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Background: Dysregulated ventral striatum function has been proposed as one important process occurring in individuals with substance use disorder. This study investigates the role of altered reward and loss anticipation, which is an important component of impaired decision-making, impulsivity, and vulnerability to relapse in individuals with amphetamine use disorder (AMP). Aims: To determine whether AMP is associated with blunted striatum, prefrontal cortex, and insula signals during win and loss anticipation. Methods: Participants with and without AMP (AMP+ n = 46, AMP− n = 90) from the Tulsa 1000 study completed a monetary incentive delay (MID) task during functional magnetic resonance imaging. Results: Group main effects indicated that: (1) AMP+ exhibited lower bilateral caudate/putamen and left nucleus accumbens signal than AMP− across anticipation of wins and losses; and (2) AMP+ showed slower reaction times than AMP− during loss anticipation. Group*condition interactions demonstrated that AMP+ exhibited greater right amygdala signal than AMP− while anticipating large wins, a pattern that reversed when anticipating small losses. Left caudate/putamen attenuations in AMP+ during small loss anticipation were also evident. Groups did not differ in prefrontal or insula signals. Conclusions: AMP+ individuals have altered neural processing and response patterns during reward and loss anticipation, potentially reflecting impairments in dopamine function, which may influence their decision-making and reactions to different win/loss scenarios. These findings help to explain why AMP+ have difficulty with decision-making and exhibit a heightened focus on immediate rewards or punishments. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to test whether there are sex differences in the relationship between impulsivity and amphetamine use disorder (AMP). Design: A naturalistic cross‐sectional design was used. Setting: The Tulsa 1000 study was held in Tulsa, OK, USA. Participants: There were two groups in this study: AMP+ (29F, 20M) and AMP– (57F, 33M). Measurements This project focuses on data related to impulsivity: UPPS‐P impulsive behavior scale and a stop signal task (SST) during functional magnetic resonance imaging (fMRI) recording. Group, sex and their interaction were compared for UPPS‐P ratings and SST fMRI and behavioral responses. Findings AMP+ reported higher UPPS‐P positive and negative urgency scores (Ps < 0.001; r = 0.56 and 0.51) and displayed greater bilateral insula and amygdala responses across correct SST trials (Ps < 0.001, g range = 0.57–0.81) than AMP–. fMRI results indicated that AMP+ exhibited larger right anterior/middle insula, amygdala and nucleus accumbens signals during successful difficult stop trials than AMP– (Ps < 0.01; g = 0.63, 0.54 and 0.44, respectively). Crucially, two group × sex effects emerged: (a) within females, AMP+ reported larger UPPS‐P lack of premeditation scores than AMP– (P < 0.001, r = 0.51), and (b) within males, AMP+ showed greater left middle insula signals than AMP– across correct SST trials (P = 0.01, g = 0.78). Conclusions: Both female and male amphetamine users appear to be characterized by rash action in the presence of positive and negative mood states as well as heightened recruitment of right hemisphere regions during behavioral inhibition. In contrast, planning ahead may be particularly difficult for female amphetamine users, whereas male amphetamine users may need to recruit additional left hemisphere resources during inhibitory processing. [ABSTRACT FROM AUTHOR]

The parent-child relationship and family context influence the development of emotion regulation (ER) brain circuitry and related skills in children and adolescents. Although both parents' and children's ER neurocircuitry simultaneously affect how they interact with one another, neuroimaging studies of parent-child relationships typically include only one member of the dyad in brain imaging procedures. The current study examined brain activation related to parenting and ER in parent-adolescent dyads during concurrent fMRI scanning with a novel task – the Testing Emotional Attunement and Mutuality (TEAM) task. The TEAM task includes feedback trials indicating the other dyad member made an error, resulting in a monetary loss for both participants. Results indicate that positive parenting practices as reported by the adolescent were positively correlated with parents' hemodynamic activation of the ventromedial prefrontal cortex, a region related to empathy, during these error trials. Additionally, during feedback conditions both parents and adolescents exhibited fMRI activation in ER-related regions, including the dorsolateral prefrontal cortex, anterior insula, fusiform gyrus, thalamus, caudate, precuneus, and superior parietal lobule. Adolescents had higher left amygdala activation than parents during the feedback condition. These findings demonstrate the utility of dyadic fMRI scanning for investigating relational processes, particularly in the parent-child relationship. [ABSTRACT FROM AUTHOR]

