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The central gustatory pathway encompasses multiple subcortical and cortical regions whose neural functional connectivity can be modulated by taste stimulation. While gustatory perception has been previously linked to sex, whether and how the gustatory network differently responds to basic tastes between men and women is unclear. Here, we defined the regions of the central gustatory network by a meta-analysis of 35 fMRI taste activation studies and then analyzed the taste-evoked functional connectivity between these regions in 44 subjects (19 women) in a separate 3 Tesla activation study where sweet and bitter solutions, at five concentrations each, were administered during scanning. From the meta-analysis, a network model was set up, including bilateral anterior, middle and inferior insula, thalamus, precentral gyrus, left amygdala, caudate and dorsolateral prefrontal cortex. Higher functional connectivity than in women was observed in men between the right middle insula and bilateral thalami for bitter taste. Men exhibited higher connectivity than women at low bitter concentrations and middle-high sweet concentrations between bilateral thalamus and insula. A graph-based analysis expressed similar results in terms of nodal characteristics of strength and centrality. Our findings add new insights into the mechanisms of taste processing by highlighting sex differences in the functional connectivity of the gustatory network as modulated by the perception of sweet and bitter tastes. These results shed more light on the neural origin of sex-related differences in gustatory perception and may guide future research on the pathophysiology of taste perception in humans.

Deficit schizophrenia is a subtype of schizophrenia presenting primary and enduring negative symptoms (NS). Although one of the most updated hypotheses indicates a relationship between NS and impaired motivation, only a few studies have investigated abnormalities of motivational circuits in subjects with deficit schizophrenia (DS). Our aim was to investigate structural connectivity within motivational circuits in DS. We analyzed diffusion tensor imaging (DTI) data from 46 subjects with schizophrenia (SCZ) and 35 healthy controls (HCs). SCZ were classified as DS (n = 9) and non-deficit (NDS) (n = 37) using the Schedule for Deficit Syndrome. The connectivity index (CI) and the Fractional Anisotropy (FA) of the connections between selected brain areas involved in motivational circuits were examined. DS, as compared with NDS and HCs, showed increased CI between the right amygdala and dorsal anterior insular cortex and increased FA of the pathway connecting the left nucleus accumbens with the posterior insular cortex. Our results support previous evidence of distinct neurobiological alterations underlying different clinical subtypes of schizophrenia. DS, as compared with NDS and HCs, may present an altered pruning process (consistent with the hyperconnectivity) in cerebral regions involved in updating the stimulus value to guide goal-directed behavior.

Background Here, we evaluate the effects of a diet rich in low-glycaemic index carbohydrates and fibre (CHO/Fibre diet) or monounsaturated fatty acids (MUFA diet), on fasting and postprandial adiponectin concentrations and their relationship with the beneficial effects of the experimental diets on postprandial glucose metabolism and liver fat in type 2 diabetes (T2D).Methods Fasting and postprandial adiponectin plasma concentrations were measured before and after dietary interventions in the participants to a randomized controlled trial (NCT01025856), wherein 37 men and 8 women with T2D, aged 35-70 years, followed a CHO/Fibre diet or a MUFA diet for an 8-week period. Hepatic fat content by H-1 NMR and fasting and postprandial plasma glucose and insulin measurements were also available.Results Fasting adiponectin plasma levels did not change after both diets. Postprandial adiponectin significantly increased after the CHO/fibre diet (9.9 +/- 1.6 mu g/mL vs. 10.8 +/- 2.3 mu g/mL; P = .033) but not after the MUFA diet (10.6 +/- 1.8 mu g/mL vs. 10.6 +/- 1.6 mu g/mL; P = .935) with a significant difference between changes (P = .035). In the combined CHO/Fibre and MUFA groups, fasting and postprandial adiponectin significantly and inversely correlated with postprandial insulin iAUC at baseline and after intervention, and with liver fat content after intervention.Conclusions A diet rich in CHO/Fibre increased postprandial plasma adiponectin significantly more than a MUFA diet in patients with T2D. Independently of diet, adiponectin levels associated with postprandial insulin concentrations. The dietary interventions modulated the relationship between adiponectin and liver fat.

Both normal gray matter atrophy and brain tissue relaxation rates, in addition to total lesion volume, have shown significant correlations with cognitive test scores in multiple sclerosis (MS). Aim of the study was to assess the relative contributions of macro- and microstructural changes of both normal and abnormal brain tissues, probed, respectively, by their volumes and relaxation rates, to the cognitive status and physical disability of MS patients. MRI studies from 241 patients with relapsing–remitting MS were retrospectively analyzed by fully automated multiparametric relaxometric segmentation. Ordinal backward regression analysis was applied to the resulting volumes and relaxation rates of both normal (gray matter, normal-appearing white matter and CSF) and abnormal (T2-weighted lesions) brain tissues, controlling for age, sex and disease duration, to identify the main independent contributors to the cognitive status, as measured by the percentage of failed tests at a cognitive test battery (Rao’s Brief Repeatable Battery and Stroop test, available in 186 patients), and to the physical disability, as assessed by the Expanded Disability Status Scale (EDSS). The R1 relaxation rate (a putative marker of tissue disruption) of the MS lesions appeared the single most significant contributor to cognitive impairment (p

Background Overconsumption of dietary sugars, fructose in particular, is linked to cardiovascular risk factors such as type 2 diabetes, obesity, dyslipidemia and nonalcoholic fatty liver disease. However, clinical studies have to date not clarified whether these adverse cardiometabolic effects are induced directly by dietary sugars, or whether they are secondary to weight gain. Objectives To assess the effects of fructose (75 g day−1), served with their habitual diet over 12 weeks, on liver fat content and other cardiometabolic risk factors in a large cohort (n = 71) of abdominally obese men. Methods We analysed changes in body composition, dietary intake, an extensive panel of cardiometabolic risk markers, hepatic de novo lipogenesis (DNL), liver fat content and postprandial lipid responses after a standardized oral fat tolerance test (OFTT). Results Fructose consumption had modest adverse effects on cardiometabolic risk factors. However, fructose consumption significantly increased liver fat content and hepatic DNL and decreased β-hydroxybutyrate (a measure of β-oxidation). The individual changes in liver fat were highly variable in subjects matched for the same level of weight change. The increase in liver fat content was significantly more pronounced than the weight gain. The increase in DNL correlated positively with triglyceride area under the curve responses after an OFTT. Conclusion Our data demonstrated adverse effects of moderate fructose consumption for 12 weeks on multiple cardiometabolic risk factors in particular on liver fat content despite only relative low increases in weight and waist circumference. Our study also indicates that there are remarkable individual differences in susceptibility to visceral adiposity/liver fat after real-world daily consumption of fructose-sweetened beverages over 12 weeks.

