68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine well-differentiated tumours.

PURPOSE: To explore the role of fully hybrid 68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine tumours (PanNETs) undergoing surgery. METHODS: One hundred eighty-seven consecutive 68Ga-DOTATOC PET/MRI scans (March 2018-June 2020) performed for gastroenteropancreatic neuroendocrine tumour were retrospectively evaluated; 16/187 patients met the eligibility criteria (68Ga-DOTATOC PET/MRI for preoperative staging of PanNET and availability of histological data). PET/MR scans were qualitatively and quantitatively interpreted, and the following imaging parameters were derived: PET-derived SUVmax, SUVmean, somatostatin receptor density (SRD), total lesion somatostatin receptor density (TLSRD), and MRI-derived apparent diffusion coefficient (ADC), arterial and late enhancement, necrosis, cystic degeneration, and maximum diameter. Additionally, first-, second-, and higher-order radiomic parameters were extracted from both PET and MRI scans. Correlations with several PanNETs' histopathological prognostic factors were evaluated using Spearman's coefficient, while the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate parameters' predictive performance. RESULTS: Primary tumour was detected in all 16 patients (15/16 by 68Ga-DOTATOC PET and 16/16 by MRI). SUVmax and SUVmean resulted good predictors of lymphnodal (LN) involvement (AUC of 0.850 and 0.783, respectively). Second-order radiomic parameters GrayLevelVariance and HighGrayLevelZoneEmphasis extracted from T2 MRI demonstrated significant correlations with LN involvement (adjusted p = 0.009), also showing good predictive performance (AUC = 0.992). CONCLUSION: This study demonstrates the role of the fully hybrid PET/MRI tool for the synergic function of imaging parameters extracted by the two modalities and highlights the potentiality of imaging and radiomic parameters in assessing histopathological features of PanNET aggressiveness.

Radiomics in pancreatic neuroendocrine tumors: methodological issues and clinical significance.

PURPOSE: To present the state-of-art of radiomics in the context of pancreatic neuroendocrine tumors (PanNETs), with a focus on the methodological and technical approaches used, to support the search of guidelines for optimal applications. Furthermore, an up-to-date overview of the current clinical applications of radiomics in the field of PanNETs is provided. METHODS: Original articles were searched on PubMed and Science Direct with specific keywords. Evaluations of the selected studies have been focused mainly on (i) the general radiomic workflow and the assessment of radiomic features robustness/reproducibility, as well as on the major clinical applications and investigations accomplished so far with radiomics in the field of PanNETs: (ii) grade prediction, (iii) differential diagnosis from other neoplasms, (iv) assessment of tumor behavior and aggressiveness, and (v) treatment response prediction. RESULTS: Thirty-one articles involving PanNETs radiomic-related objectives were selected. In regard to the grade differentiation task, yielded AUCs are currently in the range of 0.7-0.9. For differential diagnosis, the majority of studies are still focused on the preliminary identification of discriminative radiomic features. Limited information is known on the prediction of tumors aggressiveness and of treatment response. CONCLUSIONS: Radiomics is recently expanding in the setting of PanNETs. From the analysis of the published data, it is emerging how, prior to clinical application, further validations are necessary and methodological implementations require optimization. Nevertheless, this new discipline might have the potential in assisting the current urgent need of improving the management strategies in PanNETs patients.

Method for the estimation of a double hinge kinematic model for the trapeziometacarpal joint using MR imaging.

In this paper, we propose a method to estimate the parameters of a double hinge model of the trapeziometacarpal joint (TMC) by MRI-based motion analysis. The model includes two non-orthogonal and non-intersecting rotation axes accounting for flexion-extension (F-E) and adduction-abduction (A-A). We evaluated the quality of the estimated model parameters in the prediction of the relative motion of the first metacarpal bone with respect to the trapezium. As a result, we obtained that: (a) the estimated location and orientation of the F-E and A-A axes were in agreement with previous in vitro studies, (b) the motion of the first metacarpal predicted by the 2 degrees of freedom (2DoF) model exhibits a maximum surface distance error in the range of about 2 mm and (c) four thumb postures at the boundary of the TMC range of motion are sufficient to provide a good estimation of the 2DoF TMC kinematic model and good reproducibility (~1.7 mm) of the real thumb motion at TMC level.

