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ABSTRACT: Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66)Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val(66)Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes. We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val(66) allele, relative to Met(66) carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met(66) carriers relative to Val(66) homozygous during retrieval (but not encoding) while, again, the reverse was true for healthy controls. The Val(66)Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical management of memory deficits in patients with Multiple Sclerosis.
PLoS ONE 01/2013; 8(4):e61063. · 4.09 Impact Factor
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Antonio Cerasa,
Paola Valentino,
Carmelina Chiriaco,
Domenico Pirritano,
Rita Nisticò,
Cecilia M Gioia,
Maria Trotta,
Francesco Del Giudice,
Tiziana Tallarico,
Federico Rocca,
Antonio Augimeri,
Giacinta Bilotti,
Aldo Quattrone
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ABSTRACT: Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system, frequently associated with cognitive impairments. Damages of the cerebellum are very common features of patients with MS, although the impact of this clinical factor is generally neglected. Recent evidence from our group demonstrated that MS patients with cerebellar damages are characterized by selective cognitive dysfunctions related to attention and language abilities. Here, we aimed at investigating the presence of neuroanatomical abnormalities in relapsing-remitting MS patients with (RR-MSc) and without (RR-MSnc) cerebellar signs. Twelve RR-MSc patients, 14 demographically, clinically, and radiologically, matched RR-MSnc patients and 20 controls were investigated. All patients underwent neuropsychological assessment. After refilling of FLAIR lesions on the 3D T1-weighted images, VBM was performed using SPM8 and DARTEL. A correlation analysis was performed between VBM results and neuropsychological variables characterizing RR-MSc patients. Despite a similar clinical status, RR-MSc patients were characterized by more severe cognitive damages in attention and language domains with respect to RR-MSnc and controls. With respect to controls, RR-MSnc patients were characterized by a specific atrophy of the bilateral thalami that became more widespread (including motor cortex) in the RR-MSc group (FWE < 0.05). However, consistent with their well-defined neuropsychological deficits, RR-MSc group showed atrophies in the prefrontal and temporal cortical areas when directly compared with RR-MSnc group. Our results demonstrated that RR-MS patients having cerebellar signs were characterized by a distinct neuroanatomical profile, mainly involving cortical regions underpinning executive functions and verbal fluency.
Journal of Neurology 12/2012; · 3.47 Impact Factor
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Antonio Cerasa,
Maria Cecilia Gioia,
Paola Valentino,
Rita Nisticò,
Carmelina Chiriaco,
Domenico Pirritano,
Francesco Tomaiuolo,
Graziella Mangone,
Maria Trotta,
Tiziana Talarico,
Giacinta Bilotti,
Aldo Quattrone
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ABSTRACT: BACKGROUND: . Although a growing body of evidence has highlighted the role of cognitive rehabilitation (CR) in the management of cognitive dysfunctions in multiple sclerosis (MS), there is still no evidence for a validated therapeutic approach. OBJECTIVE: . We propose a new therapeutic strategy characterized by a computer-based intensive attention training program in MS patients with predominant attention deficits. We aim to investigate the effectiveness of our rehabilitation procedure, tailored for those with impaired abilities, using functional magnetic resonance imaging (fMRI). METHODS: . Using a double-blind randomized controlled study, we enrolled 12 MS patients, who underwent a CR program (experimental group), and 11 age-gender-matched MS patients, who underwent a placebo intervention (control group). fMRI was recorded during the execution of a cognitive task broadly used for assessing attention abilities in MS patients (paced visual serial addition test). RESULTS: . Significant effects were detected both at a phenotypic and at an intermediate phenotypic level. After CR, the experimental group, in comparison with the control group, showed a specific enhanced performance in attention abilities as assessed by the Stroop task with an effect size of 0.88, which was associated with increased activity in the posterior cerebellar lobule and in the superior parietal lobule. CONCLUSIONS: . Our study demonstrates that intensive CR tailored for those with impaired abilities affects neural plasticity and improves some aspects of cognitive deficits in MS patients. The reported neurophysiological and behavioral effects corroborate the benefits of our therapeutic approach, which might have a reliable application in the clinical management of cognitive deficits in MS.