Background and aims: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. Methods and results: As many as 66 obese (BMI 26-40 kg/m(2)) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). Conclusion: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Eating disorders (EDs) have a possible neurodevelopmental pathogenesis. Our study aim was to assess regional cortical thickness (CT), local gyrification index (lGI) and fractal dimensionality (FD), as specific markers of cortical neurodevelopment in ED females. Twenty-two women with acute anorexia nervosa (acuAN), 10 with recovered anorexia nervosa (recAN), 24 with bulimia nervosa (BN) and 35 female healthy controls (HC) underwent a 3T MRI scan. All data were processed by FreeSurfer. Compared to recAN group women with acuAN showed a lower CT in multiple areas, while compared to HC they showed lower CT in temporal regions. BN group showed higher CT values in temporal and paracentral areas compared to HC. In multiple cortical areas, AcuAN group showed greater values of lGI compared to recAN group and lower values of lGI compared to HC. The BN group showed lower lGI in left medial orbitofrontal cortex compared to HC. No significant differences were found in FD among the groups. Present results provide evidence of CT and lGI alterations in patients with AN and, for the first time, in those with BN. Although these alterations could be state-dependent phenomena, they may underlie psychopathological aspects of EDs.

Background Tasting is a complex process involving chemosensory perception and cognitive evaluation. Different experimental designs and solution delivery approaches may in part explain the variability reported in literature. These technical aspects certainly limit the development of taste-related brain computer interface devices. New Method We propose a novel modular, scalable and low-cost device for rapid injection of small volumes of taste solutions during fMRI experiments that gathers the possibility to flexibly increase the number of channels, allowing complex multi-dimensional taste experiments. We provide the full description of the hardware and software architecture and illustrate the application of the working prototype in single-subject event-related fMRI experiments by showing the BOLD responses to basic taste qualities and to five intensities of tastes during the course of perception. Results The device is shown to be effective in activating multiple clusters within the gustatory pathway and a precise time-resolved event-related analysis is shown to be possible by the impulsive nature of the induced perception. Comparison with Existing Method(s) This gustometer represents the first implementation of a low-cost, easily replicable and portable device that is suitable for all kinds of fMRI taste experiments. Its scalability will boost the experimental design of more complex multi-dimensional fMRI studies of the human taste pathway. Conclusions The gustometer represents a valid open-architecture alternative to other available devices and its spread and development may contribute to an increased standardization of experimental designs in human fMRI studies of taste perception and pave the way to the development of novel taste-related BCIs.

The human gustatory cortex analyzes the chemosensory properties of tastants, particularly the quality, intensity, and affective valence, to determine whether a perceived substance should be ingested or rejected. Among previous studies, the spatial distribution of taste intensity-related activations within the human insula has been scarcely addressed. To spatially characterize a specialized or distributed nature of the cortical responses to taste intensities, a functional magnetic resonance imaging study was performed at 3 T in 44 healthy subjects where sweet and bitter tastants were administered at five increasing concentrations and cortex-based factorial and parametric analyses were performed. Two clusters in the right middle-posterior and left middle insula were found specialized for taste intensity processing, exhibiting a highly nonlinear profile across concentrations. Multiple clusters were found activated by sweet and bitter taste stimuli at most concentrations, in the anterior, middle-posterior, and inferior portion of the bilateral insula. Across these clusters, respectively, for the right and left insula, a superior-to-inferior and an anterior-to-posterior spatial gradient for high-to-low concentrations were observed for the most responsive intensity of both tastes. These findings may gather new insights regarding how the gustatory cortex is spatially organized during the perceptual processing of taste intensity for two basic tastants.

Objectives: Childhood maltreatment is a non-specific risk factor for eating disorders (EDs). However, so far, no study has assessed the impact of childhood maltreatment on brain structure of adults with EDs. Therefore, we investigated brain area volumes and fibre tract integrity of childhood maltreated (Mal) and non-maltreated (noMal) patients with EDs. Methods: Thirty-six ED women and 16 healthy women underwent an MRI scan, including acquisition of a diffusion tensor imaging (DTI) sequence and a high-resolution T1-weighted scan. ED participants were classified as Mal (18 patients) or noMal (18 patients) according to their childhood exposure to traumatic events assessed by the Childhood Trauma Questionnaire (CTQ). Results: Significantly reduced grey matter volume was detected in the right paracentral lobule and in the left inferior temporal gyrus of Mal patients. DTI analyses revealed reduced white matter integrity in the corpus callosum, internal capsule, posterior thalamic radiation, longitudinal fasciculus and corona radiata of Mal patients. Negative correlations emerged between white/grey matter changes and CTQ emotional and physical neglect scores. Conclusions: These results show that childhood trauma affects the integrity of brain structures modulating brain processes, such as reward, taste and body image perception, which play a fundamental role in the psychopathology of EDs.

Avolition, a deficit in goal-directed behavior, is a key aspect of negative symptoms. It is highly prevalent in schizophrenia and is associated to poor functional outcome and to measures of real life motivation, indicating that central to the concept is the lack of interest and motivation. In this study we tested the hypothesis that avolition is related to altered connectivity within dopaminergic cortico-striatal circuits involved in motivation processes. Since dopamine input to these circuits derives mostly from the ventro-tegmental area (VTA), we investigated the relationships between the resting-state functional connectivity (RS-FC) of the VTA and avolition in twenty-six subjects with schizophrenia (SCZ), treated with second-generation antipsychotics only, compared to twenty-two healthy controls (HC). SCZ, in comparison to HC, showed significantly reduced RS-FC of the VTA with bilateral ventro-lateral prefrontal cortex (VLPFC), bilateral insular cortex (IC) and right (R) lateral occipital complex (LOC) and increased RS-FC of the VTA with bilateral dorso-lateral prefrontal cortex (DLPFC). Significant negative correlations were found between avolition and RS-FC of the VTA with the bilateral IC, R VLPFC and R LOC. According to our findings, avolition is linked to a disconnectivity of the VTA from several key cortical regions involved in the integration of value information with action selection. These findings are in line with translational animal models of “auto-activation apathy”.