Disorganization of anatomical connectivity in obsessive compulsive disorder: a multi-parameter diffusion tensor imaging study in a subpopulation of patients.

Obsessive-compulsive disorder (OCD) is thought to involve large-scale brain systems but the anatomical connectivity via association fibers has not been specifically investigated yet. We evaluated organization and directionality of the major fiber bundles in a subpopulation of OCD, including washers and checkers who presented decision making deficits, by measuring MRI parameters related to water self-diffusion (Fractional Anisotropy, FA) and fiber directionality (Principal Diffusion Direction, PDD) in 15 OCD and 16 control subjects. OCD patients showed significantly lower FA and altered PDD along the corpus callosum, cingulum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus bilaterally. The track-based analysis of the inferior fronto-occipital fasciculus confirmed a significant bilateral FA reduction. Lower FA values in the inferior fronto-occipital fasciculus, superior longitudinal fasciculus and corpus callosum correlated with symptom severity and neuropsychological performance. This multi-parameter MRI study revealed specific white matter abnormalities in OCD suggesting tract disorganization as main feature, reflected by local changes in fiber directionality. This altered anatomical connectivity might play a specific role in OCD pathophysiology.

Elevated fasting plasma C-peptide occurs in non-diabetic individuals with fatty liver, irrespective of insulin resistance.

AIMS: Studies have pointed to insulin resistance as a pathogenic factor in fatty liver. Although pancreatic B-cell function is believed to be involved, its role is unclear. This study was undertaken to test whether fasting C-peptide, an index of fasting B-cell function, was related to intra-hepatic fat (IHF) content in non-diabetic humans. METHODS: We assessed, retrospectively, fasting plasma C-peptide concentration in 31 patients with fatty liver and 62 individuals without fatty liver. The IHF content was measured by proton magnetic resonance spectroscopy ((1)H-MRS), while insulin sensitivity was estimated based on fasting plasma glucose and insulin with the homestasis model assessment (HOMA) 2 method. RESULTS: Age, sex and body mass index (BMI) were not different between groups. Patients with fatty liver had higher fasting insulin (P < 0.01), C-peptide (P < 0.005) and lower insulin sensitivity (HOMA2-%S). Fasting insulin alone explained 14% of the IHF content variability (P < 0.001); inclusion of fasting C-peptide in multivariate regression explained up to 32% (P < 0.001). A subgroup analysis was performed by matching 1 : 1 for HOMA2-%S. These data were analysed by conditional logistic regression which showed that, when HOMA2-%S was matched between groups, fasting C-peptide remained the only significant predictor of fatty liver. CONCLUSIONS: Non-diabetic individuals with fatty liver are characterized by increased fasting plasma C-peptide concentration, irrespective of their insulin resistant state.

Effect of L-acetylcarnitine on body composition in HIV-related lipodystrophy.

This study examined the impact of L-acetylcarnitine treatment on metabolic parameters and body composition in patients with lipodystrophy syndrome secondary to antiretroviral treatment in human immunodeficiency virus (HIV) infection. A total of 9 HIV-1 infected patients with lipodystrophy syndrome (4F/5M, age 41+/-5 years, HIV duration 8+/-2 years, BMI 23.7+/-3.4 kg/m(2), on protease inhibitors and nucleoside analogue Reverse Transcriptase inhibitors) were evaluated before and after 8 months of therapy with L-acetylcarnitine (2 g/die) and 9 matched healthy subjects served as control subjects. In all patients fasting plasma glucose, insulin concentrations (for evaluation of surrogate indexes of insulin sensitivity), lipid profile, lipid oxidation (by indirect calorimetry), body composition (by DEXA), and intramyocellular triglyceride (IMCL) content of the calf muscles (by (1)H NMR spectroscopy) were assessed. After this therapy, in HIV-1 patients, the IMCL content of the soleus had significantly decreased (p=0.03). Plasma FFAs (0.79+/-0.31 to 0.64+/-0.25; p<0.05) and Respiratory Quotient (0.83+/-0.18 to 0.72+/-0.16; p<0.03) also decreased. Insulin sensitivity was significantly lower prior (HOMA-IS 0.56+/-0.30) and nonstatistically different than controls after therapy (0.72+/-0.49 vs. 0.78+/-0.42) whilst the percentage of fat in the legs increased (p=0.05). Eight months of L-acetylcarnitine treatment increased lipid oxidation, decreased intramyocellular triglyceride content, and induced a more physiological distribution of fat deposits.

