Fasting biases brain reward systems towards high-calorie foods

Nutritional state (e.g. fasted vs. fed) and different food stimuli (e.g. high-calorie vs. low-calorie, or appetizing vs. bland foods) are both recognized to change activity in brain reward systems. Using functional magnetic resonance imaging, we have studied the interaction between nutritional state and different food stimuli on brain food reward systems. We examined how blood oxygen level-dependent activity within a priori regions of interest varied while viewing pictures of high-calorie and low-calorie foods. Pictures of non-food household objects were included as control stimuli. During scanning, subjects rated the appeal of each picture. Twenty non-obese healthy adults [body mass index 22.1 ± 0.5 kg/m² (mean ± SEM), age range 19–35 years, 10 male] were scanned on two separate mornings between 11:00 and 12:00 h, once after eating a filling breakfast ('fed': 1.6 ± 0.1 h since breakfast), and once after an overnight fast but skipping breakfast ('fasted': 15.9 ± 0.3 h since supper) in a randomized cross-over design. Fasting selectively increased activation to pictures of high-calorie over low-calorie foods in the ventral striatum, amygdala, anterior insula, and medial and lateral orbitofrontal cortex (OFC). Furthermore, fasting enhanced the subjective appeal of high-calorie more than low-calorie foods, and the change in appeal bias towards high-calorie foods was positively correlated with medial and lateral OFC activation. These results demonstrate an interaction between homeostatic and hedonic aspects of feeding behaviour, with fasting biasing brain reward systems towards high-calorie foods.     

Weight gain following subthalamic nucleus deep brain stimulation: A PET study

Several hypotheses have been put forward to explain weight gain after deep brain stimulation (DBS), but none provides a fully satisfactory account of this adverse effect. We analyzed the correlation between changes in brain metabolism (using positron emission tomography [PET] imaging) and weight gain after bilateral subthalamic nucleus DBS in patients with Parkinson's disease. Body mass index was calculated and brain activity prospectively measured using 2‐deoxy‐2[18F]fluoro‐D ‐glucose 3 months before and 4 months after the start of subthalamic nucleus deep brain stimulation in 23 patients with Parkinson's disease. Motor complications (United Parkinson's Disease Rating Scale [UPDRS]‐IV scores) and dopaminergic medication were included in the analysis to control for their possible influence on brain metabolism. Mean ± standard deviation (SD) body mass index increased significantly by 0.8 ± 1.5 kg/m² (P = 0.03). Correlations were found between weight gain and changes in brain metabolism in limbic and associative areas, including the orbitofrontal cortex (Brodmann areas [BAs] 10 and 11), lateral and medial parts of the temporal lobe (BAs 20, 21, 22,39 and 42), anterior cingulate cortex (BA 32), and retrosplenial cortex (BA 30). However, we found no correlation between weight gain and metabolic changes in sensorimotor areas. These findings suggest that changes in associative and limbic processes contribute to weight gain after subthalamic nucleus DBS in Parkinson's disease. © 2014 International Parkinson and Movement Disorder Society     

An obesity‐associated risk allele within the FTO gene affects human brain activity for areas important for emotion,impulse control and reward in response to food images

Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight‐loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low‐ or high‐calorie food while brain activity was measured via fMRI. In a whole‐brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non‐risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.     

More restriction,more overeating: conflict monitoring ability is impaired by food-thought suppression among restrained eaters

Numerous studies have shown that restrained eating is not an effective weight loss strategy. Restrained eaters often suppress their desires and thoughts about tasty food, which makes it more difficult to control themselves in subsequent eating behavior. The ego depletion impairs conflict monitoring abilities. Therefore, this study explored the effects of food thoughts suppression on restrained eaters’ conflict monitoring. Therefore, this study used functional magnetic resonance imaging (fMRI) methods to explore changes in the activity of brain regions involved in conflict monitoring when restrained eaters choose between high- and low-calorie foods after either suppressing or not suppressing thoughts about food. The results showed that, compared to the control condition, after suppression of such thoughts, restrained eaters chose more high-calorie foods and displayed decreased activity in the dorsal anterior cingulate cortex—an important region in charge of conflict monitoring. At the same time, the functional coupling of the dorsal anterior cingulate cortex and the precuneus increased. Our findings suggest that restrained eaters’ suppression of thoughts about tasty food could lead to a decline in their ability to monitor conflicts between current behaviors and goals, which in turn leads to unhealthy eating behavior.