PURPOSE. Primary visual cortex (PVC) contains a retinotopic map in which the central visual field (CVF) is highly magnified compared to the peripheral field. Several studies have used functional magnetic resonance imaging (fMRI) in patients with macular degeneration to assess the reorganization of visual processing in relationship with the development of extrafoveal preferred retinal locus (PRL). We evaluated the functional response in PVC and its correlation with retinal parameters in patients with Stargardt disease due to ABCA4 mutations (STGD1). METHODS. Twenty-four STGD1 patients underwent best-corrected visual acuity, full-field standard electroretinogram (ERG), optical coherence tomography, and microperimetry. Furthermore, patients underwent fMRI to assess cerebral activation during visual stimulation by a flickering checkerboard in four PVC subdivisions, corresponding to 0° to 5° (V1), 5° to 10° (V2), 10° to 15° (V3), and 15° to 40° (V4) of CVF. RESULTS. Higher ERG responses were significantly (P < 0.0125) associated with larger functional cerebral response in V1, V2, and V3 subdivisions. Moreover, larger retinal pigment epithelium atrophy area was significantly (P < 0.0125) associated with smaller PVC activation in V2 and V3 subdivisions. Larger activation in V1 subdivision was significantly (P = 0.001) associated with higher mean macular sensitivity and smaller dense scotoma size. Finally, our results showed reduced activation in V2 and V3 with increased PRL eccentricity. CONCLUSIONS. Our study, for the first time in the literature, showed stronger PVC activation in STGD1 patients with a more preserved retinal function and macular structure. Furthermore, our study data strongly suggest that the evaluation of neuronal reorganization could be performed by considering only retinal parameters, particularly ERG responses. PURPOSE. Primary visual cortex (PVC) contains a retinotopic map in which the central visual field (CVF) is highly magnified compared to the peripheral field. Several studies have used functional magnetic resonance imaging (fMRI) in patients with macular degeneration to assess the reorganization of visual processing in relationship with the development of extrafoveal preferred retinal locus (PRL). We evaluated the functional response in PVC and its correlation with retinal parameters in patients with Stargardt disease due to ABCA4 mutations (STGD1).METHODS. Twenty-four STGD1 patients underwent best-corrected visual acuity, full-field standard electroretinogram (ERG), optical coherence tomography, and microperimetry. Furthermore, patients underwent fMRI to assess cerebral activation during visual stimulation by a flickering checkerboard in four PVC subdivisions, corresponding to 0 degrees to 5 degrees (V1), 5 degrees to 10 degrees (V2), 10 degrees to 15 degrees (V3), and 15 degrees to 40 degrees (V4) of CVF.RESULTS. Higher ERG responses were significantly (P < 0.0125) associated with larger functional cerebral response in V1, V2, and V3 subdivisions. Moreover, larger retinal pigment epithelium atrophy area was significantly (P < 0.0125) associated with smaller PVC activation in V2 and V3 subdivisions. Larger activation in V1 subdivision was significantly (P = 0.001) associated with higher mean macular sensitivity and smaller dense scotoma size. Finally, our results showed reduced activation in V2 and V3 with increased PRL eccentricity.CONCLUSIONS. Our study, for the first time in the literature, showed stronger PVC activation in STGD1 patients with a more preserved retinal function and macular structure. Furthermore, our study data strongly suggest that the evaluation of neuronal reorganization could be performed by considering only retinal parameters, particularly ERG responses.

The avolition/apathy domain of negative symptoms includes motivation- and pleasure-related impairments. In people with schizophrenia, structural and functional abnormalities were reported in key regions within the motivational reward system, including ventral-tegmental area (VTA), striatum (especially at the level of the nucleus accumbens, NAcc), orbitofrontal cortex (OFC), as well as amygdala (Amy) and insular cortex (IC). However, the association of the reported abnormalities with avoliton-apathy is still controversial. In the present study, we investigated white matter connectivity patterns within these regions, using a probabilistic analysis of diffusion tensor imaging (DTI) data, in male subjects with schizophrenia. Thirty-five male subjects with schizophrenia (SCZ) and 17 male healthy controls (HC) matched for age, underwent DTI. SCZ were evaluated using the Schedule for Deficit Syndrome (SDS), the Positive and Negative Syndrome Scale (PANSS), and the MATRICS Consensus Cognitive Battery (MCCB). Probabilistic tractography was applied to investigate pathways connecting the Amy and the NAcc with the OFC and IC. Reduced fractional anisotropy (FA) was observed in left Amy–ventral anterior IC connections, in SCZ compared with controls. This abnormality was negatively correlated with avolition/apathy but not with expressive deficit scores. SCZ showed also a reduced connectivity index between right NAcc and medial OFC, as compared with controls. Finally, the left NAcc-dorsal anterior IC connectivity index was negatively correlated with working memory scores. Our results indicate that only the avolition/apathy domain of negative symptoms is related to abnormal connectivity in the motivation-related circuits. The findings also demonstrate that distinct alterations underlie cognitive impairment and avolition/apathy.

Non-alcoholic fatty liver disease is becoming a global epidemic. The aim of this study was to develop a system for assessing liver fat content based on ultrasound images. Magnetic resonance spectroscopy measurements were obtained in 61 patients and the controlled attenuation parameter in 54. Ultrasound images were acquired for all 115 participants and used to calculate the hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization. The Steato-score was obtained by combining these five parameters. Magnetic resonance spectroscopy measurements were significantly correlated with hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization; Steato-score was dependent on hepatic/renal ratio, attenuation rate and diaphragm visualization. Area under the receiver operating characteristic curve was equal to 0.98, with 89% sensitivity and 94% specificity. Controlled attenuation parameter values were significantly correlated with hepatic/renal ratio, attenuation rate, diaphragm visualization and Steato-score; the area under the curve was 0.79. This system could be a valid alternative as a non-invasive, simple and inexpensive assessment of intrahepatic fat.

The presence of significant fibrosis is an indicator for liver disease staging and prognosis. The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14-16.7 kPa and were 4.49 kPa and 2.92-7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87-0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity.

Functional magnetic resonance imaging (fMRI) studies have displayed a dysregulation in the way in which the brain processes pleasant taste stimuli in patients with anorexia nervosa (AN) and bulimia nervosa (BN). However, exactly how the brain processes disgusting basic taste stimuli has never been investigated, even though disgust plays a role in food intake modulation and AN and BN patients exhibit high disgust sensitivity. Therefore, we investigated the activation of brain areas following the administration of pleasant and aversive basic taste stimuli in symptomatic AN and BN patients compared to healthy subjects. Twenty underweight AN women, 20 symptomatic BN women and 20 healthy women underwent fMRI while tasting 0.292 M sucrose solution (sweet taste), 0.5 mM quinine hydrochloride solution (bitter taste) and water as a reference taste. In symptomatic AN and BN patients the pleasant sweet stimulus induced a higher activation in several brain areas than that induced by the aversive bitter taste. The opposite occurred in healthy controls. Moreover, compared to healthy controls, AN patients showed a decreased response to the bitter stimulus in the right amygdala and left anterior cingulate cortex, while BN patients showed a decreased response to the bitter stimulus in the right amygdala and left insula. These results show an altered processing of rewarding and aversive taste stimuli in ED patients, which may be relevant for understanding the pathophysiology of AN and BN.