Neurorehabilitation and neural repair 11/2012; · 4.49 Impact Factor
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Daniela Laricchiuta,
Laura Petrosini,
Fabrizio Piras,
Enrica Macci,
Debora Cutuli,
Chiara Chiapponi, Antonio Cerasa,
Eleonora Picerni,
Carlo Caltagirone,
Paolo Girardi,
Stefano Maria Tamorri,
Gianfranco Spalletta
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ABSTRACT: Personality traits are multidimensional traits comprising cognitive, emotional, and behavioral characteristics, and a wide array of cerebral structures mediate individual variability. Differences in personality traits covary with brain morphometry in specific brain regions, and neuroimaging studies showed structural or functional abnormalities of cerebellum in subjects with personality disorders, suggesting a cerebellar role in affective processing and an effect on personality characteristics. To test the hypothesis that cerebellar [white matter (WM) and cortex] volumes are correlated with scores obtained in the four temperamental scales of the Temperament and Character Inventory (TCI) by Cloninger, a total of 125 healthy participants aged 18-67 years of both genders (males = 52) completed the TCI and underwent magnetic resonance imaging. The scores obtained in each temperamental scale were associated with the volumes of cerebellar WM and cortex of right and left hemispheres separately by using linear regression analyses. In line with our hypothesis, novelty seeking (NS) scores were positively associated with WM and cortex cerebellar volumes. Harm avoidance (HA) scores were negatively associated with WM and cortex cerebellar volumes. The range of individual differences in NS and HA scores reflects the range of variances of cerebellar volumes. The present data indicating a cerebellar substrate for some personality traits extend the relationship between personality and brain areas to a structure up to now thought to be involved mainly in motor and cognitive functions, much less in emotional processes and even less in personality individual differences. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 09/2012; · 5.88 Impact Factor
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ABSTRACT: Consistent findings have shown that the cerebellum is critically implicated in a broad range of cognitive processes including executive functions. Of note, cerebellar symptoms and a number of cognitive deficits have been widely reported in patients with multiple sclerosis (MS). This study investigated for the first time the role of cerebellar symptoms in modulating the neural networks associated with a cognitive task broadly used in MS patients (Paced Visual Serial Addition Test (PVSAT)). Twelve relapsing-remitting (RR) MS patients with prevalent cerebellar signs and symptoms (RR-MSc), 15 RR-MS patients without cerebellar manifestation (RR-MSnc) and 16 matched-healthy controls were examined during functional magnetic resonance imaging (fMRI). We tested whether the RR-MSc patients displayed abnormal activations within "cognitive" cerebellar regions and other areas typically engaged in working memory and tightly connected with the cerebellum. Despite similar behavioral performances during fMRI, RR-MSc patients displayed, relatively to both RR-MSnc patients and controls, significantly greater responses in the left cerebellar Crus I/Lobule VI. RR-MSc patients also displayed reduced functional connectivity between the left cerebellar Crus I and the right superior parietal lobule (FWE<.05). These results demonstrated that the presence of the cerebellar signs drastically impacts on the neurofunctional networks underlying working memory in MS. The altered communication between the cerebellum and a cortical area implicated in short-term buffering and storage of relevant information, offer new insights into the pathophysiological mechanisms of cognition in MS.
