-dependent manner (p < 0.05). In contrast, low-DP MOS showed a consistent detection rate across concentrations tested. These results demonstrate that humans can taste MOS stimuli of all chain lengths and that relative taste detection rates are generally similar across MOS with varying chain lengths.

The role of saliva in taste and food intake.

Saliva is well-described in oral food processing, but its role in taste responsiveness remains understudied. Taste stimuli must dissolve in saliva to reach their receptor targets. This allows the constituents of saliva the opportunity to interact with taste stimuli and their receptors at the most fundamental level. Yet, despite years of correlational data suggesting a role for salivary proteins in food preference, there were few experimental models to test the role of salivary proteins in taste-driven behaviors. Here we review our experimental contributions to the hypothesis that salivary proteins can alter taste function. We have developed a rodent model to test how diet alters salivary protein expression, and how salivary proteins alter diet acceptance and taste. We have found that salivary protein expression is modified by diet, and these diet-induced proteins can, in turn, increase the acceptance of a bitter diet. The change in acceptance is in part mediated by a change in taste signaling. Critically, we have documented increased detection threshold, decreased taste nerve signaling, and decreased oromotor responding to quinine when animals have increases in a subset of salivary proteins compared to control conditions.

Effect of Cognitive Reserve on Physiological Measures of Cognitive Workload in Older Adults with Cognitive Impairments.

BACKGROUND: Cognitive reserve may protect against cognitive decline. OBJECTIVE: This cross-sectional study investigated the association between cognitive reserve and physiological measures of cognitive workload in older adults with cognitive impairment. METHODS: 29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MoCA: 20±7) and 19 with normal cognition (age: 74±6; 11 (58%) women; MoCA: 28±2) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve. Linear mixed models evaluated the main effects of cognitive status, CRIq, and the interaction effect of CRIq by cognitive status on ERP and ICA. RESULTS: The interaction effect of CRIq total score by cognitive status on P3 ERP and ICA was not significant. However, higher CRIq total scores were associated with lower ICA (p = 0.03). The interaction effects of CRIq subscores showed that Work Activity affected P3 amplitude (p = 0.03) and ICA (p = 0.03) differently between older adults with and without cognitive impairments. Similarly, Education affected ICA (p = 0.02) differently between the two groups. No associations were observed between CRIq and P3 latency. CONCLUSION: Specific components of cognitive reserve affect cognitive workload and neural efficiency differently in older adults with and without cognitive impairments.

Pre-post intervention exploring cognitive function and relationships with weight loss, intervention adherence and dropout.

Objective: To evaluate the association between baseline cognitive function, intervention dropout, adherence and 3-month weight loss (WL) when controlling for confounding demographic variables. Methods: 107 (Mage = 40.9 yrs.), BMI in the overweight and obese range (BMI = 35.6 kg/m2), men (N = 17) and women (N = 90) completed a 3-month WL intervention. Participants attended weekly behavioral sessions, comply with a reduced calorie diet, and complete 100 min of physical activity (PA)/wk. Cognitive function tasks at baseline included Flanker (attention), Stroop (executive control) and working memory, demographics, body weight and cardiovascular fitness were assessed at baseline. Session attendance, adherence to PA and diet were recorded weekly. Results: Baseline attention was positively correlated with age (p < .05), education (p < .05), attendance (p < .05), diet (p < .05) and PA (p < .05). Baseline executive control (p < .05) and working memory (p < .05) were each associated with % WL. Baseline executive control (p < .01) and working memory (p < .001) were also each associated with education. ANOVA indicated that baseline attention (p < .01) was associated with WL, specifically for comparing those who achieved 5-10% WL (p < .01) and those who achieved greater than 10% WL (p < .01) to those who dropped. Significance: Results suggest that stronger baseline attention is associated with completion of a 3-mo. WL intervention. Executive control and working memory are associated with amount of WL achieved. NCT registration: US NIH Clinical Trials, NCT01664715.

Racial and socioeconomic disparities in cost and postoperative complications following sacrocolpopexy in a US National Inpatient Database.

