Greater reliance on model-free learning in adolescent anorexia nervosa: An examination of dual-system reinforcement learning.

Alterations in learning and decision-making systems are thought to contribute to core features of anorexia nervosa (AN), a psychiatric disorder characterized by persistent dietary restriction and weight loss. Instrumental learning theory identifies a dual-system of habit and goal-directed decision-making, linked to model-free and model-based reinforcement learning algorithms. Difficulty arbitrating between these systems, resulting in an over-reliance on one strategy over the other, has been implicated in compulsivity and extreme goal pursuit, both of which are observed in AN. Characterizing alterations in model-free and model-based systems, and their neural correlates, in AN may clarify mechanisms contributing to symptom heterogeneity (e.g., binge/purge symptoms). This study tested whether adolescents with restricting AN (AN-R; n = 36) and binge/purge AN (AN-BP; n = 20) differentially utilized model-based and model-free learning systems compared to a healthy control group (HC; n = 28) during a Markov two-step decision-making task under conditions of reward and punishment. Associations between model-free and model-based learning and resting-state functional connectivity between neural regions of interest, including orbitofrontal cortex (OFC), nucleus accumbens (NAcc), putamen, and sensory motor cortex (SMC) were examined. AN-R showed higher utilization of model-free learning compared to HC for reward, but attenuated model-free and model-based learning for punishment. In AN-R only, higher model-based learning was associated with stronger OFC-to-left NAcc functional connectivity, regions linked to goal-directed behavior. Greater utilization of model-free learning for reward in AN-R may differentiate this group, particularly during adolescence, and facilitate dietary restriction by prioritizing habitual control in rewarding contexts.

Brain Volume in Fetal Alcohol Spectrum Disorders Over a 20-Year Span.

Importance: Anomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD. Objective: To test whether brain tissue declines faster with aging in individuals with FASD compared with control participants. Design, Setting, and Participants: This cohort study used magnetic resonance imaging (MRI) data collected from individuals with FASD and control individuals (age 13-37 years at first magnetic resonance imaging [MRI1] acquired 1997-2000) compared with data collected 20 years later (MRI2; 2018-2021). Participants were recruited for MRI1 through the University of Washington Fetal Alcohol Syndrome (FAS) Follow-Up Study. For MRI2, former participants were recruited by the University of Washington Fetal Alcohol and Drug Unit. Data were analyzed from October 2022 to August 2023. Main Outcomes and Measures: Intracranial volume (ICV) and regional cortical and cerebellar gray matter, white matter, and cerebrospinal fluid volumes were quantified automatically and analyzed, with group and sex as between-participant factors and age as a within-participant variable. Results: Of 174 individuals with MRI1 data, 48 refused participation, 36 were unavailable, and 24 could not be located. The remaining 66 individuals (37.9%) were rescanned for MRI2, including 26 controls, 18 individuals with nondysmorphic heavily exposed fetal alcohol effects (FAE; diagnosed prior to MRI1), and 22 individuals with FAS. Mean (SD) age was 22.9 (5.6) years at MRI1 and 44.7 (6.5) years at MRI2, and 35 participants (53%) were male. The FAE and FAS groups exhibited enduring stepped volume deficits at MRI1 and MRI2; volumes among control participants were greater than among participants with FAE, which were greater than volumes among participants with FAS (eg, mean [SD] ICV: control, 1462.3 [119.3] cc at MRI1 and 1465.4 [129.4] cc at MRI2; FAE, 1375.6 [134.1] cc at MRI1 and 1371.7 [120.3] cc at MRI2; FAS, 1297.3 [163.0] cc at MRI1 and 1292.7 [172.1] cc at MRI2), without diagnosis-by-age interactions. Despite these persistent volume deficits, the FAE participants and FAS participants showed patterns of neurodevelopment within reference ranges: increase in white matter and decrease in gray matter of the cortex and decrease in white matter and increase in gray matter of the cerebellum. Conclusions and Relevance: The findings of this cohort study support a nonaccelerating enduring, brain structural dysmorphic spectrum following prenatal alcohol exposure and a diagnostic distinction based on the degree of dysmorphia. FASD was not a progressive brain structural disorder by middle age, but whether accelerated decline occurs in later years remains to be determined.