     

Different representations of pleasant and unpleasant odours in the human brain

Odours are important in emotional processing; yet relatively little is known about the representations of the affective qualities of odours in the human brain. We found that three pleasant and three unpleasant odours activated dissociable parts of the human brain. Pleasant but not unpleasant odours were found to activate a medial region of the rostral orbitofrontal cortex. Further, there was a correlation between the subjective pleasantness ratings of the six odours given during the investigation with activation of a medial region of the rostral orbitofrontal cortex. In contrast, a correlation between the subjective unpleasantness ratings of the six odours was found in regions of the left and more lateral orbitofrontal cortex. Moreover, a double dissociation was found with the intensity ratings of the odours, which were not correlated with the BOLD signal in the orbitofrontal cortex, but were correlated with the signal in medial olfactory cortical areas including the pyriform and anterior entorhinal cortex. Activation was also found in the anterior cingulate cortex, with a middle part of the anterior cingulate activated by both pleasant and unpleasant odours, and a more anterior part of the anterior cingulate cortex showing a correlation with the subjective pleasantness ratings of the odours. Thus the results suggest that there is a hedonic map of the sense of smell in brain regions such as the orbitofrontal cortex, and these results have implications for understanding the psychiatric and related problems that follow damage to these brain areas.     

A pilot study of functional magnetic resonance imaging brain correlates of deception in healthy young men

We hypothesized that specific brain regions would activate during deception, and these areas would correlate with changes in electrodermal activity (EDA). Eight men were asked to find money hidden under various objects. While functional MRI images were acquired and EDA was recorded, the subjects gave both truthful and deceptive answers regarding the money's location. The group analysis revealed significant activation during deception in the orbitofrontal cortex (OFCx) and anterior cingulate (AC), but individual results were not consistent. Individually and as a group, EDA correlated with blood flow changes in the OFCx and AC. Specific brain regions were activated during deception, but the present technique lacks good predictive power for individuals.     

Functional connectivity with anterior cingulate and orbitofrontal cortices during decision-making

Recent neuroscience research is beginning to discover the brain regions involved in decision-making under uncertainty, but little is known about whether or how these regions functionally interact with each other. Here, we used event-related functional magnetic resonance imaging to examine both changes in overall activity and changes in functional connectivity during risk-taking. Results showed that choosing high-risk over low-risk decisions was associated with increased activity in both anterior cingulate and orbitofrontal cortices. Connectivity analyses revealed that largely distinct, but somewhat overlapping, cortical and subcortical regions exhibited significant functional connectivity with anterior cingulate and orbitofrontal cortices. Additionally, connectivity with the anterior cingulate in some regions, including the orbitofrontal cortex and nucleus accumbens, was modulated by the decision participants chose. These findings (1) elucidate large networks of brain regions that are functionally connected with both anterior cingulate and orbitofrontal cortices during decision-making and (2) demonstrate that the roles of orbitofrontal and anterior cingulate cortices can be functionally differentiated by examining patterns of connectivity.     

Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study.

