Biomedical subjects

Tommaso Scarabino

Publications and source records attributed to Tommaso Scarabino.

At least 19 recordsLinked to original sources

PubMed2006

Preferential responses in amygdala and insula during presentation of facial contempt and disgust.

Some authors consider contempt to be a basic emotion while others consider it a variant of disgust. The neural correlates of contempt have not so far been specifically contrasted with disgust. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks involved in the processing of facial contempt and disgust in 24 healthy subjects. Facial recognition of contempt was lower than that of disgust and of neutral faces. The imaging data indicated significant activity in the amygdala and in globus pallidus and putamen during processing of contemptuous faces. Bilateral insula and caudate nuclei and left as well as right inferior frontal gyrus were engaged during processing of disgusted faces. Moreover, direct comparisons of contempt vs. disgust yielded significantly different activations in the amygdala. On the other hand, disgusted faces elicited greater activation than contemptuous faces in the right insula and caudate. Our findings suggest preferential involvement of different neural substrates in the processing of facial emotional expressions of contempt and disgust.

Adult↗

PubMed2006

Prefrontal dysfunction in schizophrenia controlling for COMT Val158Met genotype and working memory performance.

Earlier studies with functional imaging in schizophrenia have demonstrated dysfunction of the dorsolateral prefrontal cortex during working memory. Controlling for behavioral performance and for catechol-O-methyltransferase (COMT) Val158Met genotype, we here demonstrate in a functional magnetic resonance imaging paradigm that patients recruit greater neuronal resources in prefrontal cortex during working memory, suggesting that this phenotype is a core functional trait of the disease. We also replicated earlier findings that the Val allele of the COMT polymorphism is associated with greater engagement of the prefrontal cortex.

Adult↗

PubMed2006

Prefrontal-hippocampal coupling during memory processing is modulated by COMT val158met genotype.

BACKGROUND: Studies in humans and in animals have demonstrated that a network of brain regions is involved in performance of declarative and recognition memory tasks. This network includes the hippocampal formation (HF) as well as the ventrolateral prefrontal cortex (VLPFC). Studies in animals have suggested that the relationship between these brain regions is strongly modulated by dopamine. METHODS: Using fMRI in healthy humans matched for a series of demographic and genetic variables, we studied the effect of the COMT val158met polymorphism on function of HF and VLPFC as well as on their functional coupling during recognition memory. RESULTS: The COMT Val allele was associated with: relatively poorer performance at retrieval; reduced recruitment of neuronal resources in HF and increased recruitment in VLPFC during both encoding and retrieval; and unfavorable functional coupling between these two regions at retrieval. Moreover, functional coupling during retrieval was predictive of behavioral accuracy. CONCLUSIONS: These results shed new light on individual differences in responsivity and connectivity between HF and VLPFC related to genetic modulation of dopamine, a mechanism accounting at least in part for individual differences in recognition memory performance.

Adult↗

PubMed2006

Independent component model of the default-mode brain function: Assessing the impact of active thinking.

The "default-mode" network is an ensemble of cortical regions, which are typically deactivated during demanding cognitive tasks in functional magnetic resonance imaging (fMRI) studies. Using functional connectivity, this network can be conceptualized and studied as a "stand-alone" function or system. Regardless of the task, independent component analysis (ICA) produces a picture of the "default-mode" function even when the subject is performing a simple sensori-motor task or just resting in the scanner. This has boosted the use of default-mode fMRI for non-invasive research in brain disorders. Here, we studied the effect of cognitive load modulation of fMRI responses on the ICA-based pictures of the default-mode function. In a standard graded working memory study based on the n-back task, we used group-level ICA to explore the variability of the default-mode network related to the engagement in the task, in 10 healthy volunteers. The analysis of the default-mode components highlighted similarities and differences in the layout under three different cognitive loads. We found a load-related general increase of deactivation in the cortical network. Nonetheless, a variable recruitment of the cingulate regions was evident, with greater extension of the anterior and lesser extension of the posterior clusters when switching from lower to higher working memory loads. A co-activation of the hippocampus was only found under no working memory load. As a generalization of our results, the variability of the default-mode pattern may link the default-mode system as a whole to cognition and may more directly support use of the ICA model for evaluating cognitive decline in brain disorders.