The homeostatic regulation of feeding behavior requires an organism to be able to integrate information from its internal environment, including peripheral visceral signals about the body's current energy needs, with information from its external environment, such as the palatability of energy-rich food stimuli. The insula, which serves as the brain's primary sensory cortex for representing both visceral signals from the body and taste signals from the mouth and tongue, is a likely candidate region in which this integration might occur. However, to date it has been unclear whether information from these two homeostatically critical faculties is merely co-represented in the human insula, or actually integrated there. Recent functional neuroimaging evidence of a common substrate for visceral interoception and taste perception within the human dorsal mid-insula suggests a model whereby a single population of neurons may integrate viscerosensory and gustatory signals. To test this model, we used fMRI-Adaptation to identify whether insula regions that exhibit repetition suppression following repeated interoception trials would then also exhibit adapted responses to subsequent gustatory stimuli. Multiple mid and anterior regions of the insula exhibited adaptation to interoceptive trials specifically, but only the dorsal mid-insula regions exhibited an adapted gustatory response following interoception. The discovery of this gustatory-interoceptive convergence within the neurons of the human insula supports the existence of a heretofore-undocumented neural pathway by which visceral signals from the periphery modulate the activity of brain regions involved in feeding behavior. Hum Brain Mapp 38:2150-2164, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective: Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites.Method: Using functional MRI, brain activity was compared in unmedicated depressed patients with increased or decreased appetite and healthy control subjects while viewing photographs of food and nonfood objects. The authors also measured how resting-state functional connectivity related to subjects' food pleasantness ratings.Results: Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings.Conclusions: Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body's physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes. [ABSTRACT FROM AUTHOR]

Unmedicated individuals with major depressive disorder (MDD) show abnormal interoception, but it is unclear whether antidepressant treatment via serotonergic medication alters this relationship. The current cross-sectional study examined associations between neural and behavioral indices of interoceptive processing and chronic serotonergic medication administration in MDD. 47 selective serotonin reuptake inhibitor (SSRI)-medicated MDD (MDD-SSRI) individuals were propensity-matched with 48 unmedicated current MDD (MDD-UnMed) and 41 healthy comparison (HC) participants on demographics including age, sex, body mass index, education, as well as on dimensional scales of symptom severity including depression and anxiety. All participants completed an interoceptive attention task during functional magnetic resonance imaging, and a behavioral heartbeat tapping task under three conditions: Guessing, No Guessing, and Breath Hold. Relative to HC, both MDD groups: (1) exhibited lower mid-insula, amygdala, putamen, and caudate activation during interoceptive versus exteroceptive attention; and (2) showed poorer heartbeat tapping performance during the Breath Hold condition. However, the MDD-SSRI group reported higher intensity ratings of heartbeat and stomach sensations than MDD-UnMed and HC during the interoceptive attention task. These findings suggest that the attenuated patterns of neural activation observed in depressed individuals during interoceptive attention are not ameliorated by the chronic administration of serotonergic medications. However, amplified interoceptive sensation ratings suggest a potential impact of chronic serotonergic medication on conscious experiences of internal body states. Future investigations will need to determine the extent to which serotonergic medications acutely influence interoceptive processing, and whether such changes play a role in therapeutic responses during treatment initiation. • MDD patients exhibited lower self-reported interoceptive awareness than HC. • MDD patients showed lower insula, amygdala, and striatum activation than HC. • Insula activation did not differ between unmedicated and SSRI-medicated MDD. • MDD-SSRI displayed greater interoceptive sensation ratings than MDD-UnMed and HC. [ABSTRACT FROM AUTHOR]

The classic estrogen 17ß-estradiol (E2) was recently identified as a novel modulator of hearing function. It is produced rapidly, in an experience-dependent fashion, by auditory cortical neurons of both males and females. This brain-generated E2 enhances the efficiency of auditory coding and improves the neural and behavioral discrimination of auditory cues. Remarkably, the effects of E2 are long-lasting and persist for hours after local rises in hormone levels have subsided. The mechanisms and functional consequences of this E2-induced plasticity of auditory responses are unknown. Here, we addressed these issues in the zebra finch model by combining intracerebral pharmacology, biochemical assays, in vivo neurophysiology in awake animals, and computational and information theoretical approaches. We show that auditory experience activates the MAPK pathway in an E2-dependent manner. This effect is mediated by estrogen receptor β (ERß), which directly associates with MEKK1 to sequentially modulate MEK and ERK activation, where the latter is required for the engagement of downstream molecular targets. We further show that E2-mediated activation of the MAPK cascade is required for the long-lasting enhancement of auditory-evoked responses in the awake brain. Moreover, a functional consequence of this E2/MAPK activation is to sustain enhanced information handling and neural discrimination by auditory neurons for several hours following hormonal challenge. Our results demonstrate that brain-generated E2 engages, via a nongenomic interaction between an estrogen receptor and a kinase, a persistent form of experience-dependent plasticity that enhances the neural coding and discrimination of behaviorally relevant sensory signals in the adult vertebrate brain. [ABSTRACT FROM AUTHOR]