Background Right insular cortex is involved in taste discrimination, but its functional organization is still poorly known. In general, sensory cortices represent the spatial prevalence of relevant features for each sensory modality (visual, auditory, somatosensory) in an ordered way across the cortical space. Following this analogy, we hypothesized that primary taste cortex is organized in similar ordered way in response to six tastes with known receptorial mechanisms (sweet, bitter, sour, salt, umami, CO2). Design Ten normal subjects were enrolled in a pilot study. We used functional magnetic resonance imaging (fMRI), a high resolution cortical registration method, and specialized procedures of feature prevalence localization, to map fMRI responses within the right insular cortex, to water solutions of quinine hydrochloride (bitter), Acesulfamate K (sweet), sodium chloride (salt), mono potassium glutamate + inosine 5' mono phosphate (Umami), citric acid (sour) and carbonated water (CO2). During an fMRI scan delivery of the solutions was applied in pseudo-random order interleaved with cleaning water. Results Two subjects were discarded due to excessive head movements. In the remaining subjects, statistically significant activations were detected in the fMRI responses to all tastes in the right insular cortex (p

The functional interplay between hemispheres is fundamental for behavioral, cognitive, and emotional control. Anorexia nervosa (AN) and bulimia nervosa (BN) have been largely studied with brain magnetic resonance imaging (MRI) in relation to the functional mechanisms of high-level processing, but not in terms of possible inter-hemispheric functional connectivity anomalies. Using resting-state functional MRI (fMRI), voxel-mirrored homotopic connectivity (VMHC) and regional inter-hemispheric spectral coherence (IHSC) were studied in 15 AN and 13 BN patients and 16 healthy controls (HC). Using T1-weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left-right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA). Compared to HC, AN patients exhibited reduced VMHC in cerebellum, insula, and precuneus, while BN patients showed reduced VMHC in dorso-lateral prefrontal and orbito-frontal cortices. The regional IHSC analysis highlighted that the inter-hemispheric functional connectivity was higher in the ‘Slow-5’ band in all regions except the insula. No group differences in left–right structural asymmetries and in VMHC vs. callosal FA correlations were significant in the comparisons between cohorts. These anomalies, not explained by structural changes, indicate that AN and BN, at least in their acute phase, are associated with a loss of inter-hemispheric connectivity in regions implicated in self-referential, cognitive control and reward processing. These findings may thus gather novel functional markers to explore aberrant features of these eating disorders.

Background & Aims Short-term studies have shown that somatostatin analogues are effective in patients with polycystic kidney and liver disease. We evaluated the long-term effects of long-acting release octreotide (octreotide LAR), a somatostatin inhibitor, vs placebo in these patients. Methods We performed a controlled study of adults with polycystic kidney and liver disease (estimated glomerular filtration rate, 40 mL/min/1.73m 2 or more) at a single center in Italy. We analyzed data from 27 patients randomly assigned to groups given octreotide LAR (40 mg, n = 14) or placebo (n = 13) each month for 3 years. The primary outcome was absolute and percentage change in total liver volume (TLV), which was measured by magnetic resonance imaging at baseline, after 3 years of treatment, and then 2 years after treatment ended. Results Baseline characteristics were similar between groups. After 3 years, TLV decreased by 130.2 ± 133.2 mL in patients given octreotide LAR (7.8% ± 7.4%) ( P = .003) but increased by 144.3 ± 316.8 mL (6.1% ± 14.1%) in patients given placebo. Change vs baseline differed significantly between groups ( P = .004). Two years after treatment ended, TLV had decreased 14.4 ± 138.4 mL (0.8% ± 9.7%) from baseline in patients given octreotide LAR but increased by 224.4 ± 331.7 mL (11.0% ± 14.4%) in patients given placebo. Changes vs baseline still differed significantly between groups ( P = .046). Decreases in TLV were similar in each sex; the change in TLV was greatest among subjects with larger baseline TLV. No patient withdrew because of side effects. Conclusions In a placebo-controlled study of patients with polycystic kidney and liver disease, 3 years of treatment with octreotide LAR significantly reduced liver volume; reductions were maintained for 2 years after treatment ended. Octreotide LAR was well-tolerated. ClinicalTrials.gov number: NCT02119052.

Background – No head-to-head study has been performed yet to assess whether natalizumab is more effective than classical immunomodulators in multiple sclerosis (MS). Aim – To retrospectively compare the efficacy of natalizumab vs IFN beta 1a SC (44 μg; Rebif®) on clinical and radiological findings in two matched cohorts of patients with MS. Patients and methods – We retrospectively enrolled two cohorts of 42 patients (F/M: 35/7) with relapsing-remitting multiple sclerosis treated with natalizumab or IFN beta 1a for at least 12 consecutive months. Outcome measures were annualized relapse rate (ARR), changes in expanded disability status scale (EDSS) score, and number of contrast-enhancing lesions (CELs) at magnetic resonance imaging (MRI). Results – In both groups, the ARR in the 12 months of treatment was lower than in the 12 months before therapy (0.24 vs 1.50 in natalizumab-treated group, P

Background: Insulin-like growth factor (IGF)-I has a role in remyelination, and insulin-like growth factor-binding protein-3 (IGFBP-3) might reduce its bioavailability. A role of IGFBP-3 in multiple sclerosis (MS) progression was hypothesized in patients with primary progressive (PP) MS. Objective: To evaluate serum levels of IGF-I and IGFBP-3 in patients with relapsing–remitting (RR) and secondary progressive (SP) MS and their correlations with disease activity and progression. Methods: Sixty-three (41 RR and 22 SP) ‘naive’ MS patients and 60 age-matched healthy controls were enrolled. Patients were assessed through clinical [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), number of relapses] and laboratory investigations. IGF-I and IGFBP-3 were measured by ELISA. Results: Levels of IGF-I and IGFBP-3 were similar in the two MS groups. IGFBP-3 levels were higher in patients with MS than in controls (P

