Fever, abdominal pain, and lymphocytic ascites in a young immigrant from western Africa.

Tuberculous peritonitis is an uncommon disease in countries with low tuberculosis (TB) incidence, most often affecting non-white race, foreign-born individuals. We describe a case of TB with peritoneal involvement in a 32-year-old man immigrated to Italy from Burkina Faso, who presented with a history of fever, malaise, abdominal pain and abdominal swelling. Due to its nonspecific clinical presentation and paucibacillary nature, diagnosis of tuberculous peritonitis can be challenging, and requires a high index of suspicion. This report highlights the diagnostic challenges posed by tuberculous peritonitis and emphasizes the importance of imaging (computed tomography, CT) in identifying typical findings, and the value of histological examination of tissue specimens from peritoneum or any site of suspected TB as a tool for diagnosis confirmation.

Habenula-prefrontal resting-state connectivity in reactive aggressive men - A pilot study.

Disproportionate anger and reactive aggression in response to provocation are core symptoms of intermittent-explosive disorder (IED). Previous research shows a link between the propensity for aggression in healthy individuals and altered functioning of prefrontal-limbic and default-mode networks (DMN) at rest when no provocation is present. In a pilot study, we used resting-state functional magnetic resonance imaging to investigate the effects of pronounced reactive aggression in men, exemplified by IED, on the functional organization of resting-state brain networks including subcortical nodes such as the habenula previously implicated in aggression in preclinical models. Graph theory was applied to resting-state networks to determine alterations in global efficiency and clustering in high reactive aggressive men compared to low reactive aggressive men (controls). Further, we computed within-group correlations between trait aggression and graph measures, as well as within-group whole-brain seed-to-voxel regression analyses between trait aggression and habenula resting-state functional connectivity (rsFC). Reactive aggressive men compared to controls showed higher global efficiency in the left habenula, the left pulvinar in the thalamus, the left dorso-lateral prefrontal cortex, and the right temporal pole, as well as a trend for decreased clustering in DMN nodes. In the reactive aggressive group, high levels of trait aggression were linked to lower global efficiency of the left habenula, and to lower rsFC between the left habenula and the left ventro-lateral prefrontal cortex, a core region involved in inhibitory control. Together with preclinical evidence, our findings in men underline the relevance of aberrant habenula-prefrontal connectivity for the severity of aggressive behavior. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

Association of genetic ancestry with striatal dopamine D2/D3 receptor availability.

Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between genetic ancestry and striatal D2R. Here, we show that ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [11C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes). Effects of ethnicity on D2R were not driven by variation in dopaminergic candidate genes. Instead, candidate gene associations with striatal D2R were diminished when correcting for ancestry. These findings imply that future studies investigating D2 receptor genes should covary for genetic ancestry or study homogeneous populations. Moreover, ancestry studies on human neurobiology should control for socioeconomic differences between ethnic groups.

Alcohol affects brain functional connectivity and its coupling with behavior: greater effects in male heavy drinkers.

Acute and chronic alcohol exposure significantly affect behavior but the underlying neurobiological mechanisms are still poorly understood. Here, we used functional connectivity density (FCD) mapping to study alcohol-related changes in resting brain activity and their association with behavior. Heavy drinkers (HD, N=16, 16 males) and normal controls (NM, N=24, 14 males) were tested after placebo and after acute alcohol administration. Group comparisons showed that NM had higher FCD in visual and prefrontal cortices, default mode network regions and thalamus, while HD had higher FCD in cerebellum. Acute alcohol significantly increased FCD within the thalamus, impaired cognitive and motor functions, and affected self-reports of mood/drug effects in both groups. Partial least squares regression showed that alcohol-induced changes in mood/drug effects were associated with changes in thalamic FCD in both groups. Disruptions in motor function were associated with increases in cerebellar FCD in NM and thalamus FCD in HD. Alcohol-induced declines in cognitive performance were associated with connectivity increases in visual cortex and thalamus in NM, but in HD, increases in precuneus FCD were associated with improved cognitive performance. Acute alcohol reduced 'neurocognitive coupling', the association between behavioral performance and FCD (indexing brain activity), an effect that was accentuated in HD compared with NM. Findings suggest that reduced cortical connectivity in HD contribute to decline in cognitive abilities associated with heavy alcohol consumption, whereas increased cerebellar connectivity in HD may have compensatory effects on behavioral performance. The results reveal how drinking history alters the association between brain FCD and individual differences in behavioral performance.

