Sex differences in the taste-evoked functional connectivity network.

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.

Dietary influence on adiponectin in patients with type 2 diabetes.

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 1 H 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 µg/mL vs. 10.8 ± 2.3 µg/mL; P = .033) but not after the MUFA diet (10.6 ± 1.8 µg/mL vs. 10.6 ± 1.6 µg/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.

Intensity-related distribution of sweet and bitter taste fMRI responses in the insular cortex.

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.

Interhemispheric functional connectivity in anorexia and bulimia nervosa.

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.

Long-term Effects of Octreotide on Liver Volume in Patients With Polycystic Kidney and Liver Disease.

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.

Relationship between simultaneously acquired resting-state regional cerebral glucose metabolism and functional MRI: a PET/MR hybrid scanner study.

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.

Effect of carbonation on brain processing of sweet stimuli in humans.

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.

Role of advanced imaging techniques in the evaluation of oncological therapies in patients with colorectal liver metastases.

In patients with colorectal liver metastasis (CRLMs) unsuitable for surgery, oncological treatments, such as chemotherapy and targeted agents, can be performed. Cross-sectional imaging [computed tomography (CT), magnetic resonance imaging (MRI), 18-fluorodexoyglucose positron emission tomography with CT/MRI] evaluates the response of CRLMs to therapy, using post-treatment lesion shrinkage as a qualitative imaging parameter. This point is critical because the risk of toxicity induced by oncological treatments is not always balanced by an effective response to them. Consequently, there is a pressing need to define biomarkers that can predict treatment responses and estimate the likelihood of drug resistance in individual patients. Advanced quantitative imaging (diffusion-weighted imaging, perfusion imaging, molecular imaging) allows the in vivo evaluation of specific biological tissue features described as quantitative parameters. Furthermore, radiomics can represent large amounts of numerical and statistical information buried inside cross-sectional images as quantitative parameters. As a result, parametric analysis (PA) translates the numerical data contained in the voxels of each image into quantitative parameters representative of peculiar neoplastic features such as perfusion, structural heterogeneity, cellularity, oxygenation, and glucose consumption. PA could be a potentially useful imaging marker for predicting CRLMs treatment response. This review describes the role of PA applied to cross-sectional imaging in predicting the response to oncological therapies in patients with CRLMs.

Functional MRI activation of the nucleus tractus solitarius after taste stimuli at ultra-high field: a proof-of-concept single-subject study.

Using ultra-high field (7 Tesla) functional MRI (fMRI), we conducted the first in-vivo functional neuroimaging study of the normal human brainstem specifically designed to examine neural signals in the Nucleus Tractus Solitarius (NTS) in response to all basic taste stimuli. NTS represents the first relay station along the mammalian taste processing pathway which originates at the taste buds in the oral cavity and passes through the thalamus before reaching the primary taste cortex in the brain. In our proof-of-concept study, we acquired data from one adult volunteer using fMRI at 1.2 mm isotropic resolution and performed a univariate general linear model analysis. During fMRI acquisition, three shuffled injections of sweet, bitter, salty, sour, and umami solutions were administered following an event-related design. We observed a statistically significant blood oxygen level-dependent (BOLD) response in the anatomically predicted location of the NTS for all five basic tastes. The results of this study appear statistically robust, even though they were obtained from a single volunteer. The information derived from a similar experimental strategy may inspire novel research aimed at clarifying important details of central nervous system involvement in eating disorders, at designing and monitoring tailored therapeutic strategies.

Liver fat in obesity: role of type 2 diabetes mellitus and adipose tissue distribution.

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 (1) H-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 < 0·001). DO had more liver fat (11·9 ± 7·0%) than NDO (5·2 ± 2·8%, P < 0·05) and C (1·6 ± 1·0%, P < 0·001). Abdominal fat was greater in DO and NDO than in C (visceral: DO 3184 ± 843, NDO 2843 ± 1378 vs. C 1212 ± 587 cm(3), P < 0·001; subcutaneous: DO 4029 ± 362, NDO 5197 ± 1398 vs. C 2312 ± 626 cm(3), P < 0·001), visceral fat being not significantly different between the two obese groups, and subcutaneous fat significantly less in DO than in NDO (P < 0·05). CONCLUSIONS: Type 2 diabetes is associated with increased fat accumulation in the liver, independent of obesity and whole-body insulin resistance. The increased liver fat in DO patients may be part of an altered regional fat distribution that includes an inadequate subcutaneous fat storing capacity, rather than simply being a consequence of increased abdominal visceral content.

Investigating the Relationship between White Matter Connectivity and Motivational Circuits in Subjects with Deficit Schizophrenia: A Diffusion Tensor Imaging (DTI) Study.

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.

Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy.

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 microg (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.

Cortical thickness, local gyrification index and fractal dimensionality in people with acute and recovered Anorexia Nervosa and in people with Bulimia Nervosa.