Left ventricular function and energy metabolism in middle-aged men undergoing long-lasting sustained aerobic oxidative training.

OBJECTIVE: Ageing of the human heart is characterised by morphological, functional and metabolic changes. Short-term interventions and cross-sectional studies in older individuals questioned the possibility that physical exercise may reverse these alterations. In this study we aimed to assess whether in middle-aged men involved in regular and long lasting physical activity these alterations were attenuated. DESIGN: Left ventricular (LV) magnetic resonance imaging (MRI) and three-dimensional image selected in-vivo spectroscopy (3D-ISIS) (31)P magnetic resonance spectroscopy (MRS) were performed using a 1.5T scanner in 20 healthy, young and 25 healthy middle-aged non-obese men with a sedentary lifestyle (11 young and 14 middle-aged) or undergoing regular aerobic oxidative training (9 young and 11 middle-aged). Insulin sensitivity was estimated by the homeostatic model assessment 2 (HOMA-2) model. RESULTS: Sedentary young and middle-aged men were not different with respect to LV morphological parameters and systolic function. The phosphocreatine/ATP (PCr/ATP) ratio (marker of high energy phosphates metabolism) and the LV E-peak filling rate/A-peak filling rate ratio (E/A ratio) were lower in sedentary middle-aged than physically active subjects. Parameters of LV systolic function and the PCr/ATP ratio were not different in the middle-aged compared with the young trained men; the E/A peak flow ratio was higher in the middle-aged trained men than in the middle-aged sedentary men. Within the entire population, the PCr/ATP ratio and the E/A peak flow ratio were associated with insulin sensitivity. CONCLUSIONS: Trained middle-aged subjects showed a better pattern of LV energy metabolism and of diastolic function than their sedentary counterparts. At this age the exercise-related cardiac benefits were detectable when physical exercise was performed regularly and for a long period of time.

Impaired left ventricular energy metabolism in patients with hypertrophic cardiomyopathy is related to the extension of fibrosis at delayed gadolinium-enhanced magnetic resonance imaging.

OBJECTIVE: Areas of intramyocardial late enhancement (LE) at delayed enhanced magnetic resonance imaging (DE-MRI) and reduction of myocardial phosphocreatine (PCr)/ATP-ratio at phosphorus magnetic resonance spectroscopy ((31)P-MRS) are both reported in hypertrophic cardiomyopathy (HCM) and indicate areas of increased interstitial myocardial space with fibrosis and impairment of myocardial energy metabolism, respectively. We sought to ascertain whether in HCM patients the abnormal features of left ventricular (LV) interstitial space revealed by DE-MRI correlated with impaired LV energy metabolism shown at (31)P-MRS. METHODS: 19 patients with HCM proved by histological analysis of multiple endomyocardial biopsies and with normal coronary arteries, underwent cardiac MRI including DE-MRI and (31)P-MRS. DE-MRI for detection and quantification of late enhancement (LE) and (31)P-MRS to assess the myocardial PCr/ATP-ratio were performed by means of a 1.5-T magnet. 19 healthy subjects, matched for gender and age were studied by (31)P-MRS as control group. RESULTS: LE areas in the LV wall were found in 17 out of 19 patients with an extension ranging from 0.8% to 19.5% of the LV-mass (mean value 7.6% (SD 5.6%). The PCr/ATP-ratio was lower in HCM patients than in control subjects (2.18 (0.41) vs 2.41 (0.30); p<0.05). LE% and PCr/ATP-ratio were inversely related (R = -0.57; p<0.05) and LE% was the stronger predictor of PCr/ATP-ratio by multivariate analysis. CONCLUSIONS: This study demonstrated that the known alteration of the PCr/ATP-ratio observed in HCM patients is correlated with the presence of fibrotic areas in the myocardium of the left ventricle.