Eur J Clin Invest 2010; 41 (1): 39–44 Abstract Background Fatty liver is commonly associated with insulin-resistant conditions, often related to increased abdominal visceral fat. Our objective was to elucidate the specific roles of obesity, type 2 diabetes mellitus, insulin-resistance and abdominal fat distribution. Materials and methods The study population comprised 13 diabetic obese (DO), 10 nondiabetic obese (NDO), and nine normal-weight control (C) men aged 28–65 years, with normal plasma triglyceride levels. DO were in good glycaemic control (HbA1c = 6·8 ± 0·8%) (M ± SD) with diet (n = 8) or diet + metformin (n = 5). Liver fat content was measured by 1H-magnetic resonance spectroscopy, abdominal fat distribution by magnetic resonance imaging and insulin sensitivity by hyperinsulinaemic euglycaemic clamp. Results DO and NDO subjects had similar whole-body insulin resistance, BMI and waist circumference, higher than those of C subjects (P

BackgroundThe neurobiological underpinnings of avolition in schizophrenia remain unclear. Most brain imaging research has focused on reward prediction deficit and on ventral striatum dysfunction, but findings are not consistent. In the light of accumulating evidence that both ventral striatum and dorsal caudate play a key role in motivation, we investigated ventral striatum and dorsal caudate activation during processing of reward or loss in patients with schizophrenia.MethodWe used functional magnetic resonance imaging to study brain activation during a Monetary Incentive Delay task in patients with schizophrenia, treated with second-generation antipsychotics only, and in healthy controls (HC). We also assessed the relationships of ventral striatum and dorsal caudate activation with measures of hedonic experience and motivation.ResultsThe whole patient group had lower motivation but comparable hedonic experience and striatal activation than HC. Patients with high avolition scores showed lower dorsal caudate activation than both HC and patients with low avolition scores. A lower dorsal caudate activation was also observed in patients with deficit schizophrenia compared to HC and patients with non-deficit schizophrenia. Dorsal caudate activity during reward anticipation was significantly associated with avolition, but not with anhedonia in the patient group.ConclusionsThese findings suggest that avolition in schizophrenia is linked to dorsal caudate hypoactivation.

PURPOSE. To assess whether and to what extent macro- and/or microstructural modifications are present in the brain of patients with selective central visual loss due to a juvenile macular degeneration, Stargardt's disease (STGD), taking advantage of the complementary information provided by voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). METHODS. Eighteen patients with clinical and molecular diagnosis of STGD related to ABCA4 mutations and 23 normally sighted volunteers of comparable age and sex were enrolled. Structural T1-weighted (T1w) volumes, for brain tissue volume assessment by segmentation, and DTI, for the investigation of diffusivity parameters via a tract-based spatial statistics (TBSS) procedure, were acquired at 3 Tesla in all subjects. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), biomicroscopy, ophthalmoscopy, electroretinography (ERG), microperimetry, and optical coherence tomography (OCT). Correlations between imaging data and clinical measures were tested. RESULTS. Stargardt's disease patients showed a significant gray matter (GM) loss bilaterally in the occipital cortices, extending into the right precuneus, and in the fronto-orbital cortices. At TBSS, significant reductions in fractional anisotropy were detected throughout large regions in the supratentorial white matter (WM), more pronounced in the posterior areas. Gray matter volume correlated directly with mean visual sensitivity in the right middle frontal and left calcarine gyri, and inversely with retinal thickness in the left supramarginal gyrus. CONCLUSIONS. In STGD, widespread microstructural WM alterations are present, suggestive of minor fiber loss coupled with GM loss, also in cortical regions not traditionally linked to visual pathways, at least partly related to the retinal damage. Purpose: To assess whether and to what extent macro- and/or microstructural modifications are present in the brain of patients with selective central visual loss due to a juvenile macular degeneration, Stargardt’s disease (STGD), taking advantage of the complementary information provided by voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). Methods: Eighteen patients with clinical and molecular diagnosis of STGD related to ABCA4 mutations and 23 normally sighted volunteers of comparable age and sex were enrolled. Structural T1-weighted (T1w) volumes, for brain tissue volume assessment by segmentation, and DTI, for the investigation of diffusivity parameters via a tract-based spatial statistics (TBSS) procedure, were acquired at 3 Tesla in all subjects. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), biomicroscopy, ophthalmoscopy, electroretinography (ERG), microperimetry, and optical coherence tomography (OCT). Correlations between imaging data and clinical measures were tested. Results: Stargardt’s disease patients showed a significant gray matter (GM) loss bilaterally in the occipital cortices, extending into the right precuneus, and in the fronto-orbital cortices. At TBSS, significant reductions in fractional anisotropy were detected throughout large regions in the supratentorial white matter (WM), more pronounced in the posterior areas. Gray matter volume correlated directly with mean visual sensitivity in the right middle frontal and left calcarine gyri, and inversely with retinal thickness in the left supramarginal gyrus. Conclusions: In STGD, widespread microstructural WM alterations are present, suggestive of minor fiber loss coupled with GM loss, also in cortical regions not traditionally linked to visual pathways, at least partly related to the retinal damage.

Recently introduced hybrid PET/MR scanners provide the opportunity to measure simultaneously, and in direct spatial correspondence, both metabolic demand and functional activity of the brain, hence capturing complementary information on the brain's physiological state. Here we exploited PET/MR simultaneous imaging to explore the relationship between the metabolic information provided by resting-state fluorodeoxyglucose-PET (FDG-PET) and fMRI (rs-fMRI) in neurologically healthy subjects. Regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and degree of centrality (DC) maps were generated from the rs-fMRI data in 23 subjects, and voxel-wise comparison to glucose uptake distribution provided by simultaneously acquired FDG-PET was performed. The mutual relationships among each couple of these four metrics were explored in terms of similarity, both of spatial distribution across the brain and the whole group, and voxel-wise across subjects, taking into account partial volume effects by adjusting for grey matter (GM) volume. Although a significant correlation between the spatial distribution of glucose uptake and rs-fMRI derived metrics was present, only a limited percentage of GM voxels correlated with PET across subjects. Moreover, the correlation between the spatial distributions of PET and rs-fMRI-derived metrics is spatially heterogeneous across both anatomic regions and functional networks, with lowest correlation strength in the limbic network (Spearman rho around -0.11 for DC), and strongest correlation for the default-mode network (up to 0.89 for ReHo and 0.86 for fALFF). Overall, ReHo and fALFF provided significantly higher correlation coefficients with PET (p=10(-8) and 10(-7), respectively) as compared to DC, while no significant differences were present between ReHo and fALFF. Local GM volume variations introduced a limited overestimation of the rs-fMRI to FDG correlation between the modalities under investigation through partial volume effects. These novel results provide the basis for future studies of alterations of the coupling between brain metabolism and functional connectivity in pathologic conditions.