PURPOSE: We sought to determine the association between socioeconomic factors, procedural costs, and postoperative complications among patients who underwent sacrocolpopexy. METHODS: The 2016-2017 US National Inpatient Sample from the Healthcare Cost and Utilization Project was used to identify females > 18 years of age with an ICD10 diagnosis code of apical prolapse who received open or laparoscopic/robotic sacrocolpopexy. We analyzed relationships between socioeconomic factors, procedural costs, and postoperative complications in these patients. Multivariate logistic and linear regressions were used to identify variables associated with increased complications and costs, respectively. RESULTS: We identified 4439 women who underwent sacrocolpopexy, of which 10.7% had complications. 34.6% of whites, 29.1% of Blacks, 29% of Hispanics, and 34% of Others underwent a laparoscopic/robotic procedure. Hispanic patients had the highest median charge associated with surgical admission for sacrocolpopexy at $51,768, followed by Other ($44,522), White ($43,471), and Black ($40,634) patients. Procedure being within an urban teaching hospital (+ $2602), laparoscopic/robotic (+ $6790), or in the West (+ $9729) were associated with a significantly higher median cost of surgical management. CONCLUSIONS: In women undergoing sacrocolpopexy, the protective factors against postoperative complications included private insurance status, a laparoscopic approach, and concurrent hysterectomy. Procedures held within an urban teaching hospital, conducted laparoscopically/robotically or in the West are associated with significantly higher costs of surgical management. Hispanic patients observe significantly higher procedure charges and costs, possibly resulting from the large number of this ethnic group living in the Western United States.

Chromatographic fractionation of food-grade oligosaccharides: Recognizing and avoiding sensory-relevant impurities.

Flash chromatography utilizing microcrystalline cellulose (MCC) stationary phases and aqueous ethanol mobile phases have shown promise for the production of food-grade oligosaccharides. The current work extends the scope of these systems by demonstrating their use for the production of food-grade maltooligosaccharide preparations enriched in high degree of polymerization (DP) components. Furthermore, it is shown herein that caution must be exercised when using these MCC-based chromatographic systems in order to avoid sensory-relevant contamination of the final oligosaccharide preparations. Such contamination, most notably off-taste, is shown to arise from impurities common to commercially available MCC that manifest under certain chromatographic scenarios. A mitigation strategy based on washing the stationary phase with appropriate aqueous-ethanol solutions (i.e., accounting for the entire mobile phase concentration range) prior to oligosaccharide fractionation is presented as a means by which to avoid contamination.

Autonomic nervous system markers of music-elicited analgesia in people with fibromyalgia: A double-blind randomized pilot study.

Purpose: To investigate the feasibility of using music listening by adults with fibromyalgia (FM) as a potential tool for reducing pain sensitivity. Patients and methods: We report results from a double-blind two-arm parallel randomized pilot study (NCT04059042) in nine participants with FM. Pain tolerance and threshold were measured objectively using quantitative sensory tests; autonomic nervous system (ANS) reactivity was measured with an electrocardiogram. Participants were randomized to listen to instrumental Western Classical music or a nature sound control to test whether music listening elicits greater analgesic effects over simple auditory distraction. Participants also completed separate control testing with no sound that was counterbalanced between participants. Results: Participants were randomized 1:1 to music or nature sounds (four Music and five Nature). Although the groups were not different on FM scores, the Music group had marginally worse temporal pain summation (p = 0.06), and the Nature group had higher anxiety scores (p < 0.05). Outcome measures showed a significant difference between groups in the magnitude of change in temporal summation between sessions (p < 0.05), revealing that the Nature group had greater pain reduction during audio compared to silence mode, while the Music group had no difference between the sessions. No significant effects were observed for either mechanical pain tolerance or ANS testing. Within the Music group, there was a trend of vagal response increase from baseline to music listening, but it did not reach statistical significance; this pattern was not observed in the Nature group. Conclusion: Auditory listening significantly altered pain responses. There may be a greater vagal response to music vs. nature sounds; however, results could be due to group differences in pain and anxiety. This line of study will help in determining whether music could be prophylactic for people with FM when acute pain is expected.

Testing and Optimizing Guided Thinking Tasks to Promote Physical Activity: Protocol for a Randomized Factorial Trial.