Hippocampal infolding angle changes during brain development assessed by prenatal MR imaging.

BACKGROUND AND PURPOSE: Epileptic syndromes or neurodevelopmental delay may be associated with congenital anomalies of the shape or the orientation of the hippocampus. Scarce data are available about quantitative hippocampal developmental changes during fetal life, in particular about the progressive rotational changes of the hippocampal infolding angle (HIA), which can be considered a hallmark of hippocampal development. We hypothesized that prenatal MR imaging could demonstrate the progressive rotation of the hippocampus, providing quantitative data by means of the HIA determination. METHODS: We retrospectively selected 62 fetal MR imaging cases with normal brain at prenatal and postnatal imaging. The gestational age ranged from 20 to 37 weeks. The coronal section encompassing the pons was used to perform the measurement of HIA. HIA was defined as the angle between the line connecting the lateral margin of the cornu ammonis with the medial superior margin of the subiculum and the line passing through the midline structures. RESULTS: A significant positive correlation was found between the HIA value and the gestational age. The HIA was generally below 70 degrees before the gestational week 25 and above 70 degrees after week 30. CONCLUSION: Prenatal MR imaging allowed the progressive rotation of hippocampus to be detected during fetal life, providing normative data about HIA changes. These data could support further investigations to assess how fetal HIA anomalies might affect postnatal neurologic outcome.

Diffusion tensor imaging and voxel based morphometry study in early progressive supranuclear palsy.

BACKGROUND: A comprehensive characterisation of grey and white matter changes in progressive supranuclear palsy (PSP), the second most common extrapyramidal syndrome after Parkinson disease, is still not available. OBJECTIVE: To evaluate grey and white matter changes in mild PSP patients by voxel based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. METHODS: 14 mild PSP patients and 14 healthy controls entered the study and underwent a clinical and neuropsychological evaluation according with a standardised assessment. Each subject had a structural magnetic resonance imaging (MRI) study. Processing analysis of MRI data was carried out according to optimised VBM and fractional anisotropy was determined. RESULTS: Compared with the controls, in PSP patients VBM analysis showed a significant clusters of reduced grey matter in premotor cortex, frontal operculum, anterior insula, hippocampus, and parahippocampal gyrus, bilaterally. With regard to subcortical brain regions, the pulvinar, dorsomedial and anterior nuclei of the thalamus, and superior and inferior culliculum were affected bilaterally. A bilateral decrease in fractional anisotropy in superior longitudinal fasciculus, anterior part of corpus callosum, arcuate fascicolus, posterior thalamic radiations, and internal capsule, probably involving the cortico-bulbar tracts, was present in PSP patients. CONCLUSIONS: These data provide evidence for both grey and white matter degeneration in PSP from the early disease stage. These structural changes suggest that atrophy of cortical and subcortical structures and neurodegeneration of specific fibre tracts contribute to neurological deficits in PSP.

Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes.