State-specific alterations in the neural computations underlying inhibitory control in women remitted from bulimia nervosa.

The neurocomputational processes underlying bulimia nervosa and its primary symptoms, out-of-control overeating and purging, are poorly understood. Research suggests that the brains of healthy individuals form a dynamic internal model to predict whether control is needed in each moment. This study tested the hypothesis that this computational process of inhibitory control is abnormally affected by metabolic state (being fasted or fed) in bulimia nervosa. A Bayesian ideal observer model was fit to behavioral data acquired from 22 women remitted from bulimia nervosa and 20 group-matched controls who completed a stop-signal task during two counterbalanced functional MRI sessions, one after a 16 h fast and one after a meal. This model estimates participants' trial-by-trial updating of the probability of a stop signal based on their experienced trial history. Neural analyses focused on control-related Bayesian prediction errors, which quantify the direction and degree of "surprise" an individual experiences on any given trial. Regardless of group, metabolic state did not affect behavioral performance on the task. However, metabolic state modulated group differences in neural activation. In the fed state, women remitted from bulimia nervosa had attenuated prediction-error-dependent activation in the left dorsal caudate. This fed-state activation was lower among women with more frequent past binge eating and self-induced vomiting. When they are in a fed state, individuals with bulimia nervosa may not effectively process unexpected information needed to engage inhibitory control. This may explain the difficulties these individuals have stopping eating after it begins.

Characterization of parent and youth-reported eating disorder symptoms and premorbid factors in the Adolescent Brain Cognitive Development Study.

Objective: Eating Disorders (EDs) often start in adolescence, though the prevalence, trajectory of symptom onset and predictors of illness are poorly understood, especially across sociodemographically diverse youth. Here, we leverage data from the Adolescent Brain Cognitive Development℠ (ABCD) Study, a large demographically representative longitudinal sample of youth in the US, to characterize the prevalence of parent- and youth-reported ED symptoms and their sociodemographic characteristics at baseline (ages 9-11) and two-years later (2-year; ages 11-14). Method: A tetrachoric factor analysis summarized clusters of ED symptoms, which were compared between parent and youth reports. Cognitive, mental and physical health variables at baseline were used to predict youth-reported symptoms at 2-year using a mixed-effects logistic regression. Results: Three factors emerged reflecting "weight distress", "weight control", and "bingeing", with prevalence rates ranging from 1.5 to 7.3%. All symptoms loaded on similar factors between reporters. Rates of symptom endorsement were similar for males and females, with disproportionately higher rates across factors for youth who self-identified as sexual minority, Hispanic, Black, or Mixed race participants, and those from a disadvantaged socioeconomic background, compared to the full ABCD sample. Youth and parent reports at 2-year showed ~17% overlap. A distinct pattern of cognitive variables emerged as significant predictors of later youth-reported ED concerns, whereas mental health symptoms and traits were non-specific and associated with all ED factors. Conclusion: Identifying the landscape of ED symptoms across demographic groups, reporters and their premorbid factors in late childhood is critical to inform prevention and early intervention efforts, with particularly important implications for historically understudied racial and sexual minority groups.

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Altered Reinforcement Learning from Reward and Punishment in Anorexia Nervosa: Evidence from Computational Modeling.