BACKGROUND: Insufficient physical activity is associated with various health risks; however, most current physical activity interventions have critical barriers to scalability. Delivering interventions via technology and identifying active and inert components in early-phase development are ways to build more efficient and scalable interventions. We developed a novel intervention to promote physical activity that targets 3 brief guided thinking tasks, separately and in combination, using brief audio recordings: (1) episodic future thinking (EFT), (2) positive affective imagery (PAI), and (3) planning. OBJECTIVE: The aim of this GeT (Guided Thinking) Active study is to optimize a scalable guided thinking intervention to promote physical activity using principles of the Multiphase Optimization Strategy (MOST). Mechanism-focused analyses will inform which components are optimal candidates for inclusion in an intervention package and which need refinement. METHODS: We will enroll 192 participants randomized to receive intervention components delivered via an audio recording that they will listen to prior to weekly in-lab physical activity sessions. Participants in the high dose conditions will also be instructed to listen to the audio recording 4 additional days each week. We will evaluate effects of the components on physical activity over 6 weeks in a 2 (EFT vs recent thinking) × 2 (PAI vs neutral imagery) × 2 (planning vs no planning) × 2 (dose: 5×/week vs 1×/week) full factorial randomized trial. RESULTS: The National Cancer Institute funded this study (R21CA260360) on May 13, 2021. Participant recruitment began in February 2022. Data analysis will begin after the completion of data collection. CONCLUSIONS: The GeT Active study will result in a scalable, audio-recorded intervention that will accelerate progress toward the full development of guided thinking interventions to promote physical activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT05235360; https://clinicaltrials.gov/ct2/show/NCT05235360. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40908.

Dementia risk and dynamic response to exercise: A non-randomized clinical trial.

BACKGROUND: Physical exercise may support brain health and cognition over the course of typical aging. The goal of this nonrandomized clinical trial was to examine the effect of an acute bout of aerobic exercise on brain blood flow and blood neurotrophic factors associated with exercise response and brain function in older adults with and without possession of the Apolipoprotein epsilon 4 (APOE4) allele, a genetic risk factor for developing Alzheimer's. We hypothesized that older adult APOE4 carriers would have lower cerebral blood flow regulation and would demonstrate blunted neurotrophic response to exercise compared to noncarriers. METHODS: Sixty-two older adults (73±5 years old, 41 female [67%]) consented to this prospectively enrolling clinical trial, utilizing a single arm, single visit, experimental design, with post-hoc assessment of difference in outcomes based on APOE4 carriership. All participants completed a single 15-minute bout of moderate-intensity aerobic exercise. The primary outcome measure was change in cortical gray matter cerebral blood flow in cortical gray matter measured by magnetic resonance imaging (MRI) arterial spin labeling (ASL), defined as the total perfusion (area under the curve, AUC) following exercise. Secondary outcomes were changes in blood neurotrophin concentrations of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and brain derived neurotrophic factor (BDNF). RESULTS: Genotyping failed in one individual (n = 23 APOE4 carriers and n = 38 APOE4 non-carriers) and two participants could not complete primary outcome testing. Cerebral blood flow AUC increased immediately following exercise, regardless of APOE4 carrier status. In an exploratory regional analyses, we found that cerebral blood flow increased in hippocampal brain regions, while showing no change in cerebellum across both groups. Among high inter-individual variability, there were no significant changes in any of the 3 neurotrophic factors for either group immediately following exercise. CONCLUSIONS: Our findings show that both APOE4 carriers and non-carriers show similar effects of exercise-induced increases in cerebral blood flow and neurotrophic response to acute aerobic exercise. Our results provide further evidence that acute exercise-induced increases in cerebral blood flow may be regional specific, and that exercise-induced neurotrophin release may show a differential effect in the aging cardiovascular system. Results from this study provide an initial characterization of the acute brain blood flow and neurotrophin responses to a bout of exercise in older adults with and without this known risk allele for cardiovascular disease and Alzheimer's disease. TRIAL REGISTRATION: Dementia Risk and Dynamic Response to Exercise (DYNAMIC); Identifier: NCT04009629.

Functional Brain Connectivity and Inhibitory Control in Older Adults: A Preliminary Study.

According to the inhibition deficit hypothesis, the ability to inhibit unwanted or irrelevant thoughts and behaviors decreases with age, which can have a significant impact on cognitive and emotional processing. However, studies examining inhibition and age have shown mixed results, with some studies finding a decrease in inhibitory control as individuals age, while others have found no relationship. The goal of this proof-of-concept study was to examine the underlying neural mechanisms that may explain why some older adults are better than others at inhibitory control by investigating the relationship between resting-state functional connectivity (rsFC) of the salience network, a network critical for detecting and focusing attention toward relevant stimuli while ignoring irrelevant information in the environment, and a behavioral measure of inhibitory control (Stroop Task interference score) in a sample of 65 healthy older individuals (ages 65+). Results revealed no direct effect of age on Stroop performance; however, there was an indirect effect of age on Stroop performance through rsFC. These results suggest that rsFC of the salience network may be an important factor to consider when it comes to understanding individual differences in inhibitory control behavior among older adults.