AIMS/HYPOTHESIS: Insulin resistance may be associated with ectopic fat accumulation potentially determined by reduced lipid oxidation. In patients with type 1 diabetes peripheral insulin resistance is associated with higher intramyocellular lipid content. We assessed whether these patients are also characterised by intrahepatic fat accumulation and abnormal fat oxidation. METHODS: Nineteen patients with type 1 diabetes (6 women, 13 men, age 35+/-7 years, BMI 23+/-3 kg/m2), HbA1c 8.7+/-1.4%) and 19 healthy matched individuals were studied by (1) euglycaemic-hyperinsulinaemic clamp combined with [6,6-2H2]glucose infusion to assess whole-body glucose metabolism; (2) indirect calorimetry to assess glucose and lipid oxidation; and (3) localised 1H-magnetic resonance spectroscopy of the liver to assess intrahepatic fat content. RESULTS: Patients with type 1 diabetes showed a reduced insulin-stimulated metabolic clearance rate of glucose (4.3+/-1.3 ml kg(-1) min(-1)) in comparison with normal subjects (6.0+/-1.6 ml kg(-1) min(-1); p<0.001). Endogenous glucose production was higher in diabetic patients (p=0.001) and its suppression was impaired during insulin administration (66+/-30 vs 92+/-8%; p=0.047) in comparison with normal subjects. Plasma glucagon concentrations were not different between groups. The estimated hepatic insulin concentration was lower in diabetic patients than in normal subjects (p<0.05), as was the intrahepatic fat content (1.5+/-0.7% and 2.2+/-1.0% respectively; p<0.03), the latter in association with a reduced respiratory quotient (0.74+/-0.05 vs 0.84+/-0.06; p=0.01) and increased fasting lipid oxidation (1.5+/-0.5 vs 0.8+/-0.4 mg kg(-1) min(-1); p<0.01). CONCLUSIONS/INTERPRETATION: In patients with type 1 diabetes, insulin resistance was not associated with increased intrahepatic fat accumulation. In fact, diabetic patients had reduced intrahepatic fat content, which was associated with increased fasting lipid oxidation. The unbalanced hepatic glucagon and insulin concentrations affecting patients with type 1 diabetes may be involved in this abnormality of intrahepatic lipid metabolism.

Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients.

AIMS/HYPOTHESIS: Intramyocellular lipid accumulation and insulin resistance are thought to be due to reduced lipid oxidation in a human model of high risk of developing type 2 diabetes. METHODS: We studied 32 offspring of type 2 diabetic parents and 32 control individuals by means of DXA, indirect calorimetry, insulin clamp and 1H MRS of the calf muscles, and differences between and within study groups were analysed before and after segregation by quartiles of fasting lipid oxidation. RESULTS: In comparison with control subjects, the offspring showed impaired insulin sensitivity, which was associated with higher fasting intramyocellular lipid content (Spearman's rho -0.35; p=0.04), but fasting lipid oxidation did not differ between groups (1.21+/-0.46 vs. 1.25+/-0.37 mg.kg(-1) lean body mass per min; p=0.70). Nevertheless, offspring in the lowest quartile of lipid oxidation had the most severe impairment of insulin sensitivity and a strong association was shown between lipid oxidation and insulin sensitivity within quartiles (Spearman's rho 0.47; p=0.01); this was not observed within the control group (Spearman's rho 0.13; p=0.47). Intramyocellular lipid content was not significantly different within quartiles of lipid oxidation in either of the groups. CONCLUSIONS/INTERPRETATION: Insulin sensitivity improved across increasing quartiles of fasting lipid oxidation in the offspring group, but remained constant in the control group, supporting the hypothesis that impaired fat oxidation is a primary pathogenic factor of insulin resistance in people with a genetic background for type 2 diabetes. Despite their association with impaired insulin sensitivity, soleus and tibialis anterior intramyocellular lipid content remained constant across increasing quartiles of fasting lipid oxidation within both groups.

A Deconvolution Approach Based on Multi-Tensor Model to Solve Fiber Crossing in Diffusion-MRI.

A deconvolution approach, based on a multi-tensor model, is presented to solve fiber crossing in diffusion MRI. In order to provide a direct physical interpretation of the signal generation process, we re-wrote the classical multi-tensor model, identifying a significant scalar parameter alpha to characterize the deconvolution process. Simulations show that, in presence of noise, the method is able to correctly separate fiber crossing. Application on in-vivo data highlights the ability of our approach to distinguish more than two fibers within the same voxel, suggesting its application in fiber tracking or connectivity studies even of complex brain structures.

A framework to study the cortical folding patterns.

This paper describes a decade-long research program focused on the variability of the cortical folding patterns. The program has developed a framework of using artificial neuroanatomists that are trained to identify sulci from a database. The framework relies on a renormalization of the brain warping problem, which consists in matching the cortices at the scale of the folds. Another component of the program is the search for the alphabet of the folding patterns, namely, a list of indivisible elementary sulci. The search relies on the study of the cortical folding process using antenatal imaging and on backward simulations of morphogenesis aimed at revealing traces of the embryologic dimples in the mature cortical surface. The importance of sulcal-based morphometry is illustrated by a simple study of the correlates of handedness on asymmetry indices. The study shows for instance that the central sulcus is larger in the dominant hemisphere.