OBJECTIVES: Anorexia nervosa (AN) is associated with altered sensitivity to reward and punishment. Few studies have investigated whether this results in aberrant learning. The ability to learn from rewarding and aversive experiences is essential for flexibly adapting to changing environments, yet individuals with AN tend to demonstrate cognitive inflexibility, difficulty set-shifting and altered decision-making. Deficient reinforcement learning may contribute to repeated engagement in maladaptive behavior. METHODS: This study investigated learning in AN using a probabilistic associative learning task that separated learning of stimuli via reward from learning via punishment. Forty-two individuals with Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 restricting-type AN were compared to 38 healthy controls (HCs). We applied computational models of reinforcement learning to assess group differences in learning, thought to be driven by violations in expectations, or prediction errors (PEs). Linear regression analyses examined whether learning parameters predicted BMI at discharge. RESULTS: AN had lower learning rates than HC following both positive and negative PE (p < .02), and were less likely to exploit what they had learned. Negative PE on punishment trials predicted lower discharge BMI (p < .001), suggesting individuals with more negative expectancies about avoiding punishment had the poorest outcome. CONCLUSIONS: This is the first study to show lower rates of learning in AN following both positive and negative outcomes, with worse punishment learning predicting less weight gain. An inability to modify expectations about avoiding punishment might explain persistence of restricted eating despite negative consequences, and suggests that treatments that modify negative expectancy might be effective in reducing food avoidance in AN.

Prior Methamphetamine Use Disorder History Does Not Impair Interoceptive Processing of Soft Touch in HIV Infection.

INTRODUCTION: Interoception, defined as the sense of the internal state of one's body, helps motivate goal-directed behavior. Prior work has shown that methamphetamine (METH) use disorder is associated with altered interoception, and that this may contribute to risky behavior. As people with HIV (PWH) may also experience disrupted bodily sensations (e.g., neuropathy), an important question is whether PWH with a history of METH use disorder might exhibit greater impairment of interoceptive processing. METHODS: Eighty-three participants stratified by HIV infection and a past history of methamphetamine use disorder experienced a soft touch paradigm that included slow brush strokes on the left forearm and palm during blood-oxygen level-dependent functional MRI acquisition. To assess differences in interoception and reward, voxelwise analyses were constrained to the insula, a hub for the evaluation of interoceptive cues, and the striatum, which is engaged in reward processing. RESULTS: Overall, individuals with a history of METH use disorder had an attenuated neural response to pleasant touch in both the insula and striatum. Longer abstinence was associated with greater neural response to touch in the insula, suggesting some improvement in responsivity. However, only PWH with no METH use disorder history had lower brain activation in the insula relative to non-using seronegative controls. CONCLUSIONS: Our findings suggest that while METH use disorder history and HIV infection independently disrupt the neural processes associated with interoception, PWH with METH use disorder histories do not show significant differences relative to non-using seronegative controls. These findings suggest that the effects of HIV infection and past methamphetamine use might not be additive with respect to interoceptive processing impairment.

Satiety does not alter the ventral striatum's response to immediate reward in bulimia nervosa.

Individuals with bulimia nervosa (BN) cycle between periods of binge-eating and compensatory behavior and periods of dietary restraint, suggesting extremes of under and overcontrol that may be metabolic-state related. This study examined the influence of hunger and satiety on impulsivity and neural responding during decision-making. Twenty-three women remitted from BN (RBN) and 20 healthy comparison women (CW) performed a delay discounting task after a 16-hr fast and following a standardized meal during functional neuroimaging. A dual-systems approach examined reward valuation (decision trials where the early reward option was available immediately) and cognitive control (all decision trials). Interactions of Group × Visit (Hungry, Fed) for immediate reward revealed that CW had greater activation when hungry versus fed in the ventral striatum and dorsal caudate, whereas RBN had greater response when fed versus hungry in the dorsal caudate. Compared to CW, RBN showed decreased response when hungry within the left dorsal caudate and ventral striatum and increased response when fed in bilateral dorsal caudate. No differences were found within cognitive control regions or with choice behavior. Reward sensitivity is normally increased when hungry and decreased when fed; our findings in CW provide further support of hunger-based reward sensitivity within the striatum. However, RBN showed no differences for hunger and satiety in the ventral striatum and greater activation in the dorsal caudate when fed compared to hungry. This suggests RBN may be less sensitive to reward when hungry but do not devalue reward when satiated, indicating altered metabolic modulation of self-regulatory control. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Increased anticipatory brain response to pleasant touch in women remitted from bulimia nervosa.