The classic female estrogen, 17β-estradiol (E2), has been repeatedly shown to affect the perceptual processing of visual cues. Although gonadal E2 has often been thought to influence these processes, the possibility that central visual processing may be modulated by brain-generated hormone has not been explored. Here we show that estrogen-associated circuits are highly prevalent in the mouse primary visual cortex (V1). Specifically, we cloned aromatase, a marker for estrogen-producing neurons, and the classic estrogen receptors (ERs) ERα and ERβ, as markers for estrogen-responsive neurons, and conducted a detailed expression analysis via in-situ hybridization. We found that both monocular and binocular V1 are highly enriched in aromatase- and ER-positive neurons, indicating that V1 is a site of production and sensitivity to estrogens. Using double-fluorescence in-situ hybridization, we reveal the neurochemical identity of estrogenproducing and -sensitive cells in V1, and demonstrate that they constitute a heterogeneous neuronal population. We further show that visual experience engages a large population of aromatase-positive neurons and, to a lesser extent, ERexpressing neurons, suggesting that E2 levels may be locally regulated by visual input in V1. Interestingly, acute episodes of visual experience do not affect the density or distribution of estrogen-associated circuits. Finally, we show that adult mice dark-reared from birth also exhibit normal distribution of aromatase and ERs throughout V1, suggesting that the implementation and maintenance of estrogen-associated circuits is independent of visual experience. Our findings demonstrate that the adult V1 is a site of production and sensitivity to estrogens, and suggest that locally-produced E2 may shape visual cortical processing. [ABSTRACT FROM AUTHOR]

Sex steroid hormones influence the perceptual processing of sensory signals in vertebrates. In particular, decades of research have shown that circulating levels of estrogen correlate with hearing function. The mechanisms and sites of action supporting this sensory-neuroendocrine modulation, however, remain unknown. Here we combined a molecular cloning strategy, fluorescence in-situ hybridization and unbiased quantification methods to show that estrogen-producing and -sensitive neurons heavily populate the adult mouse primary auditory cortex (AI). We also show that auditory experience in freely-behaving animals engages estrogen-producing and -sensitive neurons in AI. These estrogen-associated networks are greatly stable, and do not quantitatively change as a result of acute episodes of sensory experience. We further demonstrate the neurochemical identity of estrogen-producing and estrogen-sensitive neurons in AI and show that these cell populations are phenotypically distinct. Our findings provide the first direct demonstration that estrogen-associated circuits are highly prevalent and engaged by sensory experience in the mouse auditory cortex, and suggest that previous correlations between estrogen levels and hearing function may be related to brain-generated hormone production. Finally, our findings suggest that estrogenic modulation may be a central component of the operational framework of central auditory networks. [ABSTRACT FROM AUTHOR]

(1) Background: Growing evidence indicates that inflammation can induce neural circuit dysfunction and plays a vital role in the pathogenesis of major depressive disorder (MDD). Nevertheless, whether inflammation affects the integrity of white matter pathways is only beginning to be explored. (2) Methods: We computed quantitative anisotropy (QA) from diffusion magnetic resonance imaging as an index of white matter integrity and regressed QA on C-reactive protein (CRP), controlling for age, sex, and BMI, in 176 participants with MDD. (3) Results: The QA values of several white matter tracts were negatively correlated with CRP concentration (standardized beta coefficient = −0.22, 95%CI = −0.38–−0.06, FDR < 0.05). These tracts included the bilateral cortico-striatal tracts, thalamic radiations, inferior longitudinal fasciculi, corpus callosum (the forceps minor portion and the tapetum portion), cingulum bundles, and the left superior longitudinal fasciculus III. Importantly, the association remained robust after regressing up to twelve potential confounders. The bilateral fornix and a small portion of the thalamic radiation showed a positive association with CRP levels, but these associations did not remain significant after adjusting for confounders. (4) Conclusions: Peripheral inflammation may contribute to the etiology of MDD by impacting the microstructural integrity of brain corticolimbic white matter pathways. [ABSTRACT FROM AUTHOR]

• We tested neural associations of dyadic mental health symptoms in error processing. • Parent depression positively associated with parent dorsolateral PFC activity. • Parent anxiety positively associated with adolescent anterior insula activity. • Adolescent depression/anxiety negatively associated with parent default mode activity. • In sum, results suggest mental health symptoms may have dyadic neural effects. How parents manifest symptoms of anxiety or depression may affect how children learn to modulate their own distress, thereby influencing the children's risk for developing an anxiety or mood disorder. Conversely, children's mental health symptoms may impact parents' experiences of negative emotions. Therefore, mental health symptoms can have bidirectional effects in parent-child relationships, particularly during moments of distress or frustration (e.g., when a parent or child makes a costly mistake). The present study used simultaneous functional magnetic resonance imaging (fMRI) of parent-adolescent dyads to examine how brain activity when responding to each other's costly errors (i.e., dyadic error processing) may be associated with symptoms of anxiety and depression. While undergoing simultaneous fMRI scans, healthy dyads completed a task involving feigned errors that indicated their family member made a costly mistake. Inter-brain, random-effects multivariate modeling revealed that parents who exhibited decreased medial prefrontal cortex and posterior cingulate cortex activation when viewing their child's costly error response had children with more symptoms of depression and anxiety. Adolescents with increased anterior insula activation when viewing a costly error made by their parent had more anxious parents. These results reveal cross-brain associations between mental health symptomatology and brain activity during parent-child dyadic error processing. [ABSTRACT FROM AUTHOR]