Preserved functional competence of perilesional areas in drug-resistant epilepsy with lesion in supplementary motor cortex: fMRI and neuropsychological observations.

We report a presurgical fMRI study and a longitudinal behavioral and structural MRI study in a 26-year-old right-handed woman with drug-resistant epilepsy of the supplementary motor region with cytoarchitectural dysplasia and minimal cortico-subcortical gliotic damage. fMRI scans were acquired during a silent phonemic verbal fluency task (VF), an automatic counting task (CT), and a finger-tapping motor task (MT). These were all compared with rest. Presurgical neuropsychological assessment was substantially normal with only a minor deficit in the domain of visuo-constructive and complex motor-planning skills. Noticeably, performance on phonemic verbal fluency was normal. Presurgical fMRI results revealed a normal specialization of left SMA and pre-SMA, including a fine-grained somatotopy for mouth and hand representations despite epilepsy. Immediately after surgical removal of the epileptogenic zone (the posterior third of the superior and middle frontal gyri including pre-SMA and part of SMA, and part of the anterior cingulate region--all of which were active presurgically at the fMRI tests), the patient suffered from transcortical motor aphasia temporarily. One year after surgery, she still showed impaired performance in the verbal fluency tasks while naming and comprehension were recovered. The patient was now free from seizures. This fMRI study supports the case that repeated seizures per se may not be sufficient to alter the distribution of neural representations of cognitive function. Selective behavioral impairment after surgical removal of brain areas that were activated during presurgical fMRI permits us to establish a causal link between these activations and task performance. This link could not have been made on the basis of activation patterns or lesion data taken on their own. These findings support the case that some epileptic patients may represent a unique opportunity for cognitive neuroscience studies.

Apomorphine-induced brain modulation during sexual stimulation: a new look at central phenomena related to erectile dysfunction.

It is well recognized that sexual stimulation leading to penile erection is controlled by different areas in the brain. Animal erection studies have shown that apomorphine (a D2>D1 dopamine receptors nonselective agonist) seems to act on neurons located within the paraventricular nucleus and the medial preoptic area of the hypothalamus. Yet, only recently, was a centrally acting agent, apomorphine sublingual, approved for the treatment of erectile dysfunction. The present functional magnetic resonance imaging placebo-controlled study presents the first in vivo demonstration of the apomorphine-induced modulation of cortical and subcortical brain structures in patients with psychogenic erectile dysfunction. Noteworthy, patients in comparison with potent controls, showed an increased activity in frontal limbic areas that was downregulated by apomorphine. This suggests that psychogenic impotence may be associated with previously unrecognized underlying functional abnormalities of the brain.

A fMRI study of word retrieval in aphasia.

The neural mechanisms underlying recovery of cognitive functions are incompletely understood. Aim of this study was to assess, using functional magnetic resonance (fMRI), the pattern of brain activity during covert word retrieval to letter and semantic cues in five aphasic patients after stroke, in order to assess the modifications of brain function which may be related to recovery. Four out of five patients had undergone language recovery, according to standard testing, after at least 6 months of rehabilitation. The cerebral activation of each patient was evaluated and compared with the activation pattern of normal controls studied with the same fMRI paradigm. In the patients, the pattern of brain activation was influenced by the site and extent of the lesion, by the degree of recovery of language, as reflected by task performance outside the scanner, and by task requirements. In the case of word retrieval to letter cues, a good performance was directly related to the activation in Broca's area, or in the right-sided homologue. On the other hand, in the case of semantic fluency, the relationship between performance level and activation was less clear-cut, because of extensive recruitment of frontal areas in patients with defective performance. These findings suggest that the performance in letter fluency is dependent on the integrity of the left inferior frontal cortex, with the participation of the homologous right hemispheric region when the left inferior frontal cortex is entirely of partially damaged. Semantic fluency, which engages the distributed network of semantic memory, is also associated with more extensive patterns of cerebral activation, which however appear to reflect retrieval effort rather than retrieval success.