Adult↗

PubMed2006

Supratentorial cerebral cavernous malformations: clinical, surgical, and genetic involvement.

OBJECT: Although there is general agreement on the methods of treatment for symptomatic supratentorial cerebral cavernous malformations (CMs) located in noneloquent areas, some controversy exists regarding the management of cerebral CMs that are asymptomatic and/or located in eloquent or deep areas. Moreover, recent advances in genetic findings could influence both standard clinical management and the follow-up strategy in affected individuals. Thus, the objective of this study was to develop, based on the authors' experience and a literature review, a management algorithm to deal with supratentorial cerebral CMs. METHODS: The authors retrospectively reviewed the clinical data related to 118 patients who underwent surgery for symptomatic supratentorial cerebral CMs at their institution. Twenty-eight of 118 patients harbored multiple lesions, and nine of these 28 patients had a clinically positive familial history. Genetic investigations were performed in 89 patients (75%). CONCLUSIONS: Surgery for supratentorial cerebral CMs in noneloquent locations is safe and curative. In cerebral CMs located in deep and eloquent areas and with symptoms including progressive neurological deficits, evidence of hemorrhage, and uncontrolled seizures, surgical treatment according to an integrated plan based on frameless stereotactic guidance and functional magnetic resonance imaging is recommended and results in acceptably low morbidity. The data support the need for long-term imaging follow up in all patients, careful preoperative vascular studies to detect associated venous anomalies, and the importance of genetic mutational analysis. The DNA screening protocol will change the care of family members of patients with familial forms of cerebral CMs, because affected asymptomatic family members may benefit by early detection of lesions. At the same time, the exclusion of family members who are not carriers of the mutation as members of the population at risk reduces the economic and psychological burden of clinical and instrumental monitoring.

Adolescent↗

PubMed2006

Multiparametric 3T MR approach to the assessment of cerebral gliomas: tumor extent and malignancy.

INTRODUCTION: Contrast-enhanced MR imaging is the method of choice for routine assessment of brain tumors, but it has limited sensitivity and specificity. We verified if the addition of metabolic, diffusion and hemodynamic information improved the definition of glioma extent and grade. METHODS: Thirty-one patients with cerebral gliomas (21 high- and 10 low-grade) underwent conventional MR imaging, proton MR spectroscopic imaging ((1)H-MRSI), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) at 3 Tesla, before undergoing surgery and histological confirmation. Normalized metabolite signals, including choline (Cho), N-acetylaspartate (NAA), creatine and lactate/lipids, were obtained by (1)H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. RESULTS: Perienhancing areas with abnormal MR signal showed 3 multiparametric patterns: "tumor", with abnormal Cho/NAA ratio, lower ADC and higher rCBV; "edema", with normal Cho/NAA ratio, higher ADC and lower rCBV; and "tumor/edema", with abnormal Cho/NAA ratio and intermediate ADC and rCBV. Perienhancing areas with normal MR signal showed 2 multiparametric patterns: "infiltrated", with high Cho and/or abnormal Cho/NAA ratio; and "normal", with normal spectra. Stepwise discriminant analysis showed that the better classification accuracy of perienhancing areas was achieved when regarding all MR variables, while (1)H-MRSI variables and rCBV better differentiated high- from low-grade gliomas. CONCLUSION: Multiparametric MR assessment of gliomas, based on (1)H-MRSI, PWI and DWI, discriminates infiltrating tumor from surrounding vasogenic edema or normal tissues, and high- from low-grade gliomas. This approach may provide useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Adolescent↗

PubMed2006

Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain.

Functional polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) genes modulate dopamine inactivation, which is crucial for determining neuronal signal-to-noise ratios in prefrontal cortex during working memory. We show that the COMT Met158 allele and the DAT 3' variable number of tandem repeat 10-repeat allele are independently associated in healthy humans with more focused neuronal activity (as measured with blood oxygen level-dependent functional magnetic resonance imaging) in the working memory cortical network, including the prefrontal cortex. Moreover, subjects homozygous for the COMT Met allele and the DAT 10-repeat allele have the most focused response, whereas the COMT Val and the DAT 9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory.

Adult↗

PubMed2006

How does spatial extent of fMRI datasets affect independent component analysis decomposition?