Bulimia nervosa (BN) is characterized by affective instability and dysregulated behaviors (binge eating, fasting, self-induced vomiting) that disrupt bodily homeostasis. Mechanisms underlying dysregulation in BN are unclear, although altered reward responsivity, anticipatory processing of environmental cues, and interoception (detection and integration of body-state signals to regulate behavior) have been implicated in BN pathophysiology. We aimed to determine whether BN is associated with ineffectively predicting body state or integrating predicted experience with actual experience by examining neural response to anticipation and experience of affective touch, a pleasant interoceptive stimulus that acts on sensory and emotional systems to guide behavior. During fMRI, we administered soft strokes to the palm and forearm in women remitted from BN (RBN; N = 23) and control women (CW; N = 25). A Group (RBN/CW) × Condition (anticipation/touch) interaction was found in the right dorsal caudate; both CW and RBN had increased activation during touch compared with anticipation, with RBN demonstrating marginally greater anticipatory response than CW. For RBN, those individuals who showed greater anticipatory response in the dorsal caudate also reported higher levels of harm avoidance. RBN individuals relative to CW showed greater activation in left putamen and insula during the anticipation but not when experiencing an affective touch. This increase during anticipation rather than the actual experience of the affective touch is consistent with a top-down preparatory process which is associated with harm avoidance and is similar to what has been observed in anxious individuals. This aberrant signal integration could disrupt feedback processing, serving to maintain disordered behavior.

Associations Between Body Weight, Hippocampal Volume, and Tissue Signal Intensity in 12- to 18-Year-Olds.

OBJECTIVE: The hippocampus is a key structure in feeding behaviors and weight regulation. Obesity may lead to disruptions in hippocampal structure. In animals, obesity-related factors (e.g., high-fat/sugar foods) are associated with hippocampal insult (e.g., alterations in the blood brain barrier). In humans, individuals with obesity, relative to healthy weight, have smaller hippocampal volumes. Few studies have examined the association between body weight and the hippocampus during adolescence, a critical brain development period. This study examined hippocampal volume and tissue signal intensity in adolescents across the weight spectrum. METHODS: Structural magnetic resonance imaging and anthropomorphic data were available for 102 12- to 18-year-old adolescents (53% female; 15.07 [SD 1.84] years; standardized BMI [BMIz] scores using the Centers for Disease Control and Prevention growth charts: 0.54 [SD 1.17]) from the Pediatric Imaging, Neurocognition, and Genetics database. Linear regression models controlling for age, sex, genetic ancestry, scanner, and household income examined the relationship between BMIz, hippocampal volume, and T2-weighted hippocampal signal intensity. RESULTS: BMIz was negatively associated with T2-weighted hippocampal signal intensity in the left (t = -3.05; P = 0.003; r = -0.21) and right (t = -2.50; P = 0.01; r = -0.36) hippocampi. BMIz was not significantly associated with hippocampal volume. CONCLUSIONS: BMIz is associated with hippocampal tissue characteristics during adolescence, which could impact later brain development.

Neural Insensitivity to the Effects of Hunger in Women Remitted From Anorexia Nervosa.

OBJECTIVE: Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This study's aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa. METHODS: At two scanning sessions scheduled 24 hours apart, one after a 16-hour fast and one after a standardized meal, 26 women who were in remission from anorexia nervosa (to avoid the confounding effects of malnutrition) and 22 matched control women received tastes of sucrose solution or ionic water while functional MRI data were acquired. Within a network of interest responsible for food valuation and transforming taste signals into motivation to eat, the authors compared groups across conditions on blood-oxygen-level-dependent (BOLD) signal and task-based functional connectivity. RESULTS: Participants in the two groups had similar BOLD responses to sucrose and water tastants. A group-by-condition interaction in the ventral caudal putamen indicated that hunger had opposite effects on tastant response in the control group and the remitted anorexia nervosa group, with an increase and a decrease, respectively, in BOLD response when hungry. Hunger had a similar opposite effect on insula-to-ventral caudal putamen functional connectivity in the remitted anorexia nervosa group compared with the control group. Exploratory analyses indicated that lower caudate response to tastants when hungry was associated with higher scores on harm avoidance among participants in the remitted anorexia nervosa group. CONCLUSIONS: Reduced recruitment of neural circuitry that translates taste stimulation to motivated eating behavior when hungry may facilitate food avoidance and prolonged periods of extremely restricted food intake in anorexia nervosa.