a b s t r a c t The prevalence of fatty liver (steatosis) in the general population is rapidly increasing worldwide. The progress of knowledge in the physiopathology of fatty liver is based on the systems biology approach to studying the complex interactions among different physiological systems. Similarly, translational and clinical research should address the complex interplay between these systems impacting on fatty liver. The clinical needs drive the applications of systems medicine to re-define clinical phenotypes, assessing the multiple nature of disease susceptibility and progression (e.g. the definition of risk, prognosis, diag- nosis criteria, and new endpoints of clinical trials). Based on this premise and in light of recent findings, the complex mechanisms involved in the pathology of fatty liver and their impact on the short- and long- term clinical outcomes of cardiovascular, metabolic liver diseases associated with steatosis are presented in this review using a new "systems medicine" approach. A new data set is proposed for studying the impairments of different physiological systems that have an impact on fatty liver in different subsets of subjects and patients.

The five universally accepted tastes, sweet, salty, sour, bitter, and umami (a savory sensation elicited by monosodium glutamate) have specific receptors in oral, pharyngeal and laryngeal regions [1]. The most credited candidates to the function of human primary taste cortex are the frontal operculum and the anterior insula; while the opercular cortex and the orbitofrontal cortex are thought to code for secondary gustatory functions, while the amygdale and the dorsolateral prefrontal cortex are involved as hierarchically superior processing units [2]. Conversely, more is known on the peripheral pathway of taste, including the molecular dynamics of many receptors [3].

Interpretation of brain positron emission tomography (PET) in terms of function vs. structure is ambiguous owing to the partial volume effect (PVE). Therefore, observed differences in tracer distribution could reflect differences in either activity or volume, a problem that applies principally to gray matter (GM) since white matter (WM) virtually always has uniform activity. To assess the contribution of GM volume vs. activity, we implemented a method to directly compare PET images with underlying structure, and applied it to resting-state (18)Fluoro-deoxy-glucose-PET (FDG) of healthy subjects. Methods. Average GM and WM PVE-corrected mean FDG uptake values were applied onto co-registered segmented magnetic resonance imaging data sets to generate a "virtual PET" in which activity is proportional to GM volume and resolution set to that of PET. The raw PET and virtual PET values were then compared across the sample of subjects, first voxel-wise to detect clusters with significant activity-volume mismatch, and second within regions-of-interest (ROI) to quantify mismatches between unsmoothed voxel values. Results. Relative to volume, there was significant hyperactivity of most GM structures of the dorsal brain-except the thalamus-and significant hypoactivity of the temporal lobe, hippocampal region, and cerebellum, consistent across the voxel- and ROI-based analyses. Conclusion. As applied to normals, our method documented the expected contribution of functional activity independently of local differences in GM volume in the normal pattern of FDG uptake, and disclosed marked heterogeneities in functional activity per unit GM volume among structures. This generic method should find applications in pathological states as well as for other PET and SPECT radiotracers.

IntroductionTaste perception is a complex phenomenon modulated by different factors, such as taste receptors and memory brain circuits. The palatability of the food, that activates the central reward pathways, also plays an important role in taste perception. It means that taste is able to influence the choice of food and then eating behaviour.ObjectivesIt is well known that people with anorexia nervosa (AN) have a lower sensitivity to reward stimuli and recent studies suggested that altered function of taste neural circuitry may contribute to restricted eating in AN.AimsThe aim of this study was to evaluate, in patients suffering from AN, the activation of brain areas involved in taste perception and in central reward mechanisms to both pleasant and aversive taste stimuli and to correlate gustatory neurocircuitry activity with eating behaviours, temperament measures and/or sensitivity to reward and to punishment.MethodsFifteen underweight female AN patients and sixteen normal-weight healthy women underwent a functional MRI to measure brain areas activation to repeated stimuli of a pleasant taste (sucrose solution), alternated with an aversive taste (bitter solution), and water taste.ResultsCompared to healthy controls, patients with AN showed a significantly reduced activation of left insula and left dorsolateral prefrontal cortex to sweet stimulus and reduced activation of right parietal cortex to bitter stimulus.ConclusionsThese results, if confirmed in future studies, may improve our knowledge about the pathophysiological mechanisms of AN.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionThe functional interplay between brain hemispheres is fundamental for behavioral, cognitive and emotional control. Several pathophysiological aspects of eating disorders (EDs) have been investigated by the use of functional Magnetic Resonance Imaging (fMRI).ObjectivesThe objective of the study was to investigate functional brain asymmetry of resting-state fMRI correlations in symptomatic patients with anorexia nervosa (AN) and bulimia nervosa (BN).AimsWe aimed at revealing whether brain regions implicated in reward, cognitive control, starvation and emotion regulation show altered inter-hemispheric functional connectivity in patients with AN and BN.MethodsUsing resting-state fMRI, voxel-mirrored homotopic connectivity (VMHC) and regional inter-hemispheric spectral coherence (IHSC) analyses in two canonical slow frequency bands (“Slow-5”, “Slow-4”) were studied in 15AN and 13BN patients and 16 healthy controls (HC). Using T1-weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left-right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA).ResultsCompared to HC, AN patients exhibited reduced VMHC in cerebellum, insula and precuneus, while BN patients showed reduced VMHC in dorso-lateral prefrontal and orbito-frontal cortices. The regional IHSC analysis highlighted that the inter-hemispheric functional connectivity was higher in the ‘Slow-5′Band in all regions except the insula. No group differences in left-right structural asymmetries and in VMHC vs callosal FA correlations were found.ConclusionsThese anomalies indicate that AN and BN, at least in their acute phase, are associated with a loss of inter-hemispheric connectivity in regions implicated in self-referential, cognitive control and reward processing.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The heartbeat has been proposed as an intrinsic source of motion that can be used in combination with tagged Magnetic Resonance Imaging (MRI) to measure displacements induced in the liver as an index of liver stiffness. Optimizing a tagged MRI acquisition protocol in terms of sensitivity to these displacements, which are in the order of pixel size, is necessary to develop the method as a quantification tool for staging fibrosis. We reproduced a study of cardiac-induced strain in the liver at 3T and simulated tagged MR images with different grid tag patterns to evaluate the performance of the Harmonic Phase (HARP) image analysis method and its dependence on the parameters of tag spacing and grid angle. The Partial Volume Effect (PVE), T1 relaxation, and different levels of noise were taken into account. Four displacement fields of increasing intensity were created and applied to the tagged MR images of the liver. These fields simulated the deformation at different liver stiffnesses. An Error Index (EI) was calculated to evaluate the estimation accuracy for various parameter values. In the absence of noise, the estimation accuracy of the displacement fields increased as tag spacings decreased. EIs for each of the four displacement fields were lower at 0 degrees and the local minima of the EI were found to correspond to multiples of pixel size. The accuracy of the estimation decreased for increasing levels of added noise; as the level increased, the improved estimation caused by decreasing the tag spacing tended to zero. The optimal tag spacing turned out to be a compromise between the smallest tag period that is a multiple of the pixel size and is achievable in a real acquisition and the tag spacing that guarantees an accurate liver displacement measure in the presence of realistic levels of noise.