BACKGROUND: Patients with bipolar disorder have been reported to have abnormal cortical function during mania. In this study, we sought to investigate neural activity in the frontal lobe during mania, using functional magnetic resonance imaging (fMRI). Specifically, we sought to evaluate activation in the lateral orbitofrontal cortex, a brain region that is normally activated during activities that require response inhibition. METHODS: Eleven manic subjects and 13 control subjects underwent fMRI while performing the Go-NoGo task, a neuropsychological paradigm known to activate the orbitofrontal cortex in normal subjects. Patterns of whole-brain activation during fMRI scanning were determined with statistical parametric mapping. Contrasts were made for each subject for the NoGo minus Go conditions. Contrasts were used in a second-level analysis with subject as a random factor. RESULTS: Functional MRI data revealed robust activation of the right orbitofrontal cortex (Brodmann's area [BA] 47) in control subjects but not in manic subjects. Random-effects analyses demonstrated significantly less magnitude in signal intensity in the right lateral orbitofrontal cortex (BA 47), right hippocampus, and left cingulate (BA 24) in manic compared with control subjects. CONCLUSIONS: Mania is associated with a significant attenuation of task-related activation of right lateral orbitofrontal function. This lack of activation of a brain region that is usually involved in suppression of responses might account for some of the disinhibition seen in mania. In addition, hippocampal and cingulate activation seem to be decreased. The relationship between this reduced function and the symptoms of mania remain to be further explored.     

Effective connectivity of a reward network in obese women

Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used functional magnetic resonance imaging (fMRI) to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdala's modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortex's modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a food's reward value or an associated cue's motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals.     

Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.     

Neural dynamics of rejection sensitivity

Rejection sensitivity (RS) is the tendency to anxiously expect, readily perceive, and intensely react to rejection. This study used functional magnetic resonance imaging to explore whether individual differences in RS are mediated by differential recruitment of brain regions involved in emotional appraisal and/or cognitive control. High and low RS participants were scanned while viewing either representational paintings depicting themes of rejection and acceptance or nonrepresentational control paintings matched for positive or negative valence, arousal and interest level. Across all participants, rejection versus acceptance images activated regions of the brain involved in processing affective stimuli (posterior cingulate, insula), and cognitive control (dorsal anterior cingulate cortex; medial frontal cortex). Low and high RS individuals' responses to rejection versus acceptance images were not, however, identical. Low RS individuals displayed significantly more activity in left inferior and right dorsal frontal regions, and activity in these areas correlated negatively with participants' self-report distress ratings. In addition, control analyses revealed no effect of viewing negative versus positive images in any of the areas described above, suggesting that the aforementioned activations were involved in rejection-relevant processing rather than processing negatively valenced stimuli per se. Taken together, these findings suggest that responses in regions traditionally implicated in emotional processing and cognitive control are sensitive to rejection stimuli irrespective of RS, but that low RS individuals may activate prefrontal structures to regulate distress associated with viewing such images.     

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study.

BACKGROUND: Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. METHODS: Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. RESULTS: We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. CONCLUSIONS: While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.     

Local glutamate in cingulate cortex subregions differentially correlates with affective network activations during face perception

The cingulate cortex is involved in emotion recognition/perception and regulation. Rostral and caudal subregions belong to different brain networks with distinct roles in affective perception. Despite recent accounts of the relevance of cingulate cortex glutamate (Glu) on blood‐oxygen‐level‐dependent (BOLD) responses, the specificity of the subregional Glu levels during emotional tasks remains unclear. Seventy‐two healthy participants (age = 27.33 ± 6.67, 32 women) performed an affective face‐matching task and underwent magnetic resonance spectroscopy (MRS) at 7 Tesla. Correlations between the BOLD response during emotion perception and Glu concentration in the pregenual anterior cingulate cortex (pgACC) and anterior midcingulate cortex (aMCC) were compared on a whole‐brain level. Post hoc specificity of the association with an affect was assessed. Lower Glu in the pgACC correlated with stronger activation differences between negative and positive faces in the left inferior and superior frontal gyrus (L IFG and L SFG). In contrast, lower Glu in the aMCC correlated with BOLD contrasts in the posterior cingulate cortex (PCC). Furthermore, negative face detection was associated with prolonged response time (RT). Our results demonstrate a subregion‐specific involvement of cingulate cortex Glu in interindividual differences during viewing of affective facial expressions. Glu levels in the pgACC were correlated with frontal area brain activations, whereas Glu in the salience network component aMCC modulated responses in the PCC–precuneus. We show that region‐specific metabolite mapping enables specific activation of different BOLD signals in the brain underlying emotional perception.     