Spatial independent component analysis (sICA) of functional magnetic resonance imaging (fMRI) time series can generate meaningful activation maps and associated descriptive signals, which are useful to evaluate datasets of the entire brain or selected portions of it. Besides computational implications, variations in the input dataset combined with the multivariate nature of ICA may lead to different spatial or temporal readouts of brain activation phenomena. By reducing and increasing a volume of interest (VOI), we applied sICA to different datasets from real activation experiments with multislice acquisition and single or multiple sensory-motor task-induced blood oxygenation level-dependent (BOLD) signal sources with different spatial and temporal structure. Using receiver operating characteristics (ROC) methodology for accuracy evaluation and multiple regression analysis as benchmark, we compared sICA decompositions of reduced and increased VOI fMRI time-series containing auditory, motor and hemifield visual activation occurring separately or simultaneously in time. Both approaches yielded valid results; however, the results of the increased VOI approach were spatially more accurate compared to the results of the decreased VOI approach. This is consistent with the capability of sICA to take advantage of extended samples of statistical observations and suggests that sICA is more powerful with extended rather than reduced VOI datasets to delineate brain activity.

Acoustic Stimulation↗

PubMed2005

Gadolinium dose optimisation in patients with multiple sclerosis: intra- and inter-individual comparisons.

OBJECTIVE: To assess the efficacy of single, double and triple doses of 1M gadolinium in the magnetic resonance (MR) evaluation of multiple sclerosis (MS) lesions in order to establish the best trade-off in terms of dose and number of injections. MATERIALS AND METHODS: Twenty-three patients with relapsing remitting or secondary progressive MS underwent MR scans of the brain, spine or both. Signal intensity, the number of enhancing lesions and the areas of MS plaque were measured in T1-weighted images before and after single, double or triple doses of contrast medium. Wilcoxon's two-sample test and the Mann-Whitney U-test were used to evaluate the differences between the groups, and between doses in the same patient. RESULTS: There was no significant difference in area signal intensity or the number of enhancing lesions between the group examined after a single injection of double-dose (DD) contrast medium and the group examined after multiple injections of a triple dose (TD). The difference in the areas of enhancement and signal intensity between a single dose (SD) and TD significantly increased after the second bolus. CONCLUSION: Gadolinium injections in MS patients can be optimised by giving a single DD bolus, which leads to the same results as a TD administered as two boli.

Adult↗

PubMed2005

Variation of human amygdala response during threatening stimuli as a function of 5'HTTLPR genotype and personality style.

BACKGROUND: In the brain, processing of fearful stimuli engages the amygdala, and the variability of its activity is associated with genetic factors as well as with emotional salience. The objective of this study was to explore the relevance of personality style for variability of amygdala response. METHODS: We studied two groups (n=14 in each group) of healthy subjects categorized by contrasting cognitive styles with which they attribute salience to fearful stimuli: so-called phobic prone subjects who exaggerate potential environmental threat versus so-called eating disorders prone subjects who tend to be much less centered around fear. The two groups underwent functional magnetic resonance imaging (fMRI) at 3T during performance of a perceptual task of threatening stimuli and they were also matched for the genotype of the 5' variable number tandem repeat (VNTR) polymorphism in the serotonin transporter. RESULTS: The fMRI results indicated that phobic prone subjects selectively recruit the amygdala to a larger extent than eating disorders prone subjects. Activity in the amygdala was also independently predicted by personality style and genotype of the serotonin transporter. Moreover, brain activity during a working memory task did not differentiate the two groups. CONCLUSIONS: The results of the present study suggest that aspects of personality style are rooted in biological responses of the fear circuitry associated with processing of environmental information.

Adult↗

PubMed2005

Independent component analysis of fMRI group studies by self-organizing clustering.