Taste perception of cyclic oligosaccharides: α, ß, and γ cyclodextrins.

Oligosaccharides, a subclass of complex carbohydrates, occur both naturally in foods and as a result of oral starch digestion. We have previously shown that humans can taste maltooligosaccharides (MOS) and that their detection is independent of the canonical sweet taste receptor. While MOSs most commonly occur in a linear form, they can also exist in cyclic structures, referred to as cyclodextrins (CD). The aim of this study was to investigate how the structure of the MOS backbone (i.e. cyclic form) and the size (i.e. degree of polymerization; DP) affect their taste perception. We tested taste detection of cyclodextrins with DP of 6, 7, and 8 (i.e. α-, ß-, and γ-CD, respectively) in the presence and absence of lactisole, a sweet receptor antagonist. We found that subjects could detect the taste of cyclodextrins in aqueous solutions at a significant level (P < 0.05), but were not able to detect them in the presence of lactisole (P > 0.05). These findings suggest that the cyclodextrins, unlike their linear analogs, are ligands of the human sweet taste receptor, hT1R2/hT1R3. Study findings are discussed in terms of how chemical structures may contribute to tastes of saccharides.

Differential Probability Discounting Rates of Gamblers in an American Indian Population.

Probability discounting, a subset of behavioral economic research, has a rich history of investigating choice behavior, especially as it pertains to risky decision making. Gambling involves both choice behavior and risky decision making which makes it an ideal behavior to investigate with discounting tasks. With proximity to a casino being one of the biggest risk factors, studies into the American Indian population have been a neglected population of study. Using outcome measures from a pre-scan probability discounting task, the current study equated the scan task to evaluate behavioral and neurobiological differences in gamblers vs. non-gamblers. Gamblers showed differences in behavioral tasks (lower discounting rates) but not in patterns of neural activation.

EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid.

BACKGROUND: Although growing evidence links beta-amyloid (Aß) and neuronal hyperexcitability in preclinical mouse models of Alzheimer's disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aß (Aß+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event-related power between CNAß+ and CNAß-. METHODS: Seventeen CNAß+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 ± 2) and 17 CNAß- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget-target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 amplitude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aß standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. RESULTS: The P3 peak amplitude of the task difference effect at Fz was lower in the CNAß+ group (P = 0.048). Similarly, power was lower in the delta band for nontargets at Fz in the CNAß+ participants (P = 0.04). The CNAß+ participants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aß SUVR and the latency of the 1-back (r = - 0.69; P = 0.003) and 2-back (r = - 0.69; P = 0.004) of the task difference effect at channel Fz in the CNAß+ group. CONCLUSIONS: Our data suggest that the elevated amyloid in cognitively normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.

Delay Discounting in Established and Proposed Behavioral Addictions: A Systematic Review and Meta-Analysis.

Steep delay discounting, or a greater preference for smaller-immediate rewards over larger-delayed rewards, is a common phenomenon across a range of substance use and psychiatric disorders. Non-substance behavioral addictions (e.g., gambling disorder, internet gaming disorder, food addiction) are of increasing interest in delay discounting research. Individual studies have reported steeper discounting in people exhibiting various behavioral addictions compared to controls or significant correlations between discounting and behavioral addiction scales; however, not all studies have found significant effects. To synthesize the published research in this area and identify priorities for future research, we conducted a pre-registered systematic review and meta-analysis (following PRISMA guidelines) of delay discounting studies across a range of behavioral addiction categories. The final sample included 78 studies, yielding 87 effect sizes for the meta-analysis. For studies with categorical designs, we found statistically significant, medium-to-large effect sizes for gambling disorder (Cohen's d = 0.82) and IGD (d = 0.89), although the IGD effect size was disproportionately influenced by a single study (adjusted d = 0.53 after removal). Categorical internet/smartphone studies were non-significant (d = 0.16, p = 0.06). Aggregate correlations in dimensional studies were statistically significant, but generally small magnitude for gambling (r = 0.22), internet/smartphone (r = 0.13) and food addiction (r = 0.12). Heterogeneity statistics suggested substantial variability across studies, and publication bias indices indicated moderate impact of unpublished or small sample studies. These findings generally suggest that some behavioral addictions are associated with steeper discounting, with the most robust evidence for gambling disorder. Importantly, this review also highlighted several categories with notably smaller effect sizes or categories with too few studies to be included (e.g., compulsive buying, exercise addiction). Further research on delay discounting in behavioral addictions is warranted, particularly for categories with relatively few studies.