Experimental Neurology 08/2012; 237(2):418-26. · 4.70 Impact Factor
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ABSTRACT: PURPOSE: Neurodegenerative processes in Parkinson's disease (PD) patients with levodopa-induced dyskinesias (LID) are still a matter of debate. Recently, we demonstrated that this clinical phenotype is associated with an abnormal gray matter increase in the prefrontal cortex when compared to PD without LID. This evidence was found by using voxel-based morphometry (VBM). However, VBM may not be the most appropriate procedure to assess cortical pathology, since its normalization/smoothing steps reduce the ability to anatomically characterize sulci and gyri. The aim of this study is to better delineate the LID-related anatomical abnormalities by using an advanced neuroimaging method that provides a direct and objective measure of the cortical morphology. METHODS: Surface-based investigation of cortical mantle (cortical thickness) was carried out by using Freesurfer in two groups of treated PD patients with LID (no 29) and without LID (no 30), and one group of age- and sex-matched controls (no 24). RESULTS: Cortical thickness analysis revealed a pronounced increase of thickness in the right inferior frontal sulcus in PD patients with LID with respect to PD patients without LID. DISCUSSION: The current study confirms our previous morphological findings on the role of the prefrontal cortex in the pathophysiology of LID and delineates with more precision the anatomical abnormalities characterizing this clinical phenotype.
Parkinsonism & Related Disorders 06/2012; · 3.80 Impact Factor
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Neurology research international. 01/2012; 2012:287891.
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ABSTRACT: Clinical observations and electrophysiological studies have provided initial evidence for the involvement of the cerebellum in essential tremor (ET), the most frequent hyperkinetic disorder. Recently, this hypothesis has been reinvigorated by post-mortem studies that demonstrated a number of pathological changes in the cerebellum of ET patients compared with age-matched healthy controls. Advanced neuroimaging techniques have also made it possible to detect in vivo which cerebellar abnormalities are present in ET patients and to reveal the core mechanisms implicated in the development of motor and cognitive symptoms in ET.
We discuss the neuroimaging research investigating the brain structure and function of ET patients relative to healthy controls. In particular, we review 1) structural neuroimaging experiments assessing the density/volume of cortical/subcortical regions and the integrity of the white-matter fibers connecting them; 2) functional studies exploring brain responses during motor/cognitive tasks and the function of specific neurotransmitters/metabolites within cortical-cerebellar circuits.
A search in PubMed was conducted to identify the relevant literature.
Current neuroimaging research provides converging evidence for the role of the cerebellum in the pathophysiology of ET, although some inconsistencies exist, particularly in structural studies. These discrepancies may depend on the high clinical heterogeneity of ET and on differences among the experimental methods used across studies. Further investigations are needed to disentangle the relationships between specific ET phenotypes and the underlying patterns of neural abnormalities.
Tremor and other hyperkinetic movements (New York, N.Y.). 01/2012; 2.
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ABSTRACT: Psychogenic nonepileptic seizures (PNES) are among the most common clinical manifestations of conversion disorder and consist of paroxysmal behavior that resembles epileptic seizures. Preliminary data from functional neuroimaging studies gave plausible evidence that limbic circuits and sensorimotor cortex might be engaged in conversion disorder. Nonetheless, no advanced magnetic resonance imaging (MRI) studies have focused on patients with PNES.
We enrolled 20 consecutive patients in whom the diagnosis of PNES was based on ictal video-electroencephalography (EEG) of the habitual episodes and 40 healthy subjects matched for age and sex All patients underwent a formal neuropsychological investigation and a neuropsychiatric assessment. All of the patients also underwent two distinct morphologic whole-brain MR measurements, voxel-based morphometry (VBM), and cortical thickness analysis, in a multimethod approach.
None of the patients had serious medical or neurologic illness, substance abuse, or psychotic disorder, or were taking antipsychotic drugs. VBM and cortical thickness analyses in the patients with PNES revealed abnormal cortical atrophy of the motor and premotor regions in the right hemisphere and the cerebellum bilaterally. We also observed a significant association between increasing depression scores and atrophy involving the premotor regions.
The results of this study illustrate that motor and premotor regions in the right hemisphere and the cerebellum bilaterally play an important role in the pathogenesis of PNES and that these structures are correlated with depressive symptoms. Our findings suggest a multistep model in the pathogenesis of PNES, in which the phenomenology is driven by psychological factors interacting with specific biologic abnormalities.