Independent component analysis (ICA) is a valuable technique for the multivariate data-driven analysis of functional magnetic resonance imaging (fMRI) data sets. Applications of ICA have been developed mainly for single subject studies, although different solutions for group studies have been proposed. These approaches combine data sets from multiple subjects into a single aggregate data set before ICA estimation and, thus, require some additional assumptions about the separability across subjects of group independent components. Here, we exploit the application of similarity measures and a related visual tool to study the natural self-organizing clustering of many independent components from multiple individual data sets in the subject space. Our proposed framework flexibly enables multiple criteria for the generation of group independent components and their random-effects evaluation. We present real visual activation fMRI data from two experiments, with different spatiotemporal structures, and demonstrate the validity of this framework for a blind extraction and selection of meaningful activity and functional connectivity group patterns. Our approach is either alternative or complementary to the group ICA of aggregated data sets in that it exploits commonalities across multiple subject-specific patterns, while addressing as much as possible of the intersubject variability of the measured responses. This property is particularly of interest for a blind group and subgroup pattern extraction and selection.

Adult↗

PubMed2004

Functional lateralization of the sensorimotor cortex in patients with schizophrenia: effects of treatment with olanzapine.

BACKGROUND: Earlier cross-sectional studies with functional magnetic resonance imaging (fMRI) in treated patients with schizophrenia have reported abnormalities of cortical motor processing, including reduced lateralization of primary sensory motor cortex. The objective of the present longitudinal study was to evaluate whether such cortical abnormalities represent state or trait phenomena of the disorder. METHODS: Seventeen acutely ill, previously untreated patients were studied after 4 weeks and after 8 weeks of olanzapine therapy. Seventeen matched healthy subjects served as control subjects. All subjects underwent two fMRI scans 4 weeks apart during a visually paced motor task using a simple periodic block design. Functional magnetic resonance imaging data were analyzed in Statistical Parametric Mapping (SPM99). Region of interest analyses were used to determine a laterality quotient (an index of lateralization) of motor cortical regions. RESULTS: The fMRI data indicated that patients had reduced activation of the primary sensory motor cortex at 4 weeks but not at 8 weeks; however, the laterality quotient in the primary sensory motor cortex was reduced in patients at both time points. CONCLUSIONS: These results suggest that some cortical abnormalities during motor processing represent state phenomena, whereas reduced functional lateralization of the primary sensory motor cortex represents an enduring trait of schizophrenia.

Adolescent↗

PubMed2004

Hippocampal neurochemical pathology in patients at first episode of affective psychosis: a proton magnetic resonance spectroscopic imaging study.

While several studies have suggested a relationship between the hippocampus and psychosis in schizophrenia, fewer studies have specifically investigated the presence of psychosis in mood disorders from a neurobiological perspective. Moreover, a limitation of these earlier studies is that the majority of them were performed in chronic patients. The present proton magnetic resonance spectroscopic imaging (1H-MRSI) study assessed neuronal integrity (as assessed with N-acetylaspartate, NAA) in the hippocampus of patients with a first episode of mood disorders with psychotic symptoms. We studied 17 patients and 17 healthy subjects matched for age and sex. Subjects underwent 1H-MRSI, and measures of NAA, choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in 11 brain regions were obtained, i.e. hippocampus (HIPPO), dorsolateral prefrontal cortex, superior temporal gyrus, inferior frontal gyrus, occipital cortex, anterior and posterior cingulate, centrum semiovale, prefrontal white matter, thalamus and putamen. NAA/CRE ratios in HIPPO of patients were significantly lower than in controls. Sporadic and non-hypothesis-driven results were found in occipital cortex and prefrontal white matter as a main effect of diagnosis, and in superior temporal gyrus as a hemisphere by diagnosis interaction. These results would not survive a Bonferroni correction for the number of ROIs. No correlations were found with the available demographic and clinical data. Therefore, hippocampal neuronal abnormalities are present at the onset of mood disorders with psychotic symptoms. These data suggest that neuronal abnormalities in HIPPO may be associated with psychosis in mood disorders. Since these data were obtained in patients at first episode, they cannot be explained by chronicity of illness or pharmacological treatment.

Adolescent↗

PubMed2004

Correlation between cerebral MRI abnormalities and mental retardation in patients with mucopolysaccharidoses.