Neurodevelopment in adolescents and adults with fetal alcohol spectrum disorders (FASD): A magnetic resonance region of interest analysis.

The neurodevelopmental trajectory in individuals with fetal alcohol spectrum disorders (FASD) has not been well characterized. We examined age-related differences in the volume of the corpus callosum, basal ganglia, and cerebellum across adolescence and young adulthood, due to the sensitivity of these regions to prenatal alcohol exposure. T1-weighted anatomical magnetic resonance images (MRI) were acquired from a cross-sectional sample of subjects 13-30 years old who had received an alcohol-related diagnosis (FASD, n = 107) and typically developing controls (CON, n = 56). FreeSurfer v5.3 was used to obtain volumetric data for the corpus callosum, caudate, putamen, pallidum, and cerebellum. Analysis of variance (ANOVA) was used to examine the effects of group (FASD, CON), sex, and age on region volume. Data were analyzed with and without correction for intracranial volume (ICV). All subregions were significantly smaller in the FASD group compared to controls, and these findings persisted even after ICV correction. Furthermore, the FASD and control groups differed in their relationship between age and total volume of the corpus callosum, caudate, and cerebellum. Specifically, older FASD individuals had smaller total volume in these regions; this relationship was not seen in the control group. Control males demonstrated larger volumes than control females in all regions prior to ICV correction; however, sex differences were attenuated in the FASD group in both the pallidum and cerebellum. Sex differences remained after ICV correction in the pallidum and cerebellum. These cross-sectional findings suggest that at least some brain regions may become smaller at an earlier than expected age in individuals with FASD, and that sex is an important factor to consider when examining neural structures in FASD. Further evaluation is necessary using longitudinal methods and including older ages.

Altered anticipation and processing of aversive interoceptive experience among women remitted from bulimia nervosa.

Bulimia nervosa (BN) is characterized by dysregulated intake of food, which may indicate homeostatic imbalance. Critically important for homeostatic regulation is interoception, or the sensing and processing of body-relevant information. A well-documented link between avoidance of unpleasant body sensations and BN symptoms suggests that aversive interoceptive experiences may be particularly relevant to BN pathophysiology. This study examined whether individuals with a history of BN show aberrant neural processing of aversive interoceptive stimuli. Using a cued inspiratory breathing load paradigm, we compared women remitted from BN (RBN; n = 24; to reduce the confounding effects of active bulimic symptoms) and control women (CW; n = 25). During breathing load anticipation, the RBN group, relative to CW, showed increased activation in mid-insula, superior frontal gyrus, putamen, dorsal anterior cingulate, posterior cingulate, and amygdala. However, over the course of the aversive experience, neural activation in RBN relative to CW showed an aberrant decline in most of these regions. Exploratory analyses indicated that greater activation during breathing load anticipation was associated with past bulimic symptom severity and the duration of symptom remission. An exaggerated anticipatory response and an abnormally decreasing response during aversive homeostatic perturbations may promote hallmark bulimic behaviors-binge eating, dietary restriction, and purging. Our findings support a role for homeostatic instability in BN, and these altered patterns of brain activation may serve as novel targets for pharmacological, neuromodulatory, and behavioral interventions.

Neural hypersensitivity to pleasant touch in women remitted from anorexia nervosa.