Approximately 30% of schizophrenia patients do not respond adequately to the therapy. Previous MRI studies have suggested that drug treatment resistance is associated with brain morphological abnormalities, although region-of-interest analysis of MR studies from nonresponder and responder patients failed to demonstrate a statistically significant difference between these two schizophrenia subgroups. We have used a voxel-based analysis of segmented MR studies to assess structural cerebral differences in 20 nonresponder and 15 responder patients and 16 age-matched normal volunteers. Differences between the three groups emerged bilaterally mainly at the level of the superior and middle frontal gyri, primarily due to reduced grey matter volumes in nonresponders, as compared to both normal volunteers and responder patients. Post hoc direct comparison between the two schizophrenia subgroups demonstrated significantly reduced grey matter volumes in middle frontal gyrus bilaterally, in the dorsolateral aspects of left superior frontal gyrus extending into postcentral gyrus and in the right medial temporal cortex. Our results extend and integrate previous findings suggesting a more severe atrophy in nonresponder schizophrenia patients, compared to responder patients, mainly at the level of the superior and middle frontal gyri. Longitudinal studies in drug-naïve patients are needed to assess the role of these associations.

One of the most important issues in blood-oxygen-level-dependent (BOLD)-based brain functional magnetic resonance imaging is the understanding of the vascular structures that are responsible for the signal changes observed. The T2*-related signal changes observed during variations in susceptibility-induced magnetic field gradients are a function both of non-refocusable mechanisms, such as diffusion, and of refocusable effects such as field inhomogeneities. Conversely, T2-related signal changes are only a function of non-refocusable effects. It has been suggested that T2-weighted images could be less sensitive to blood susceptibility changes in a macrovascular environment than T2*-weighted images and could thus be more accurate in identifying the "activation" of the parenchyma rather than "draining vein" effects. In this study we use hypoxia and hypercapnia challenges in cats to provide a change in blood deoxyhemoglobin concentration (as a model for classic BOLD changes and not as a model for neuronal activation). A combined gradient echo and spin echo echo-planar-imaging (EPI) pulse sequence was used to map DeltaR2 (i.e., Delta(1/T2)) and DeltaR2* (i.e., Delta(1/T2*)) changes during the challenges. Our experiments demonstrate that: (i) the acquisition of T2-weighted EPI data does not in itself differentiate signal changes in the parenchyma from those occurring in regions around larger vessels, but that (ii) the simultaneous acquisition of T2- and T2*-weighted images could be useful in identifying microvascular regions in gray matter by analyzing the ratio DeltaR2/DeltaR2*. This value seems independent of the degree of deoxyhemoglobin concentration change, but is related to properties of the vascular environment. We suggest a possible application of the results to the study of brain function in humans.

In this study, changes in blood oxygenation and volume were monitored while monolingual right-handed subjects read English sentences. Our results confirm the role of the left peri-sylvian cortex in language processing. Interestingly, individual subject analyses reveal a pattern of activation characterized by several small, limited patches rather than a few large, anatomically well-circumscribed centers. Between-subject analyses confirm a lateralized pattern of activation and reveal active classical language areas including Broca's area, Wernicke's area, and the angular gyms. In addition they point to areas only more recently considered as language-relevant including the anterior portion of the superior temporal sulcus. This area has not been reliably observed in imaging studies of isolated word processing. This raises the hypothesis that activation in this area is dependent on processes specific to sentence reading.

Background: Ataxia-Teleangiectasia (A-T) is a rare neurodegenerative disorder characterized by progressive cerebellar degeneration. Till few years ago only supportive care was available to improve the neurological function in A-T patients. Even though A-T remains an incurable disease, we recently demonstrated a drug dependent amelioration of neurological signs in A-T patients during a short-term treatment with oral betamethasone. Aims: The aim of this study is to evaluate whether the steroid induced motor performance changes in A-T are associated with functional magnetic resonance imaging (fMRI) modifications. This represents a preliminary pilot study, which requires a validation on a larger cohort of patients. Methods: Six A-T patients received a 10-days cycle of oral betamethasone at 0.03 mg/kg/day. fMRI studies were carried out at T0 and at the end of the cycle. The neurological evaluation was performed through the Scale for the Assessment and Rating of Ataxia (SARA) quantification. The fMRI protocol was a block design with alternating epochs of rest and pronosupination of the dominant (right) hand. Results: The voxel-based comparison showed a remarkable increase in the number of activated voxels within the motor cortex under the on-therapy condition as compared with the cortical activity under baseline condition in the 2 patients who completed the study protocol. Conclusions: Changes in motor performance in A-T patients treated with betamethasone are coupled with an increase in the activation in relevant cortical areas, thus suggesting that in A-T patients steroid treatment could improve motor performance facilitating cortical compensatory mechanisms.

Little is known about how CO2 affects neural processing of taste. We used functional magnetic resonance imaging to investigate the effects of carbonation on brain processing of sweet stimuli, which has relevance to studies of food selection and satiety. The presence of carbonation produced an overall decrease in the neural processing of sweetness-related signals, especially from sucrose. CO2 reduced the neural processing of sucrose more than that of artificial sweeteners. These findings might be relevant to dietary interventions that include noncaloric beverages, whereas the combination of CO2 and sucrose might increase consumption of sucrose.

