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.

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.

Striatal and Pallidal Activation during Reward Modulated Movement Using a Translational Paradigm.

Human neuroimaging studies of reward processing typically involve tasks that engage decision-making processes in the dorsal striatum or focus upon the ventral striatum's response to feedback expectancy. These studies are often compared to the animal literature; however, some animal studies include both feedback and nonfeedback events that activate the dorsal striatum during feedback expectancy. Differences in task parameters, movement complexity, and motoric effort to attain rewards may partly explain ventral and dorsal striatal response differences across species. We, therefore, used a target capture task during functional neuroimaging that was inspired by a study of single cell modulation in the internal globus pallidus during reward-cued, rotational arm movements in nonhuman primates. In this functional magnetic resonance imaging study, participants used a fiberoptic joystick to make a rotational response to an instruction stimulus that indicated both a target location for a capture movement and whether or not the trial would end with feedback indicating either a small financial gain or a neutral outcome. Portions of the dorsal striatum and pallidum demonstrated greater neural activation to visual cues predicting potential gains relative to cues with no associated outcome. Furthermore, both striatal and pallidal regions displayed a greater response to financial gains relative to neutral outcomes. This reward-dependent modulation of dorsal striatal and pallidal activation in a target-capture task is consistent with findings from reward studies in animals, supporting the use of motorically complex tasks as translational paradigms to investigate the neural substrates of reward expectancy and outcome in humans.

HIV infection is associated with attenuated frontostriatal intrinsic connectivity: a preliminary study.

HIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the association of HIV infection with functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Fifteen HIV-positive and 15 demographically matched control participants underwent 6 min of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). HIV - associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (<50 years, N=9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was also associated with reduced frontostriatal connectivity. In conclusion, our data indicate that HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies.

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.

Sociodemographic correlates of parent and youth-reported eating disorder symptoms in the Adolescent Brain Cognitive Development Study.

PURPOSE: Eating Disorders (EDs) often start in adolescence, though ED-related concerns in diverse youth samples remain understudied. We leveraged data from the Adolescent Brain Cognitive Development (ABCD) Study to identify the prevalence of parent- and youth-reported ED symptoms and their sociodemographic characteristics. METHODS: Data were drawn from baseline (ages 9-11 years, n=11,868) and 2-year follow-up (ages 11-14 years; n=10,908) from the ABCD Study. A tetrachoric factor analysis summarized clusters of ED symptoms, which were compared between parent and youth reports and across sociodemographic variables. RESULTS: Three factors emerged reflecting "weight distress", "weight control", and "binge eating" (prevalence range: 1.5-7.3%). Symptoms loaded onto similar factors between reporters. Rates of symptom endorsement were similar between sexes, with disproportionately higher endorsement rates for youth who self-identified as sexual minority, Hispanic, Black, or Mixed race participants, and those from a disadvantaged socioeconomic background, compared to the reference ABCD sample. Youth and parent reports at 2-year showed ~12% overlap. CONCLUSIONS: ED-related concerns among historically understudied racial and sexual minority groups call for greater attention to the detection and treatment of these symptoms in these groups. Applying a transdiagnostic approach to ED symptoms can inform effective detection and intervention efforts.

Alterations in white matter microstructure in women recovered from anorexia nervosa.

OBJECTIVE: A recent study of ill individuals with anorexia nervosa (AN) reported microstructural alterations in white matter integrity including lower fractional anisotropy and higher mean diffusivity. This study was designed to determine whether such alterations exist in long-term recovered AN individuals and to examine potential associations with underlying AN traits. METHOD: Twelve adult women recovered from restricting-type AN and 10 control women were studied using diffusion tensor imaging. RESULTS: Overall, there was no significant fractional anisotropy alteration in recovered AN, in contrast to a prior study reporting lower fractional anisotropy in ill AN. Further, recovered AN showed lower mean diffusivity in frontal, parietal and cingulum white matter relative to control women, contrary to elevated mean diffusivity previously reported in ill AN. Lower longitudinal diffusivity in recovered AN was associated with higher harm avoidance. However, more severe illness history was associated with worse white matter integrity after recovery in the same direction as reported in prior work. DISCUSSION: Our findings suggest that fractional anisotropy in recovered AN is not different from controls, however, a novel pattern of lower mean diffusivity was evidenced in recovered AN, and this alteration was associated with harm avoidance. Notably, severity of illness history may have long-term consequences, emphasizing the importance of aggressive treatment.

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.

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.

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).

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.

Altered striatal response to reward in bulimia nervosa after recovery.