Association between striatal dopamine D2/D3 receptors and brain activation during visual attention: effects of sleep deprivation.

Sleep deprivation (SD) disrupts dopamine (DA) signaling and impairs attention. However, the interpretation of these concomitant effects requires a better understanding of dopamine's role in attention processing. Here we test the hypotheses that D2/D3 receptors (D2/D3R) in dorsal and ventral striatum would distinctly regulate the activation of attention regions and that, by decreasing D2/D3, SD would disrupt these associations. We measured striatal D2/D3R using positron emission tomography with [(11)C]raclopride and brain activation to a visual attention (VA) task using 4-Tesla functional magnetic resonance imaging. Fourteen healthy men were studied during rested wakefulness and also during SD. Increased D2/D3R in striatum (caudate, putamen and ventral striatum) were linearly associated with higher thalamic activation. Subjects with higher D2/D3R in caudate relative to ventral striatum had higher activation in superior parietal cortex and ventral precuneus, and those with higher D2/D3R in putamen relative to ventral striatum had higher activation in anterior cingulate. SD impaired the association between striatal D2/D3R and VA-induced thalamic activation, which is essential for alertness. Findings suggest a robust DAergic modulation of cortical activation during the VA task, such that D2/D3R in dorsal striatum counterbalanced the stimulatory influence of D2/D3R in ventral striatum, which was not significantly disrupted by SD. In contrast, SD disrupted thalamic activation, which did not show counterbalanced DAergic modulation but a positive association with D2/D3R in both dorsal and ventral striatum. The counterbalanced dorsal versus ventral striatal DAergic modulation of VA activation mirrors similar findings during sensorimotor processing (Tomasi et al., 2015) suggesting a bidirectional influence in signaling between the dorsal caudate and putamen and the ventral striatum.

Recovery of brain structural abnormalities in morbidly obese patients after bariatric surgery.

BACKGROUND/OBJECTIVES: Obesity-related brain structural abnormalities have been reported extensively, and bariatric surgery (BS) is currently the most effective intervention to produce sustained weight reduction in overtly obese (OB) people. It is unknown whether BS can repair the brain circuitry abnormalities concomitantly with long-term weight loss. SUBJECTS/METHODS: In order to investigate whether BS promotes neuroplastic structural recovery in morbidly OB patients, we quantified fractional anisotropy (FA), mean diffusivity (MD) and gray (GM) and white (WM) matter densities in 15 morbidly OB patients and in 18 normal weight (NW) individuals. OB patients were studied at baseline and also 1 month after laparoscopic sleeve gastrectomy surgery. RESULTS: Two-sample t-test between OB (baseline) and NW groups showed decreased FA values, GM/WM densities and increased MD value in brain regions associated with food intake control (that is, caudate, orbitofrontal cortex, body and genu of corpus callosum) and cognitive-emotion regulation (that is, inferior frontal gyrus, hippocampus, insula, external capsule) (P<0.05, family-wise error correction). Paired t-test in the OB group between before and after surgery showed that BS generated partial neuroplastic structural recovery in the OB group, but the differences had relative less strength and smaller volume (P<0.001). CONCLUSIONS: This study provides the first anatomical evidence for BS-induced acute neuroplastic recovery that might in part mediate the long-term benefit of BS in weight reduction. It also highlights the importance of this line of gut-brain axis research employing the combined BS and neuroimaging model for identifying longitudinal changes in brain structure that correlated with obesity status.

Temporal Changes in Local Functional Connectivity Density Reflect the Temporal Variability of the Amplitude of Low Frequency Fluctuations in Gray Matter.