Progressive prosopagnosia (PP) is a clinical syndrome characterized by a progressive and selective inability to recognize and identify faces of familiar people. Here we report a patient (G.S.) with PP, mainly related to a prominent deficit in recognition of familiar faces, without a semantic (cross-modal) impairment. An in-depth evaluation showed that his deficit extended to other classes of objects, both living and non-living. A follow-up neuropsychological assessment did not reveal substantial changes after about 1 year. Structural MRI showed predominant right temporal lobe atrophy.\ud \ud Diffusion tensor imaging was performed to elucidate structural connectivity of the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), the two major tracts that project through the core fusiform region to the anterior temporal and frontal cortices, respectively. Right ILF was markedly reduced in G.S., while left ILF and IFOFs were apparently preserved. These data are in favour of a crucial role of the neural circuit subserved by right ILF in the pathogenesis of PP.

OBJECTIVE To evaluate the effects of qualitative dietary changes and the interaction with aerobic exercise training on liver fat content independent of weight loss in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS With use of a factorial 2 × 2 randomized parallel-group design, 37 men and 8 women, aged 35–70 years, with type 2 diabetes in satisfactory blood glucose control on diet or diet plus metformin treatment were assigned to one of the following groups for an 8-week period: 1) high-carbohydrate/high-fiber/low–glycemic index diet (CHO/fiber group), 2) high-MUFA diet (MUFA group), 3) high-carbohydrate/high-fiber/low–glycemic index diet plus physical activity program (CHO/fiber+Ex group), and 4) high-MUFA diet plus physical activity program (MUFA+Ex group). Before and after intervention, hepatic fat content was measured by 1H NMR. RESULTS Dietary compliance was optimal and body weight remained stable in all groups. Liver fat content decreased more in MUFA (−29%) and MUFA+Ex (−25%) groups than in CHO/fiber (−4%) and CHO/fiber+Ex groups (−6%). Two-way repeated-measures ANOVA, including baseline values as covariate, showed a significant effect on liver fat content for diet (P = 0.006), with no effects for exercise training (P = 0.789) or diet-exercise interaction (P = 0.712). CONCLUSIONS An isocaloric diet enriched in MUFA compared with a diet higher in carbohydrate and fiber was associated with a clinically relevant reduction of hepatic fat content in type 2 diabetic patients independent of an aerobic training program and should be considered for the nutritional management of hepatic steatosis in people with type 2 diabetes.

Knowledge of the exact spatial distribution of brain tissues in images acquired by magnetic resonance imaging (MRI) is necessary to measure and compare the performance of segmentation algorithms. Currently available physical phantoms do not satisfy this requirement. State-of-the-art digital brain phantoms also fall short because they do not handle separately anatomical structures (e.g. basal ganglia) and provide relatively rough simulations of tissue fine structure and inhomogeneity. We present a software procedure for the construction of a realistic MRI digital brain phantom. The phantom consists of hydrogen nuclear magnetic resonance spin-lattice relaxation rate (R1), spin-spin relaxation rate (R2), and proton density (PD) values for a 24 x 19 x 15.5 cm volume of a ''normal'' head. The phantom includes 17 normal tissues, each characterized by both mean value and variations in R1, R2, and PD. In addition, an optional tissue class for multiple sclerosis (MS) lesions is simulated. The phantom was used to create realistic magnetic resonance (MR) images of the brain using simulated conventional spin-echo (CSE) and fast field-echo (FFE) sequences. Results of mono-parametric segmentation of simulations of sequences with different noise and slice thickness are presented as an example of possible applications of the phantom. The phantom data and simulated images are available online at http://lab.ibb.cnr.it/.

A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing—remitting multiple sclerosis patients, aged 18—50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 µg (three times weekly) for 12 months, were randomized to combination therapy (interferon + atorvastatin 20 mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A ( n = 21) or B ( n = 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline ( p = 0.007) and significantly fewer relapses versus the two pre-randomization years ( p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p = 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone.

Previous studies have shown a preferential loss of grey matter in fronto-temporal regions in patients with multiple sclerosis. Studies of correlates of disease severity are more controversial, because some studies have suggested an association between sensorimotor cortex atrophy and Expanded Disability Status Scale score, while others did not find such a correlation. The objective of this study was to assess the correlation of regional loss of grey matter and white matter with indexes of clinical and radiological severity in relapsing—remitting multiple sclerosis, including the Expanded Disability Status Scale and lesion load. Correlations between Expanded Disability Status Scale, lesion load and disease duration were assessed in 128 patients with relapsing—remitting multiple sclerosis (Expanded Disability Status Scale range 1.0—6.0) using optimized voxel-based morphometry. Bilateral loss of grey matter in sensorimotor cortices was correlated with Expanded Disability Status Scale, and tissue loss also involved adjacent white matter, extending along pyramidal tracts to the brainstem. Increasing lesion load was correlated with loss of deep grey matter and white matter. No specific region of grey matter or white matter showed a significant correlation with disease duration. These findings support the hypothesis that motor neuron involvement plays a major role in the progression of physical disability. Lesion load accrual affects mainly highly interconnected subcortical structures, while disease duration has a less significant impact on brain atrophy, probably owing to the inter-subject heterogeneity of the clinical course of the disease.

Background To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. Methods Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. Results The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. Conclusions In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.

The aim of this study was to determine the diagnostic performance of Ultrasound (US) in the quantitative assessment of steatosis by comparison with Proton Magnetic Resonance Spectroscopy (1H-MRS) as a...

The aim of this study was to determine the diagnostic performance of ultrasound (US) in the quantitative assessment of steatosis by comparison with proton magnetic resonance spectroscopy ((1)H-MRS) as a reference standard. Three liver echo-intensity indices were derived: US hepatic mean gray level, hepatic-renal echo-intensity ratio (H/R), and hepatic-portal blood echo-intensity ratio. The (1)H-MRS degree of steatosis was determined as percentage fat by wet weight. Regression equations were used to estimate quantitatively hepatic fat content. The hepatic fat content by (1)H-MRS analysis ranged from 0.10% to 28.9% (median value, 4.8%). Ultrasound H/R was correlated with the degree of steatosis on (1)H-MRS (R(2)= 0.92; P < .0001), whereas no correlation with (1)H-MRS was found for hepatic mean gray level and hepatic-portal blood echo-intensity ratio. A receiver operating characteristic curve identified the H/R of 2.2 as the best cutoff point for the prediction of (1)H-MRS of at least 5%, yielding measures of sensitivity and specificity of 100% and 95%, respectively. In this pilot study, US H/R exhibits high sensitivity and specificity for detecting liver fatty changes. Our results indicate that quantitative evaluation of hepatic fat content can be performed using US H/R and could therefore be a valuable analytic tool in clinical investigation.