Interhemispheric transmission of visuomotor information in humans: fMRI evidence.

Normal human subjects underwent functional magnetic resonance imaging (fMRI) while performing a simple visual manual reaction-time (RT) task with lateralized brief stimuli, the so-called Poffenberger's paradigm. This paradigm was employed to measure interhemispheric transmission (IT) time by subtracting mean RT for the uncrossed hemifield-hand conditions, that is, those conditions not requiring an IT, from the crossed hemifield-hand conditions, that is, those conditions requiring an IT to relay visual information from the hemisphere of entry to the hemisphere subserving the response. The obtained difference is widely believed to reflect callosal conduction time, but so far there is no direct physiological evidence in humans. The aim of our experiment was twofold: first, to test the hypothesis that IT of visuomotor information requires the corpus callosum and to identify the cortical areas specifically activated during IT. Second, we sought to discover whether IT occurs mainly at premotor or perceptual stages of information processing. We found significant activations in a number of frontal, parietal, and temporal cortical areas and in the genu of the corpus callosum. These activations were present only in the crossed conditions and therefore were specifically related to IT. No selective activation was present in the uncrossed conditions. The location of the activated callosal and cortical areas suggests that IT occurs mainly, but not exclusively, at premotor level. These results provide clear cut evidence in favor of the hypothesis that the crossed-uncrossed difference in the Poffenberger paradigm depends on IT rather than on a differential hemispheric activation.

Gender factors affect fatty acids-induced insulin resistance in nonobese humans: effects of oral steroidal contraception.

Plasma free fatty acids and intramyocellular triglycerides (IMCL) content modulate whole body insulin sensitivity in humans. To test whether the interactions between fatty acid metabolism and insulin action in nonobese humans are related to gender factors, we studied 15 young, normal weight, healthy men and 15 women matched for life habits and whole body insulin sensitivity, determined with the euglycemic-hyperinsulinemic clamp, by means of indirect calorimetry to assess substrate oxidation, localized (1)H nuclear magnetic resonance spectroscopy of calf muscles to assess IMCL content, and dual energy x-ray absorption to assess body composition. In addition, to test whether perturbation of the feminine hormonal milieu modifies these interactions, we studied 15 matched females using oral steroidal contraception (OSC). Insulin sensitivity in women, notwithstanding increased body fatness, plasma free fatty acids, IMCL content, and circulating beta-hydroxybutyrate levels and reduced lipid oxidation, was similar to that in men. Women using OSC showed a 40% reduction of insulin sensitivity associated with increased plasma free fatty acids, beta-hydroxybutyrate, cholesterol, and triglycerides levels and a slight increment in IMCL content compared with women with intact hormonal cycles. In all groups the IMCL content was inversely related to insulin sensitivity. In conclusion, nonobese, healthy, young women are as insulin sensitive as men, notwithstanding the higher levels of postabsorptive circulating and tissue-stored fatty acids; OSC-induced insulin resistance is associated with abnormal fatty acid metabolism and loss of this gender-related feature.

Remodelling of sensorimotor maps in paraplegia: a functional magnetic resonance imaging study after a surgical nerve transfer.

The adult mammalian brain has the capacity of reorganising its neural connections in response to lesions/modifications of the peripheral and central nervous system. We show in vivo, using functional magnetic resonance imaging (fMRI), that in paraplegics the lower-limb sensorimotor cortex is invaded by the arm representation. This functional reshaping appears to be reversible. Indeed, surgical transfer of the ulnar nerve to the ipsilateral quadriceps and hip muscles allowed their contraction in a paraplegic patient. During fMRI, these voluntary movements activated the hip and thigh representation in sensorimotor cortex. We suggest that the functional recovery of the lower-limb functional maps might have been driven by the restored somatosensory inputs from the reactivated periphery. The voluntary movements of the lower-limbs are regained through the 're-awakening' of the corresponding sensorimotor cortex.