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.

Biofeedback Rehabilitation and Visual Cortex Response in Stargardt's Disease: A Randomized Controlled Trial.

Purpose: to evaluate the effect of biofeedback (BF) rehabilitation on the visual function and on the activity of primary visual cortex (PVC) in patients with Stargardt's disease owing to mutations in the ABCA4 gene (STGD1). Methods: This was a single-center, controlled, randomized study. Twenty-four patients with STGD1 were randomized into two groups: a treatment group (TG) undergoing BF rehabilitation and a control group (CG). Treatment with BF consisted of a 10-minute session per eye performed weekly for 12 weeks. The subjects underwent a baseline and 3-month follow-up visits, including best-corrected visual acuity (BCVA), reading test, microperimetry, and functional magnetic resonance imaging (fMRI). The fMRI studies were acquired sequentially using a passive viewing condition and an active reading task. The primary outcomes were the change in the fMRI activation of primary visual cortex and the change in reading ability. Results: After treatment, the patients in the TG were able to read smaller characters (P = 0.002) with a greater reading speed (P = 0.014) compared with patients in the CG. The fMRI studies showed a significant effect (P < 0.001) of BF on primary visual cortex activation in the TG compared with the CG. Finally, we observed significant (P < 0.05) improvements of best-corrected visual acuity, macular sensitivity, and fixation stability parameters in the TG compared with the CG. Conclusions: Our study showed that visual rehabilitation using BF improved the usage of residual visual function in patients with STGD1. Translational Relevance: Our findings show that the BF treatment compared with no treatment at all resulted in benefits. The specificity of the treatment could be examined to determine whether BF can be included in clinical practice.

Voxel-based analysis of gray matter relaxation rates shows different correlation patterns for cognitive impairment and physical disability in relapsing-remitting multiple sclerosis.

BACKGROUND: Regional analyses of markers of microstructural gray matter (GM) changes, including relaxation rates, have shown inconsistent correlations with physical and cognitive impairment in MS. OBJECTIVE: To assess voxelwise the correlation of the R1 and R2 relaxation rates with the physical and cognitive impairment in MS. METHODS: GM R1 and R2 relaxation rate maps were obtained in 241 relapsing-remitting MS patients by relaxometric segmentation of MRI studies. Correlations with the Expanded Disability Status Scale (EDSS) and the percentage of impaired cognitive test (Brief Repeatable Battery and Stroop Test, available in 186 patients) were assessed voxelwise, including voxel GM content as nuisance covariate to remove the effect of atrophy on the correlations. RESULTS: Extensive clusters of inverse correlation between EDSS and R2 were detected throughout the brain, while inverse correlations with R1 were mostly limited to perirolandic and supramarginal cortices. Cognitive impairment correlated negatively with R1, and to a lesser extent with R2, in the middle frontal, mesial temporal, midcingulate and medial parieto-occipital cortices. CONCLUSION: In relapsing-remitting MS patients, GM microstructural changes correlate diffusely with physical disability, independent of atrophy, with a preferential role of the sensorimotor cortices. Neuronal damage in the limbic system and dorsolateral prefrontal cortices correlates with cognitive dysfunction.

The effects of childhood maltreatment on brain structure in adults with eating disorders.

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.

A low-cost open-architecture taste delivery system for gustatory fMRI and BCI experiments.

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.

Brain tissue volumes and relaxation rates in multiple sclerosis: implications for cognitive impairment.

OBJECTIVE: 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. METHODS: 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). RESULTS: The R1 relaxation rate (a putative marker of tissue disruption) of the MS lesions appeared the single most significant contributor to cognitive impairment (p < 0.001). On the contrary, the EDSS appeared mainly affected by the decrease in R2 of the gray matter (p < 0.0001), (possibly influenced by cortical plaques, edema and inflammation). CONCLUSIONS: In RR-MS the tissue damage in white matter lesions appears the single main determinant of the cognitive status of patients, likely through disconnection phenomena, while the physical disability appears related to the involvement of gray matter.

Rehabilitation of gesture imitation: a case study with fMRI.

Acquired disorders of gesture imitation are amenable to treatment, but with poor generalisation toward gestures not included in the training program. We investigated the neural basis of this item-specific recovery in a patient with a slowly progressive posterior cortical atrophy, by means of an fMRI study comparing imitation of rehabilitated and not-rehabilitated gestures. Results suggested that in our patient gesture imitation recruited the mirror system and additional areas relevant to gesture analysis and preparation. Imitation of rehabilitated gestures activated the mirror neuron system, and also left dorsolateral prefrontal cortex and putamen, and the right anterior temporal cortex. This suggests that item-specific recovery was based on interaction of circuitry of imitation with neural systems involved in emotional and motivational processing.

Functional connectivity of the ventral tegmental area and avolition in subjects with schizophrenia: a resting state functional MRI study.

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".