Acute after-school screen time in children decreases impulse control and activation toward high-calorie food stimuli in brain regions related to reward and attention

The purpose of this study was to examine the effects of after-school sedentary screen time on children’s brain activation in reward and cognitive control regions in response to pictures of high- and low-calorie foods. Thirty-two children participated in a randomized crossover study with counterbalanced treatment conditions. Conditions took place on separate days after school and included three hours of active or sedentary play. After each condition, neural activation was assessed using functional magnetic resonance imaging (fMRI) while participants completed a go/no-go task involving pictures of high- and low-calorie foods. General response inhibition was also measured using the Stroop task. Hunger was measured upon arrival to the testing facility and just prior to fMRI scans. Mixed effects models were used to evaluate main effects and interactions. Significant stimulus by condition interactions were found in the right superior parietal cortex, and left anterior cingulate cortex (Ps?≤?0.05). High-calorie pictures elicited significantly more activation bilaterally in the orbitofrontal cortex compared to low-calorie pictures (Ps?≤?0.05). Stroop task performance diminished significantly following the sedentary condition compared to the active (P?≤?0.05). Subjective feelings of hunger were not different between conditions at any point. Sedentary screen time was associated with significantly decreased response inhibition and a reversed brain activation pattern to pictures of high- and low-calorie foods compared to active play, in areas of the brain important to the modulation of food intake. Decreased attention, and impulse control following sedentary screen time may contribute to disinhibited eating that can lead to overweight and obesity.

     

The obese brain: association of body mass index and insulin sensitivity with resting state network functional connectivity

Obesity is a key risk factor for the development of insulin resistance, Type 2 diabetes and associated diseases; thus, it has become a major public health concern. In this context, a detailed understanding of brain networks regulating food intake, including hormonal modulation, is crucial. At present, little is known about potential alterations of cerebral networks regulating ingestive behavior. We used "resting state" functional magnetic resonance imaging to investigate the functional connectivity integrity of resting state networks (RSNs) related to food intake in lean and obese subjects using independent component analysis. Our results showed altered functional connectivity strength in obese compared to lean subjects in the default mode network (DMN) and temporal lobe network. In the DMN, obese subjects showed in the precuneus bilaterally increased and in the right anterior cingulate decreased functional connectivity strength. Furthermore, in the temporal lobe network, obese subjects showed decreased functional connectivity strength in the left insular cortex. The functional connectivity magnitude significantly correlated with body mass index (BMI). Two further RSNs, including brain regions associated with food and reward processing, did not show BMI, but insulin associated functional connectivity strength. Here, the left orbitofrontal cortex and right putamen functional connectivity strength was positively correlated with fasting insulin levels and negatively correlated with insulin sensitivity index. Taken together, these results complement and expand previous functional neuroimaging findings by demonstrating that obesity and insulin levels influence brain function during rest in networks supporting reward and food regulation.     

Brain activation during the perception of stressful word stimuli concerning interpersonal relationships in anorexia nervosa patients with high degrees of alexithymia in an fMRI paradigm

Several studies have reported that anorexia nervosa (AN) patients have high levels of alexithymia. However, relatively little is known about the underlying neurobiological relationships between alexithymia and AN. We used functional magnetic resonance imaging to examine the brain responses in 30 AN patients and 20 healthy women during the processing of negative words concerning interpersonal relationships. We investigated the relationship between alexithymia levels and brain activation in AN. AN patients showed significant activation of the orbitofrontal cortex, dorsolateral prefrontal cortex and medial prefrontal cortex while processing negative words concerning interpersonal relationships, as compared to the processing of neutral words. Moreover, the subjective rating of unpleasantness with negative words and neural activities in the amygdala, posterior cingulate cortex (PCC) and anterior cingulate cortex (ACC) negatively correlated with the level of alexithymia in AN. Our neuroimaging results suggest that AN patients tend to cognitively process negative words concerning interpersonal relationships, resulting in activation of the prefrontal cortex. Lower activation of the amygdala, PCC and ACC in response to these words may contribute to the impairments of emotional processing that are hallmarks of alexithymia. Functional abnormalities associated with alexithymia may be involved in the emotional processing impairments in AN patients.     