Epilepsia 12/2011; 53(2):377-85. · 3.96 Impact Factor
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ABSTRACT: Levodopa-induced dyskinesia represents disabling complication of long-term therapy with dopaminergic drugs in treating Parkinson's disease (PD). Recently, our group demonstrated that PD patients with levodopa-induced dyskinesia were characterized by abnormal volumetric changes in the inferior prefrontal gyrus. In this study, the functional relevance of this structural abnormality was explored using functional magnetic resonance imaging. Ten dyskinetic PD patients and 10 nondyskinetic PD patients were studied in the OFF phase with functional magnetic resonance imaging while performing externally and internally triggered visuomotor tasks. Although neither group demonstrated behavioral differences during execution of motor tasks, magnetic resonance imaging analysis detected significant changes in target cortical regions. In particular, PD patients with levodopa-induced dyskinesia showed significant overactivity in the supplementary motor area and underactivity in the right inferior prefrontal gyrus during execution of both tasks when compared with PD patients without levodopa-induced dyskinesia. Moreover, these prefrontal functional alterations were significantly correlated with Abnormal Involuntary Movement Scale scores. This functional magnetic resonance imaging study together with our previous volumetric findings highlights the role of the prefrontal cortex in the neuronal mechanisms of dyskinesia.
Movement Disorders 11/2011; 27(3):364-71. · 4.51 Impact Factor
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ABSTRACT: We present a new application based on genetic algorithms (GAs) that evolves a Cellular Neural Network (CNN) capable of automatically determining the lesion load in multiple sclerosis (MS) patients from magnetic resonance imaging (MRI). In particular, it seeks to identify brain areas affected by lesions, whose presence is revealed by areas of higher intensity if compared to healthy tissue. The performance of the CNN algorithm has been quantitatively evaluated by comparing the CNN output with the expert's manual delineation of MS lesions. The CNN algorithm was run on a data set of 11 MS patients; for each one a single dataset of MRI images (matrix resolution of 256×256 pixels) was acquired. Our automated approach gives satisfactory results showing that after the learning process the CNN is capable of detecting MS lesions with different shapes and intensities (mean DICE coefficient=0.64). The system could provide a useful support tool for the evaluation of lesions in MS patients, although it needs to be evolved and developed in the future.
Journal of neuroscience methods 09/2011; 203(1):193-9. · 2.30 Impact Factor
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ABSTRACT: Essential tremor is a common neurological disorder characterized by motor and cognitive symptoms including working memory deficits. Epidemiological research has shown that patients with essential tremor are at a higher risk to develop dementia relative to age-matched individuals; this demonstrates that cognitive impairments reflect specific, although poorly understood, disease mechanisms. Neurodegeneration of the cerebellum has been implicated in the pathophysiology of essential tremor itself; however, whether cerebellar dysfunctions relate to cognitive abnormalities is unclear. We addressed this issue using functional neuroimaging in 15 patients with essential tremor compared to 15 sex-, education- and age-matched healthy controls while executing a verbal working memory task. To remove confounding effects, patients with integrity of the nigrostriatal terminals, no dementia and abstinent from medications altering cognition were enrolled. We tested whether patients displayed abnormal activations of the cerebellum (posterior lobules) and other areas typically engaged in working memory (dorsolateral prefrontal cortex, parietal lobules). Between-groups differences in the interactions of these regions were also assessed with functional connectivity methods. Finally, we determined whether individual differences in neuropsychological and clinical measures modulated the magnitude of regional brain responses and functional connectivity data in patients with essential tremor. Despite similar behavioural performances, patients showed greater cerebellar response (crus I/lobule VI) compared to controls during attentional-demanding working memory trials (F = 8.8; P < 0.05, corrected). They also displayed altered functional connectivity between crus I/lobule VI and regions implicated