Mucopolysaccharidoses (MPSs) are a group of inherited disorders due to lysosomal enzyme deficiencies which lead to multi-organ accumulation of glycosaminoglycans. Some forms of MPS disorders are characterized by various degrees of mental retardation. Magnetic Resonance Imaging (MRI) is the primary imaging technique to detect CNS alterations. The aim of this study is to evaluate the correlation between white matter (WM) alterations and the presence of mental retardation. We analyzed 20 patients with different forms of MPSs, 11 with mental retardation and 9 with a normal cognitive function; all of them underwent brain MRI and received a score on the basis of the alterations (WM alterations; perivascular, subarachnoid, and ventricular space enlargement; abnormalities of the basal ganglia, of the corpus callosum and of the atlanto-axial joint). All patients with mental retardation presented severe WM alterations, while only five out of the nine subjects without mental retardation showed certainly WM abnormalities. As far as the other cerebral abnormalities are concerned, no difference between the two groups has been found. These data seem to show that there is a significant correlation between the presence of WM alterations and mental retardation.

Adolescent↗

PubMed2004

Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia.

OBJECTIVE: Deficits in working memory and in prefrontal cortical physiology are important outcome measures in schizophrenia, and both have been associated with dopamine dysregulation and with a functional polymorphism (Val(108/158)Met) in the catechol O-methyltransferase (COMT) gene that affects dopamine inactivation in the prefrontal cortex. The purpose of the present study was to evaluate in patients with schizophrenia the effect of COMT genotype on symptom variation, working memory performance, and prefrontal cortical physiology in response to treatment with an atypical antipsychotic drug. METHOD: Thirty patients with acute untreated schizophrenia were clinically evaluated with the Positive and Negative Syndrome Scale, underwent COMT Val/Met genotyping, and entered an 8-week prospective study of olanzapine treatment. Twenty patients completed two 3-T functional magnetic resonance imaging scans at 4 and 8 weeks during performance of N-back working memory tasks. RESULTS: There was a significant interaction of COMT genotype and the effects of olanzapine on prefrontal cortical function. Met allele load predicted improvement in working memory performance and prefrontal physiology after 8 weeks of treatment. A similar effect was found also for negative symptoms assessed with the Positive and Negative Syndrome Scale. CONCLUSIONS: These results suggest that a genetically determined variation in prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine.

Adult↗

PubMed2003

3.0 T magnetic resonance in neuroradiology.

Ever since the introduction of magnetic resonance (MR), imaging with 1.5 T has been considered the gold standard for the study of all body areas. Until not long ago, higher-field MR equipment was exclusively employed for research, not for clinical use. More recently, the introduction of 3.0 T MR machines for new and more sophisticated clinical applications has yielded in important benefits, especially in neuroradiology. Indeed, their high gradient power and field intensity allow adjunctive and more advanced diagnostic methodologies to be applied with excellent resolution in a fraction of the time of acquisition compared with earlier machines. The numerous advantages of these machines in terms of higher signal, increased spatial resolution and greater sensitivity, and their few limitations, which can be overcome and anyway do not adversely affect diagnostic efficacy, will make 3.0 T MR systems the gold standard for morphological and functional studies of the brain.

Brain↗

PubMed2003

High field MRI.

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Magnetic Resonance Imaging↗

PubMed2003

fMRI of the auditory system: understanding the neural basis of auditory gestalt.

Functional magnetic resonance imaging (fMRI) has rapidly become the most widely used imaging method for studying brain functions in humans. This is a result of its extreme flexibility of use and of the astonishingly detailed spatial and temporal information it provides. Nevertheless, until very recently, the study of the auditory system has progressed at a considerably slower pace compared to other functional systems. Several factors have limited fMRI research in the auditory field, including some intrinsic features of auditory functional anatomy and some peculiar interactions between fMRI technique and audition. A well known difficulty arises from the high intensity acoustic noise produced by gradient switching in echo-planar imaging (EPI), as well as in other fMRI sequences more similar to conventional MR sequences. The acoustic noise interacts in an unpredictable way with the experimental stimuli both from a perceptual point of view and in the evoked hemodynamics. To overcome this problem, different approaches have been proposed recently that generally require careful tailoring of the experimental design and the fMRI methodology to the specific requirements posed by the auditory research. The novel methodological approaches can make the fMRI exploration of auditory processing much easier and more reliable, and thus may permit filling the gap with other fields of neuroscience research. As a result, some fundamental neural underpinnings of audition are being clarified, and the way sound stimuli are integrated in the auditory gestalt are beginning to be understood.

Auditory Cortex↗