Data-driven functional connectivity density (FCD) mapping is being increasingly utilized to assess brain connectomics at rest in the healthy brain and its disruption in neuropsychiatric diseases with the underlying assumption that the spatiotemporal hub distribution is stationary. However, recent studies show that functional connectivity is highly dynamic. Here we study the temporal variability of the local FCD (lFCD) at high spatiotemporal resolution (2-mm isotropic; 0.72s) using a sliding-window approach and 'resting-state' datasets from 40 healthy subjects collected under the Human Connectome Project. Prominent functional connectivity hubs in visual and posterior parietal cortices had pronounced temporal changes in local FCD. These dynamic patterns in the strength of the lFCD hubs occurred in cortical gray matter with high sensitivity (up to 85%) and specificity (> 85%) and showed high reproducibility (up to 72%) across sessions and high test-retest reliability (ICC(3,1) > 0.5). The temporal changes in lFCD predominantly occurred in medial occipitoparietal regions and were proportional to the strength of the connectivity hubs. The temporal variability of the lFCD was associated with the amplitude of the low frequency fluctuations (ALFF). Pure randomness did not account for the probability distribution of lFCD. Shannon entropy increased in proportion to the strength of the lFCD hubs suggesting high average flow of information per unit of time in the lFCD hubs, particularly in medial occipitoparietal regions. Thus, the higher dynamic range of the lFCD hubs is consistent with their role in the complex orchestration of interacting brain networks.

Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers.

Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [(11)C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes.

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

The (87)Sr/(86)Sr strontium isotopic systematics applied to Glera vineyards: a tracer for the geographical origin of the Prosecco.

Glera vineyards from the Prosecco wine district in northern Italy have been characterised in terms of the (87)Sr/(86)Sr isotope-ratio of musts from the 2010, 2011 and 2012 vintages, coupled with the isotopic analysis of Sr in the labile fraction of the soils of provenance. For a single vineyard, detailed Sr isotopic analyses were carried out in sequentially extracted soil fractions at three different depths, and in the grape components (skin, seeds, must and stem), in order to verify the lack of Sr isotopic fractionation within the plant. The (87)Sr/(86)Sr in must, seeds and stem overlaps within experimental uncertainties; skins are shifted towards a lower Sr isotopic composition. A large range of Sr isotopic compositions ((87)Sr/(86)Sr between 0.70706 and 0.71215) characterizes musts from the different vineyards, notwithstanding the relatively limited extension of the investigated geographic area. A statistically significant correspondence between the soil labile fraction and must is observed.

Stimulant-induced dopamine increases are markedly blunted in active cocaine abusers.

Dopamine signaling in nucleus accumbens is essential for cocaine reward. Interestingly, imaging studies have reported blunted dopamine increases in striatum (assessed as reduced binding of [(11)C]raclopride to D2/D3 receptors) in detoxified cocaine abusers. Here, we evaluate whether the blunted dopamine response reflected the effects of detoxification and the lack of cocaine-cues during stimulant exposure. For this purpose we studied 62 participants (43 non-detoxified cocaine abusers and 19 controls) using positron emission tomography and [(11)C]raclopride (radioligand sensitive to endogenous dopamine) to measure dopamine increases induced by intravenous methylphenidate and in 24 of the cocaine abusers, we also compared dopamine increases when methylphenidate was administered concomitantly with a cocaine cue-video versus a neutral-video. In controls, methylphenidate increased dopamine in dorsal (effect size 1.4; P<0.001) and ventral striatum (location of accumbens) (effect size 0.89; P<0.001), but in cocaine abusers methylphenidate's effects did not differ from placebo and were similar whether cocaine-cues were present or not. In cocaine abusers despite the markedly attenuated dopaminergic effects, the methylphenidate-induced changes in ventral striatum were associated with intense drug craving. Our findings are consistent with markedly reduced signaling through D2 receptors during intoxication in active cocaine abusers regardless of cues exposure, which might contribute to compulsive drug use.

Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues.