OBJECTIVE: It is possible that disturbances of systems modulating reward may contribute to a vulnerability to develop an eating disorder. METHOD: This hypothesis was tested by assessing functional magnetic resonance brain imaging response to a monetary reward task known to activate the anterior ventral striatum (AVS), a region implicated in motivational aspects toward stimuli. To avoid the confounding effects of malnutrition, 10 women who had recovered from bulimia nervosa (BN) were compared with 10 healthy comparison women (CW). RESULTS: For the AVS, CW distinguished positive and negative feedback, whereas recovered BN women had similar responses to both conditions. In addition, these groups had similar patterns of findings for the dorsal caudate. DISCUSSION: We have previously shown that individuals recovered from anorexia nervosa (AN) also had altered striatal responses and difficulties in differentiating positive and negative feedback. Thus BN and AN individuals may share a difficulty in discriminating the emotional significance of a stimulus.

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.

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.

The influence of feedback valence in associative learning.

The neural systems engaged by intrinsic positive or negative feedback were defined in an associative learning task. Through trial and error, participants learned the arbitrary assignments of a set of stimuli to one of two response categories. Informative feedback was provided on less than 25% of the trials. During positive feedback blocks, half of the trials were eligible for informative feedback; of these, informative feedback was only provided when the response was correct. A similar procedure was used on negative feedback blocks, but here informative feedback was only provided when the response was incorrect. In this manner, we sought to identify regions that were differentially responsive to positive and negative feedback as well as areas that were responsive to both types of informative feedback. Several regions of interest, including the bilateral nucleus accumbens, caudate nucleus, anterior insula, right cerebellar lobule VI, and left putamen, were sensitive to informative feedback regardless of valence. In contrast, several regions were more selective to positive feedback compared to negative feedback. These included the insula, amygdala, putamen, and supplementary motor area. No regions were more strongly activated by negative feedback compared to positive feedback. These results indicate that the neural areas supporting associative learning vary as a function of how that information is learned. In addition, areas linked to intrinsic reinforcement showed considerable overlap with those identified in studies using extrinsic reinforcers.

Tuning in to the voices: a multisite FMRI study of auditory hallucinations.

INTRODUCTION: Auditory hallucinations or voices are experienced by 75% of people diagnosed with schizophrenia. We presumed that auditory cortex of schizophrenia patients who experience hallucinations is tonically "tuned" to internal auditory channels, at the cost of processing external sounds, both speech and nonspeech. Accordingly, we predicted that patients who hallucinate would show less auditory cortical activation to external acoustic stimuli than patients who did not. METHODS: At 9 Functional Imaging Biomedical Informatics Research Network (FBIRN) sites, whole-brain images from 106 patients and 111 healthy comparison subjects were collected while subjects performed an auditory target detection task. Data were processed with the FBIRN processing stream. A region of interest analysis extracted activation values from primary (BA41) and secondary auditory cortex (BA42), auditory association cortex (BA22), and middle temporal gyrus (BA21). Patients were sorted into hallucinators (n = 66) and nonhallucinators (n = 40) based on symptom ratings done during the previous week. RESULTS: Hallucinators had less activation to probe tones in left primary auditory cortex (BA41) than nonhallucinators. This effect was not seen on the right. DISCUSSION: Although "voices" are the anticipated sensory experience, it appears that even primary auditory cortex is "turned on" and "tuned in" to process internal acoustic information at the cost of processing external sounds. Although this study was not designed to probe cortical competition for auditory resources, we were able to take advantage of the data and find significant effects, perhaps because of the power afforded by such a large sample.

Brain-performance correlates of working memory retrieval in schizophrenia: a cognitive modeling approach.

Correlations of cognitive functioning with brain activation during a sternberg item recognition paradigm (SIRP) were investigated in patients with schizophrenia and in healthy controls studied at 8 sites. To measure memory scanning times, 4 response time models were fit to SIRP data. The best fitting model assumed exhaustive serial memory scanning followed by self-terminating memory search and involved one intercept parameter to represent SIRP processes not contributing directly to memory scanning. Patients displayed significantly longer response times with increasing memory load and differed on the memory scanning, memory search, and intercept parameters of the best fitting probability model. Groups differed in the correlation between the memory scanning parameter and linear brain response to increasing memory load within left inferior and left middle frontal gyrus, bilateral caudate, and right precuneus. The pattern of findings in these regions indicated that high scanning capacity was associated with high neural capacity among healthy subjects but that scanning speed was uncoupled from brain response to increasing memory load among schizophrenia patients. Group differences in correlation of the best fitting model's scanning parameter with a quadratic trend in brain response to increasing memory load suggested inefficient or disordered patterns of neural inhibition among individuals with schizophrenia, especially in the left perirhinal and entorhinal cortices. The results show at both cognitive and neural levels that disordered memory scanning contributes to deficient SIRP performance among schizophrenia patients.

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.