in focusing attention (executive control circuit including dorsolateral prefrontal cortex, inferior parietal lobule, thalamus) and in generating distracting self-related thoughts (default mode network including precuneus, ventromedial prefrontal cortex and hippocampus) (T-values > 3.2; P < 0.05, corrected). These findings were modulated by the variability in neuropsychological measures: patients with low cognitive scores displayed reduced connectivity between crus I/lobule VI and the dorsolateral prefrontal cortex and enhanced connectivity between crus I/lobule VI and the precuneus (T-values > 3.7; P < 0.05, corrected). It is likely that cerebellar neurodegeneration underlying essential tremor is reflected in abnormal communications between key regions responsible for working memory and that adaptive mechanisms (enhanced response of crus I/lobule VI) occur to limit the expression of cognitive symptoms. The connectivity imbalance between the executive control circuit and the default mode network in patients with essential tremor with low cognitive scores may represent a dysfunction, driven by the cerebellum, in suppressing task irrelevant thoughts via focused attention. Overall, our results offer new insights into pathophysiological mechanisms of cognition in essential tremor and suggest a primary role of the cerebellum in mediating abnormal interactions between the executive control circuit and the default mode network.
Brain 08/2011; 134(Pt 8):2274-86. · 9.46 Impact Factor
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ABSTRACT: In refractory mesial temporal lobe epilepsy (MTLE) extrahippocampal and neocortical abnormalities have been described in patients with or without mesial temporal sclerosis (MTS). Recently we observed gray matter reductions in regions outside the hippocampus in benign MTLE with or without MTS. Cortical thickness has been proposed as a viable methodologic alternative for assessment of neuropathologic changes in extratemporal regions. Herein, we aimed to use this technique to describe cortical abnormalities in patients with benign TLE.
Whole-brain cortical thickness analysis (FreeSurfer) was performed in 32 unrelated patients with benign TLE [16 patients with signs of MTS on magnetic resonance imaging (MRI), pMTLE; 16 without, nMTLE] and 44 healthy controls.
In the pMTLE group, the most significant thinning was found in the sensorimotor cortex bilaterally but was more extensive in the left hemisphere (false discovery rate, p < 0.05). Other areas were localized in the occipital cortex, left supramarginal gyrus, left superior parietal gyrus, left paracentral sulcus, left inferior/middle/superior frontal gyrus, left inferior frontal sulcus, right cingulate cortex, right superior frontal gyrus, right inferior parietal gyrus, right fusiform gyrus, and cuneus/precuneus. In the nMTLE, a similar neurodegenerative pattern was detected, although not surviving correction for multiple comparisons. Direct comparison between pMTLE and nMTLE did not reveal significant changes.
Patients with either benign pMTLE or nMTLE showed comparable cortical thinning, mainly confined to the sensorimotor cortex. This finding that is not appreciated on routine MRI supports the hypothesis that similar to refractory MTLE, even in benign MTLE, pathology in neocortical regions maybe implicated in the pathophysiology of this syndrome.
Epilepsia 03/2011; 52(4):712-7. · 3.96 Impact Factor
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ABSTRACT: Levodopa-induced dyskinesias represent disabling complications from long-term therapy with dopaminergic drugs for treating Parkinson's disease (PD). Although several neuroimaging studies have reported altered striatofrontal function that contributes to the emergence of these motor complications, the neuroanatomical correlates of this disorder are still unknown. Optimized voxel-based morphometry (VBM) was applied to the MRI brain images of 36 PD patients with levodopa-induced dyskinesias, 36 PD patients without levodopa-induced dyskinesias, and 32 age- and sex-matched controls. The VBM analysis comparing dyskinetic and nondyskinetic groups provided evidence of increased gray matter volume of the bilateral inferior frontal gyrus in dyskinetic patients, a finding that was more evident in patients with early-onset PD. No significant differences were detected in the dyskinetic and nondyskinetic groups when compared with the controls. Our findings suggest that the presence of dyskinesias in patients with PD is characterized by an aberrant neural plasticity that could play a role in the pathophysiology of these motor complications.