OBJECTIVE: The significant weight loss observed with combination naltrexone-sustained release (SR) 32 mg and bupropion SR 360 mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment. METHODS: Forty women (31.1±8.1 years; body mass index: 32.5±3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (>100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation (∼14 h) were assessed before and after treatment. RESULTS: The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues (P<0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P<0.05). CONCLUSIONS: Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity.

Obesity and addiction: neurobiological overlaps.

Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction.

Dopaminergic involvement during mental fatigue in health and cocaine addiction.

Dopamine modulates executive function, including sustaining cognitive control during mental fatigue. Using event-related functional magnetic resonance imaging (fMRI) during the color-word Stroop task, we aimed to model mental fatigue with repeated task exposures in 33 cocaine abusers and 20 healthy controls. During such mental fatigue (indicated by increased errors, and decreased post-error slowing and dorsal anterior cingulate response to error as a function of time-on-task), healthy individuals showed increased activity in the dopaminergic midbrain to error. Cocaine abusers, characterized by disrupted dopamine neurotransmission, showed an opposite pattern of response. This midbrain fMRI activity with repetition was further correlated with objective indices of endogenous motivation in all subjects: a state measure (task reaction time) and a trait measure (dopamine D2 receptor availability in caudate, as revealed by positron emission tomography data collected in a subset of this sample, which directly points to a contribution of dopamine to these results). In a second sample of 14 cocaine abusers and 15 controls, administration of an indirect dopamine agonist, methylphenidate, reversed these midbrain responses in both groups, possibly indicating normalization of response in cocaine abusers because of restoration of dopamine signaling but degradation of response in healthy controls owing to excessive dopamine signaling. Together, these multimodal imaging findings suggest a novel involvement of the dopaminergic midbrain in sustaining motivation during fatigue. This region might provide a useful target for strengthening self-control and/or endogenous motivation in addiction.

Effects of irrigation on the seasonal abundance of Empoasca vitis in north-Italian vineyards.

The effect of irrigation on the abundance of Empoasca vitis (Göthe) populations was investigated in four vineyards located in northeastern Italy. In two experiments, we compared leafhopper population densities in plots irrigated (micro-spray irrigation system) or nonirrigated. In another experiment, we studied the effect of various irrigation systems on E. vitis populations over two successive seasons. In particular, five treatments were compared: control (not irrigated), traditional drip system, three types of subirrigation varying in distance from the row (40, 135, and 95 cm). In this vineyard, stem water potential was monitored with a pressure chamber. E. vitis population densities were affected by irrigation, with higher densities of this pest recorded on irrigated vines. Highest E. vitis densities were detected in drip irrigation plots compared with nonirrigated plots where water stress was highest. Moderate water stress (subirrigation plots) was associated with intermediate leafhopper densities. Implications for integrated pest management are discussed.

Resting functional connectivity of language networks: characterization and reproducibility.

The neural basis of language comprehension and production has been associated with superior temporal (Wernicke's) and inferior frontal (Broca's) cortical areas, respectively. However, recent resting-state functional connectivity (RSFC) and lesion studies have implicated a more extended network in language processing. Using a large RSFC data set from 970 healthy subjects and seed regions in Broca's and Wernicke's, we recapitulate this extended network that includes not only adjoining prefrontal, temporal and parietal regions but also bilateral caudate and left putamen/globus pallidus and subthalamic nucleus. We also show that the language network has predominance of short-range functional connectivity (except posterior Wernicke's area that exhibited predominant long-range connectivity), which is consistent with reliance on local processing. Predominantly, long-range connectivity was left lateralized (except anterior Wernicke's area that exhibited rightward lateralization). The language network also exhibited anti-correlated activity with auditory (only for Wernicke's area) and visual cortices that suggests integrated sequential activity with regions involved with listening or reading words. Assessment of the intra-subject's reproducibility of this network and its characterization in individuals with language dysfunction is required to determine its potential as a biomarker for language disorders.

Aging and functional brain networks.

Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associated with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.

Decreased dopamine activity predicts relapse in methamphetamine abusers.

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [(11)C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.