Margaret M. Benningfield

Response of neural reward regions to food cues in autism spectrum disorders

BackgroundOne hypothesis for the social deficits that characterize autism spectrum disorders (ASD) is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards.MethodWe asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD) signal in response to the food imagesResultsWe found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD.ConclusionThese results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.

Co-occurring psychiatric symptoms are associated with increased psychological, social, and medical impairment in opioid dependent pregnant women

The interaction of psychiatric symptoms with drug dependence during pregnancy is not well understood. This study examines the relationship of psychiatric symptoms to severity of drug use and drug-related problems among participants in a clinical trial of pharmacologic treatment of opioid dependence during pregnancy (N = 174). A total of 64.6% reported additional psychiatric symptoms (48.6% mood symptoms, 40.0% anxiety symptoms, and 12.6% suicidal thinking). Women who endorsed co-occurring psychiatric symptoms showed more severe impairment on the Addiction Severity Index. Further investigation is warranted to understand the effect of psychiatric symptoms on long-term maternal and neonatal outcomes.

Brain Serotonin Function in MDMA (Ecstasy) Users: Evidence for Persisting Neurotoxicity

3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a popular recreational drug, and clinical trials are investigating MDMA as a treatment for anxiety. Animal models suggest that MDMA causes chronic serotonin neurotoxicity, especially in neocortex. Given the role of serotonin in a broad range of brain functions, it is critical to determine whether MDMA is associated with serotonin neurotoxicity in humans. Studies examining the presynaptic serotonin reuptake transporter (SERT) as a marker of serotonin axon integrity in MDMA users have generally found reductions in SERT binding (McCann et al, 2008; Urban et al, 2012; Kish et al, 2010). Although there is some evidence for SERT recovery in subcortical regions with prolonged abstinence (Buchert et al, 2006), there is little evidence suggesting SERT recovery in neocortex. In contrast to the SERT, the postsynaptic serotonin-2A receptor can serve as an indicator of presynaptic serotonin release if it upregulates in the face of reduced agonist signaling. We recently examined the status of neocortical serotonin-2A receptors in female MDMA users who had a median abstinence from MDMA of nearly 2 years. We predicted that MDMA-induced reductions in serotonin would lead to increased serotonin-2A receptors in MDMA users, and that lifetime MDMA use would be positively correlated with receptor level. Consistent with MDMA-induced chronic reductions in serotonin signaling, long-abstinent MDMA users had increased levels of serotonin-2A receptors in multiple cortical areas, and higher lifetime MDMA use predicted higher receptor levels (Figure 1) with no evidence for receptor normalization with long-term abstinence (Di Iorio et al, 2012). Urban et al 2012 also found increased serotonin-2A levels in MDMA users and they also measured SERT in the same cohort. SERT binding was lower in brain regions where the serotonin-2A receptors were elevated, a finding consistent with reduced serotonin and consequent upregulation of the serotonin-2A receptor. Figure 1 (a and b) Right-hemisphere and bilateral superior regions are depicted, respectively, in which lifetime ecstasy use correlates positively with serotonin-2A-binding potential in the ecstasy (MDMA) user group after adjusting for birth control, estrogen, ... If MDMA users actually have reduced serotonin signaling, there should be predictable effects of MDMA-induced reductions in serotonin on cortical neurophysiology. Serotonin is largely inhibitory in neocortex, therefore reductions in serotonin signaling should produce increased cortical excitability, reflected as increased activation with fMRI. In support of this hypothesis, we found that greater MDMA use was associated with greater occipital activation during visual stimulation in MDMA users, a finding consistent with increased cortical excitability and in line with the consequences of reduced serotonin signaling (Bauernfeind et al, 2011).

Amygdala-cingulate intrinsic connectivity is associated with degree of social inhibition.

The tendency to approach or avoid novel people is a fundamental human behavior and is a core dimension of social anxiety. Resting state fMRI was used to test for an association between social inhibition and intrinsic connectivity in 40 young adults ranging from low to high in social inhibition. Higher levels of social inhibition were associated with specific patterns of reduced amygdala-cingulate cortex connectivity. Connectivity was reduced between the superficial amygdala and the rostral cingulate cortex and between the centromedial amygdala and the dorsal anterior cingulate cortex. Social inhibition also modulated connectivity in several well-established intrinsic networks; higher social inhibition correlated with reduced connectivity with default mode and dorsal attention networks and enhanced connectivity in salience and executive control networks. These findings provide important preliminary evidence that social inhibition reflects differences in the underlying intrinsic connectivity of the brain in the absence of social stimuli or stressors.