Interoception, or the sensing and integration of bodily state signals, has been implicated in anorexia nervosa (AN), given that the hallmark symptoms involve food restriction and body image disturbance. Here we focus on brain response to the anticipation and experience of affective interoceptive stimuli. Women remitted from AN (RAN; N = 18) and healthy comparison women (CW; N = 26) underwent a pleasant affective touch paradigm consisting of gentle strokes with a soft brush administered to the forearm or palm during functional neuroimaging. RAN had a lower brain response relative to CW during anticipation of touch, but a greater response when experiencing touch in the right ventral mid-insula. In RAN, this reduced anticipatory response was associated with higher levels of harm avoidance. Exploratory analyses in RAN also suggested that lower response during touch anticipation was associated with greater body dissatisfaction and higher perceived touch intensity ratings. This reduced responsivity to the anticipation of pleasant affective interoceptive stimuli in association with higher harm avoidance, along with an elevated response to the experience of touch, suggests an impaired ability in AN to predict and interpret incoming physiological stimuli. Impaired interoception may thus impact one's sense of self, thereby supporting observations of disturbed body image and avoidance of affective and social stimuli. Therapeutic approaches that help AN to better anticipate and interpret salient affective stimuli or improve tolerance of interoceptive experiences may be an important addition to current interventions.

Altered functional connectivity during spatial working memory in children with heavy prenatal alcohol exposure.

Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n = 18) and controls (CON group; n = 19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p = 0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < 0.05. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure.

Aberrant Cerebral Blood Flow in Response to Hunger and Satiety in Women Remitted from Anorexia Nervosa.

The etiology of pathological eating in anorexia nervosa (AN) remains poorly understood. Cerebral blood flow (CBF) is an indirect marker of neuronal function. In healthy adults, fasting increases CBF, reflecting increased delivery of oxygen and glucose to support brain metabolism. This study investigated whether women remitted from restricting-type AN (RAN) have altered CBF in response to hunger that may indicate homeostatic dysregulation contributing to their ability to restrict food. We compared resting CBF measured with pulsed arterial spin labeling in 21 RAN and 16 healthy comparison women (CW) when hungry (after a 16-h fast) and after a meal. Only remitted subjects were examined to avoid the confounding effects of malnutrition on brain function. Compared to CW, RAN demonstrated a reduced difference in the Hungry - Fed CBF contrast in the right ventral striatum, right subgenual anterior cingulate cortex (pcorr < 0.05) and left posterior insula (punc < 0.05); RAN had decreased CBF when hungry versus fed, whereas CW had increased CBF when hungry versus fed. Moreover, decreased CBF when hungry in the left insula was associated with greater hunger ratings on the fasted day for RAN. This represents the first study to show that women remitted from AN have aberrant resting neurovascular function in homeostatic neural circuitry in response to hunger. Regions involved in homeostatic regulation showed group differences in the Hungry - Fed contrast, suggesting altered cellular energy metabolism in this circuitry that may reduce motivation to eat.

Response in taste circuitry is not modulated by hunger and satiety in women remitted from bulimia nervosa.

Individuals with bulimia nervosa (BN) engage in episodes of binge eating, marked by loss of control and eating despite fullness. Does altered reward and metabolic state contribute to BN pathophysiology? Normally, hunger increases (and satiety decreases) reward salience to regulate eating. We investigated whether BN is associated with an abnormal response in a neural circuit involved in translating taste signals into motivated behavior, when hungry and fed. Twenty-six women remitted from BN (RBN) and 22 control women (CW) were administered water and sucrose during 2 counterbalanced fMRI visits, following a 16-hr fast or a standardized breakfast. Significant Group × Condition interactions were found in the left putamen, insula, and amygdala. Post hoc analyses revealed CW were significantly more responsive to taste stimuli when hungry versus fed in the left putamen and amygdala. In contrast, RBN response did not differ between conditions. Further, RBN had greater activation in the left amygdala compared with CW when fed. Findings suggest that RBN neural response to rewarding stimuli may not be modulated by metabolic state. Data raise the possibility that disinhibited eating in BN could result from a failure to devalue food reward when fed, resulting in an exaggerated response. (PsycINFO Database Record

Altered reward expectancy in individuals with recent methamphetamine dependence.

BACKGROUND: Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine-dependent individuals show heightened reactivity to positively valenced stimuli (i.e. positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e. driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH-) histories of methamphetamine dependence. METHODS: Participants (17 METH+; 23 METH-) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. RESULTS: METH+ had less BOLD response to loss anticipation than METH- in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH- did not show differential responses to the valence of outcomes. DISCUSSION: METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior.

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models.

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value.