Movement Disorders 03/2011; 26(5):807-12. · 4.51 Impact Factor
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ABSTRACT: Quantitative analysis of brain atrophy may be useful in differentiating Parkinson's Disease (PD) from Progressive Supranuclear Palsy (PSP) and parkinsonian variant of Multiple System Atrophy (MSA-P); the aim of this study was to identify the volumetric differences of subcortical structures in patients with PD, PSP and MSA-P using a novel and validated fully-automated whole brain segmentation method.
Volumetric MRIs were obtained in 72 patients with PD, 32 patients with PSP, 15 patients with MSA-P, and in 46 control subjects. Subcortical volume was measured automatically by FreeSurfer. Multivariate analysis of covariance, adjusted for intracranial volume (ICV), sex and age, was used to explore group differences.
No volumetric differences were found between PD and controls group; otherwise the volumes of the cerebellum, the thalamus, the putamen, the pallidum, the hippocampus, and the brainstem were significantly reduced in PSP and MSA-P compared to patients with PD and control subjects. PSP and MSA-P patients only differed in thalamus volume which was smaller in PSP group (p < 0.001). Moreover, patients with PSP and MSA-P showed a ventricular system (including lateral, third and fourth ventricles) larger than that detected in PD and controls (p < 0.001).
Volumetric data obtained with automated segmentation of cerebral regions show a significant atrophy of different brain structures in parkinsonisms rather than in PD. Our study also demonstrates that the atrophy of the thalamus only occurs in PSP while the enlargement of the whole ventricular system characterizes both PSP and MSA-P.
Parkinsonism & Related Disorders 03/2011; 17(3):172-6. · 3.80 Impact Factor
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ABSTRACT: The dysbindin (dystrobrevin-binding protein 1) gene has been indicated as one of the most important schizophrenia susceptibility genes. Several genetic variations of this gene have been investigated by using an "intermediate phenotype" approach showing a particular detrimental effect on the prefrontal function in schizophrenic patients. However, the nature of dysbindin function within the brains of healthy individuals is poorly understood, in particular as concerns brain anatomy. We examine relationships between a previously implicated three marker C-A-T dysbindin haplotype and regional cortical thickness in a wide population genotyped for risk carriers (n=14) and non-risk carriers (n=93). Surface-based analysis of the cortical mantle showed that the dysbindin haplotype was associated with structural differences in the medial orbitofrontal cortex, where the risk carriers showed the highest cortical thickness values and the non-risk carriers the lowest. Our study extends previous evidence found on schizophrenic patients to the healthy population, demonstrating the influence of dysbindin risk variants on the neuronal architecture of a specific brain region relevant to the neuropathology of schizophrenia.
NeuroImage 03/2011; 55(2):508-13. · 5.89 Impact Factor
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Rosalucia Mazzei,
Carmine Ungaro,
Girolamo Garreffa,
Francesca Luisa Conforti,
Antonella Mollo,
Teresa Sprovieri,
Pasquale Servillo,
Vincenzo Blasi,
Olivier Gallo, Antonio Cerasa,
Pier Luigi Lanza,
Aldo Quattrone
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ABSTRACT: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a neurometabolic disease characterized by the presence of elevated levels of 2-hydroxyglutaric acid in the plasma, cerebrospinal fluid and urine. Clinical features in this inherited condition consist of mental deterioration, ataxia and motor deficits with pyramidal and extrapyramidal symptoms and signs. L-2-HGA is caused by mutations in the L-2-HGDH gene which most probably encodes for a L-2-hydroxyglutarate dehydrogenase, a putative mitochondrial protein converting L-2-hydroxyglutarate to alphaketoglutarate. Here, we report a pathogenic nonsense mutation in the L-2-HGDH gene found for the first time in an Italian patient affected by L-2-HGA, reinforcing the previously described phenotype of this rare metabolic disease and confirming the data indicating that mutations in the L-2-HGDH gene cause L-2-HGA.
