Tommaso Scarabino

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.

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.

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.

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

IntroductionContrast-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.MethodsThirty-one patients with cerebral gliomas (21 high- and 10 low-grade) underwent conventional MR imaging, proton MR spectroscopic imaging (1H-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 1H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI.ResultsPerienhancing 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 1H-MRSI variables and rCBV better differentiated high- from low-grade gliomas.ConclusionMultiparametric MR assessment of gliomas, based on 1H-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.

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.

Proton MR spectroscopy of cerebral gliomas at 3 T: spatial heterogeneity, and tumour grade and extent

This study aimed to evaluate the usefulness of proton MR spectroscopic imaging (1H-MRSI) at 3 T in differentiating high- from low-grade gliomas, and tumour from necrosis, oedema or normal tissue. Forty-four patients with brain gliomas and four with meningiomas were retrospectively reviewed. The normalised metabolites choline (nCho), N-acetylaspartate (nNAA), creatine (nCr) and lactate/lipids (nLL), and the metabolite ratios Cho/NAA, NAA/Cr and Cho/Cr were calculated. Necrotic-appearing areas showed two spectroscopic patterns: “necrosis” with variable nCho and high nLL, and “cystic necrosis” with variable nLL or nonevident peaks. Peri-enhancing oedematous-appearing areas showed three spectroscopic patterns (“tumour” with abnormal Cho/NAA, “oedema” with normal Cho/NAA and “tumour/oedema” with normal nCho and abnormal Cho/NAA) in gliomas, and one (“oedema”) in meningiomas. Peri-enhancing or peri-tumour normal-appearing areas showed two patterns (“infiltrated” with abnormal nCho and/or Cho/NAA and “normal” with normal spectra) in gliomas and one (“normal”) in meningiomas. Discriminant analysis showed that classification accuracy between high- and low-grade glioma masses was better with normalised metabolites or all parameters together than metabolite ratios and that among peri-enhancing areas was much better with normalised metabolites. The analysis of spatial distribution of normalised metabolites by 3-T 1H-MRSI helps to discriminate among different tissues, offering information not available with conventional MRI.

Carotid stenosis : a comparison between MR and spiral CT angiography

Abstract We performed a preliminary study comparing three-dimensional time-of-flight (3 D TOF) magnetic resonance angiography (MRA) and spiral CT angiography (SCTA) in the detection and assessment of internal carotid artery stenosis. Digital subtraction angiography (DSA) was the reference examination. We examined 20 patients with signs of cerebrovascular insufficiency, who underwent MRA, SCTA and DSA within a 3 day period. Both internal carotid arteries were assessed by three blinded readers for degree of stenosis at two different levels (bulb and remaining section) giving a total of 80 assessments. Interobserver variability, sensitivity, specificity, diagnostic accuracy, concordance, overestimation and underestimation were assessed. Interobserver variability was not statistically significant. MRA showed higher sensitivity, specificity, diagnostic accuracy and concordance than SCTA (92.0 % vs 80.8 %, 98.2 % vs 96.4 %, 96.3 % vs 91.3 % and 96.0 % vs 88.0 %, respectively). MRA gave rise to a 5.0 % overestimation rate, whereas SCTA occasioned a 7.5 % underestimation rate. These differences are not statistically significant. These results suggest that MRA is a more useful, noninvasive modality for assessment of the internal carotid artery with a more than 70 % stenosis.

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.

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.

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.