Emotion disrupts neural activity during selective attention in psychopathy

Dimensions of psychopathy are theorized to be associated with distinct cognitive and emotional abnormalities that may represent unique neurobiological risk factors for the disorder. This hypothesis was investigated by examining whether the psychopathic personality dimensions of fearless-dominance and impulsive-antisociality moderated neural activity and behavioral responses associated with selective attention and emotional processing during an emotion-word Stroop task in 49 adults. As predicted, the dimensions evidenced divergent selective-attention deficits and sensitivity to emotional distraction. Fearless-dominance was associated with disrupted attentional control to positive words, and activation in right superior frontal gyrus mediated the relationship between fearless-dominance and errors to positive words. In contrast, impulsive-antisociality evidenced increased behavioral interference to both positive and negative words and correlated positively with recruitment of regions associated with motivational salience (amygdala, orbitofrontal cortex, insula), emotion regulation (temporal cortex, superior frontal gyrus) and attentional control (dorsal anterior cingulate cortex). Individuals high on both dimensions had increased recruitment of regions related to attentional control (temporal cortex, rostral anterior cingulate cortex), response preparation (pre-/post-central gyri) and motivational value (orbitofrontal cortex) in response to negative words. These findings provide evidence that the psychopathy dimensions represent dual sets of risk factors characterized by divergent dysfunction in cognitive and affective processes.     

Characteristic prefrontal blood volume patterns when imaging body type,high-calorie food,and mother–child attachment in childhood anorexia nervosa: A near infrared spectroscopy study

The aim of this study was to investigate the prefrontal activation in childhood anorexia nervosa (AN) patients when imaging symptom-provocative factors such as body type, high-calorie food, and attachment between mother and child. The prefrontal activations during each task, in terms of blood volume changes, were measured by near infrared spectroscopy. Twelve females with childhood AN (mean age, 14.4 years old) and 13 age-matched healthy female controls (mean age, 14.3 years old) participated in this study. Both groups showed increased prefrontal blood volume when viewing images of each symptom-provocative factor. Unexpectedly, there was no significant difference in the prefrontal blood volume increases between the control group and the childhood AN group when viewing images of slender and obese body types and high-calorie food. On the other hand, images of mother–child attachment resulted in significantly greater increases in prefrontal blood volume in the childhood AN group than in the control group. These results indicated that prefrontal activation in AN might be associated with imaging attachment between mother and child, but not associated with imaging body type or high-calorie food.     

Grey matter volume in adolescents with anorexia nervosa and associated eating disorder symptoms

Anorexia nervosa (AN) is a mental health disorder of complex aetiology. Previous neuroimaging studies have found consistent global reductions in global grey matter volume of underweight girls with AN; however, differences in regional grey matter volumes are less consistent. The aims of this study were to investigate grey matter regional volumes of adolescent girls with AN before and after weight recovery and the relationship of any changes with clinical characteristics. We collected high‐resolution T1‐weighted images from 26 underweight girls with AN before weight gain and 20 healthy control volunteers. Clinical features were assessed using the Eating Disorder Examination Questionnaire. AN subjects displayed reduced grey matter volumes in the insula, amygdala, prefrontal, hippocampal and cingulate cortices and the precuneus, relative to healthy controls. In a subset of 10 AN subjects who were followed after weight recovery, grey matter volumes increased to near‐control levels in the orbito‐ and medial prefrontal, insular, left hippocampal and mid‐ and posterior cingulate cortices and precuneus. The recovery of the right anterior thalamus and the left orbitofrontal cortex was correlated with improvements in eating concerns and shape concerns, respectively. However, large parts of the anterior cingulate cortex, caudate nuclei and right hippocampus did not display any grey matter recovery following a short‐term of treatment. These results show that in adolescents with AN, some brain regions display marked recovery in grey matter volume following weight recovery, whereas others do not, considering grey mater recovery possibly linked to symptom improvement.     

Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers

Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.