Neurological Sciences 02/2011; 32(1):95-9. · 1.32 Impact Factor
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ABSTRACT: The X-linked Monoamine Oxidase A (MAO A) gene presents a well known functional polymorphism consisting of a variable number of tandem repeats (VNTR) (long and short variants) previously associated with altered neural function of the amygdala. Using automatic subcortical segmentation (Freesurfer), we investigated whether amygdala volume could be influenced by this genotype. We studied 109 healthy subjects (age range 18-80 years; 59 male and 50 female), 74 carrying the MAO A High-activity allele and 35 the MAO A Low-activity allele. No significant effect of the MAO A polymorphism or interaction effect between polymorphism × gender was found on amygdalar volume. Thus, our findings suggest that the reported impact of the MAO A polymorphism on amygdala function is not coupled with consistent volumetric changes in healthy subjects. Future studies are needed to investigate whether the association between volume of the amygdala and the MAO A VNTR polymorphism is influenced by social/psychological variables, such as impulsivity, trauma history and cigarette smoking behaviour, not taken into account in this work.
Psychiatry Research 02/2011; 191(2):87-91. · 2.52 Impact Factor
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ABSTRACT: A functional variant in the mono-amine oxidase A (MAO A) gene has been shown to impact neural function related to cognitive and affective processing and increase risk for conduct disorders. However, whether MAO A could be a candidate gene for structural variation in the human brain remains to be clarified. This study is the first to investigate the effect of this genotype on brain morphology by measuring cortical thickness. We genotyped 59 healthy male subjects (36 carrying the MAO A High-activity allele and 23 the MAO A Low-activity allele) who underwent structural MRI at 3T. Models of the grey-white and pial surfaces were generated for each individual's cortices, and the distance between these two surfaces was used to compute cortical thickness within a priori regions of interest of the orbitofrontal and cingulate cortices. Surface-based analysis of the cortical mantle showed that the MAO A genotype was associated with structural differences in the orbitofrontal cortex bilaterally, where the MAO A High-activity group showed the highest cortical thickness value and the MAO A Low-activity group the lowest. Otherwise, no significant difference was detected within the cingulate cortex. Thus, we confirm the hypothesis that the MAO A genotype has a specific impact on human brain morphology. In particular, thickness measurement of the orbitofrontal cortex provides new evidence about the biological impact of the MAO A genotype on neural systems relevant to the pathophysiology of behavioural disorders.
Behavioural brain research 03/2010; 211(1):118-24. · 3.22 Impact Factor
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ABSTRACT: Cortical thickness has been proposed as a new promising brain imaging endophenotype in elucidating the nature of gene-brain relationships. Here, we define the morphological impact of the Val(158)Met polymorphism in the catechol-O-methyltransferase (COMT) gene on human brain anatomy. One hundred and forty-nine adult healthy subjects (mean age: 40.7+/-16.1; ranging from 19 to 76 years) were genotyped (38 in the homozygous Val(158) group; 80 in the Val(158)Met group; 31 in the homozygous Met(158) group) for the COMT polymorphism and underwent morphological examination. Surface-based analysis of the cortical mantle showed that the COMT genotype was associated with structural differences in the right superior temporal sulcus and inferior prefrontal sulcus, where the individuals carrying the Met(158) allele had a thicker cortex with respect to their Val(158) counterparts. Our study extends the previous evidence found on pediatric population to the adult population, demonstrating that the higher synaptic dopamine levels associated with the presence of the Met(158) allele may influence neuronal architecture in brain structures important for executive and emotional processing.
Neuroscience 02/2010; 167(3):809-14. · 3.38 Impact Factor