Caudate responses to reward anticipation associated with delay discounting behavior in healthy youth

Highlights • Greater discounting of future rewards may be a marker for vulnerability for substance abuse.• We tested for an association between discounting and brain responses to reward in healthy youth.• Left ventromedial caudate activation during anticipation of potential reward was associated with the willingness to delay gratification.

Structural and functional bases of inhibited temperament

Children born with an inhibited temperament are at heightened risk for developing anxiety, depression and substance use. Inhibited temperament is believed to have a biological basis; however, little is known about the structural brain basis of this vulnerability trait. Structural MRI scans were obtained from 84 (44 inhibited, 40 uninhibited) young adults. Given previous findings of amygdala hyperactivity in inhibited individuals, groups were compared on three measures of amygdala structure. To identify novel substrates of inhibited temperament, a whole brain analysis was performed. Functional activation and connectivity were examined across both groups. Inhibited adults had larger amygdala and caudate volume and larger volume predicted greater activation to neutral faces. In addition, larger amygdala volume predicted greater connectivity with subcortical and higher order visual structures. Larger caudate volume predicted greater connectivity with the basal ganglia, and less connectivity with primary visual and auditory cortex. We propose that larger volume in these salience detection regions may result in increased activation and enhanced connectivity in response to social stimuli. Given the strong link between inhibited temperament and risk for psychiatric illness, novel therapeutics that target these brain regions and related neural circuits have the potential to reduce rates of illness in vulnerable individuals.

Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: preliminary results.

Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence.

Neurocircuitry underlying risk and resilience to social anxiety disorder

Almost half of children with an inhibited temperament will develop social anxiety disorder by late adolescence. Importantly, this means that half of children with an inhibited temperament will not develop social anxiety disorder. Studying adults with an inhibited temperament provides a unique opportunity to identify neural signatures of both risk and resilience to social anxiety disorder.

Being Present at School Implementing Mindfulness in Schools

Developmentally sensitive efforts to help students learn, practice, and regularly use mindfulness tactics easily and readily in and beyond the classroom are important to help them manage future stresses. Mindfulness emphasizes consciously focusing the mind in the present moment, purposefully, without judgment or attachment. Meditation extends this to setting aside time and places to practice mindfulness, and additionally, yoga includes physical postures and breathing techniques that enhance mindfulness and meditation. Several mindfulness programs and techniques have been applied in schools, with positive benefits reported. Some elements of these programs require modifications to be sensitive to the developmental state of the children receiving mindfulness training.

Sex differences in psychophysical and neurophysiological responses to pain in older adults: a cross-sectional study

BackgroundNeuroimaging studies in younger adults have demonstrated sex differences in brain processing of painful experimental stimuli. Such differences may contribute to findings that women suffer disproportionately from pain. It is not known whether sex-related differences in pain processing extend to older adults.MethodsThis cross-sectional study investigated sex differences in pain reports and brain response to pain in 12 cognitively healthy older female adults and 12 cognitively healthy age-matched older male adults (age range 65–81, median = 67). Participants underwent psychophysical assessments of thermal pain responses, functional MRI, and psychosocial assessment.ResultsWhen compared to older males, older females reported experiencing mild and moderate pain at lower stimulus intensities (i.e., exhibited greater pain sensitivity; Cohen’s d = 0.92 and 0.99, respectively, p < 0.01) yet did not report greater pain-associated unpleasantness. Imaging results indicated that, despite the lower stimulus intensities required to elicit mild pain detection in females, they exhibited less deactivations than males in regions associated with the default mode network (DMN) and in regions associated with pain affect (bilateral dorsolateral prefrontal cortex, somatomotor area, rostral anterior cingulate cortex (rACC), and dorsal ACC). Conversely, at moderate pain detection levels, males exhibited greater activation than females in several ipsilateral regions typically associated with pain sensation (e.g., primary (SI) and secondary somatosensory cortices (SII) and posterior insula). Sex differences were found in the association of brain activation in the left rACC with pain unpleasantness. In the combined sample of males and females, brain activation in the right secondary somatosensory cortex was associated with pain unpleasantness.ConclusionsCognitively healthy older adults in the sixth and seventh decades of life exhibit similar sex differences in pain sensitivity compared to those reported in younger individuals. However, older females did not find pain to be more unpleasant. Notably, increased sensitivity to mild pain in older females was reflected via less brain deactivation in regions associated with both the DMN and in pain affect. Current findings elevate the rACC as a key region associated with sex differences in reports of pain unpleasantness and brain deactivation in older adults. Also, pain affect may be encoded in SII in both older males and females.