Myokines in treatment-naïve patients with cancer-associated cachexia.

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.

Proton spectroscopy in Alzheimer's disease and cognitive impairment no dementia: a community-based study.

OBJECTIVE: To describe the findings of proton magnetic resonance spectroscopy ((1)H-MRS) in Alzheimer's disease (AD) and cognitive impairment, no dementia (CIND) elderly from a community-based sample. METHODS: Thirteen patients with AD, 12 with CIND and 15 normal individuals were evaluated. The (1)H-MRS was performed in the right temporal, left parietal and medial occipital regions studying the metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (mI). The clinical diagnosis was based on standardized cognitive tests - MMSE and CAMDEX - and the results correlated with the (1)H-MRS. RESULTS: Parietal Cho was higher in control individuals and lower in CIND subjects. AD and control groups were better identified by temporal and parietal mI combined with the temporal NAA/Cr ratio. CIND was better identified by parietal Cho. CONCLUSION: The (1)H-MRS findings confirmed the hypothesis that metabolic alterations are present since the first symptoms of cognitively impaired elderly subjects. These results suggest that combining MRS from different cerebral regions can help in the diagnosis and follow-up of community elderly individuals with memory complaints and AD.

Volumetric reduction of the corpus callosum in Alzheimer's disease in vivo as assessed with voxel-based morphometry.

Several recent magnetic resonance imaging studies have employed voxel-based morphometry (VBM) to detect regional gray matter volume abnormalities in Alzheimer's disease (AD). However, investigations of corpus callosum (CC) abnormalities in AD using this automated methodology have been scarce, and no VBM study investigated correlations between regional CC atrophy and cognitive measurements in AD subjects at mild disease stages. We used VBM to compare the topography of CC volume differences between 14 AD subjects (MMSE 14-25) and 14 healthy volunteers. Images were acquired using a 1.5-Telsa scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. Significant CC atrophy was detected in the antero-superior portion of the splenium, the isthmus, the anterior and posterior portions of the CC body, and the rostral portion of the genu. Voxels showing peak statistical difference were all left-sided (P<0.001, uncorrected for multiple comparisons). A cluster of significant positive correlation with MMSE scores was seen on the left anterior CC body. Our results confirm previous findings of diffuse volumetric CC reductions early in the course of AD, and warrant further evaluation of the relevance of atrophic changes in anterior CC portions to the cognitive impairments that characterize the disorder.

Grey matter abnormalities in Brazilians with first-episode psychosis.

BACKGROUND: In low- and middle-income countries people with schizophrenia are reported to experience better outcomes than those in high-income countries. AIMS: To examine structural brain differences in people with first-episode psychosis and controls in Brazil. METHOD: Magnetic resonance imaging using voxel-based morphometry was performed on 122 people with first-episode psychosis and 94 controls. RESULTS: There were significant decreases in grey matter in the left superior temporal and inferior prefrontal cortices, insula bilaterally and the right hippocampal region in first-episode psychosis (P<0.05, corrected for multiple comparisons). The subgroup of people with schizophrenia (n=62) exhibited a similar pattern of decrease in grey matter relative to controls. CONCLUSIONS: Structural abnormalities reported in psychosis in high-income countries are also present in first-episode psychosis in Brazil.

Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness.

BACKGROUND: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. METHODS: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes. RESULTS: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. CONCLUSION: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.

Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have investigated the presence of brain abnormalities in obsessive-compulsive disorder (OCD) but have not produced consistent findings. This might be partly related to their use of a regions-of-interest approach. We assessed gray matter volumes in 19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM). METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with optimized VBM. Statistical comparisons were performed with the general linear model. RESULTS: Significant findings were detected in regions predicted a priori to be implicated in OCD, including increased gray matter in OCD subjects relative to control subjects in posterior orbitofrontal and parahippocampal regions; decreased gray matter in OCD patients in the left anterior cingulate cortex; and inverse correlations between obsessive-compulsive symptom severity and gray matter in the medial thalamus (p < .001, uncorrected for multiple comparisons). Also, an unpredicted site of gray matter reduction in OCD patients in the right parietal associative cortex approached significance (p = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are consistent with previous studies implicating dysfunction of orbitofrontal, cingulate, thalamic, and temporolimbic regions in OCD and suggest that the involvement of the parietal cortex in the pathophysiology of OCD warrants further investigation.

Reduced phospholipid breakdown in Alzheimer's brains: a 31P spectroscopy study.

BACKGROUND: Abnormalities of membrane phospholipid metabolism have been described in Alzheimer's disease (AD). We investigated, with the aid of (31)P magnetic resonance spectroscopy, the in vivo intracerebral availability of phosphomonoesters (PME) and phosphodiesters (PDE) in patients with AD. METHODS: Eighteen outpatients with mild or moderate probable AD and 16 nondemented elderly volunteers were assessed with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and its cognitive subscale of the CAMDEX schedule (CAMCOG). Scans were performed on a 1.5 T magnetic resonance imager addressing a 40-cm(3) voxel in the left prefrontal cortex. Main outcome measures were mean relative peak areas of PME and PDE, which provide an estimate of membrane phospholipid metabolism. RESULTS: PME resonance and the PME/PDE ratio were increased in AD patients as compared to controls (p<0.05). PME was negatively correlated with global cognitive performance as shown by the Mini-Mental State Examination (r(s)=-0.36, p=0.05) and CAMCOG scores (r(s)=-0.49, p=0.007), as well as with discrete neuropsychological functions, namely, memory (r(s)=-0.53, p=0.004), visual perception (r(s)=-0.54, p=0.003), orientation (r(s)=-0.36, p=0.05), and abstract thinking (r(s)=-0.48, p=0.01). CONCLUSIONS: We provide evidence of reduced membrane phospholipid breakdown in the prefrontal cortex of mild and moderately demented AD patients. These abnormalities correlate with neuropsychological deficits that are characteristic of AD.

Relationship between regional cerebral blood flow and separate symptom clusters of major depression: a single photon emission computed tomography study using statistical parametric mapping.

This study examined the relationship between resting regional cerebral blood flow (rCBF) patterns in patients with major depressive disorder (MDD) and specific symptom clusters derived from ratings on the Hamilton Rating Scale for Depression (HRSD) and the Mini Mental State Examination. We hypothesized that the functional activity in frontal, parietal, anterior cingulate, basal ganglia and limbic regions would be related to specific symptom domains. Fifteen patients fulfilling DSM-IV criteria for MDD who were off all psychotropic medications for >4 weeks and 15 normal volunteers were recruited. Single photon emission computed tomography (SPECT) images were obtained after (99m)Tc-ECD injection, and correlations between rCBF patterns and symptom severity ratings were calculated on a voxel-by-voxel basis, using statistical parametric mapping (SPM). Severity of depressive mood was inversely correlated with rCBF in the left amygdala, lentiform nucleus, and parahippocampal gyrus, and directly correlated with rCBF in the right postero-lateral parietal cortex (p < 0.001, uncorrected for multiple comparisons). Insomnia severity was inversely correlated with rCBF in the right rostral and subgenual anterior cingulate cortices, insula and claustrum. Anxiety severity was directly correlated with rCBF in the right antero-lateral orbitofrontal cortex, while cognitive performance was directly correlated with rCBF in the right postero-medial orbitofrontal cortex and in the left lentiform nucleus. Our findings confirmed the prediction that separate symptom domains of the MDD syndrome are related to specific rCBF patterns, and extend results from prior studies that suggested the involvement of anterior cingulate, frontal, limbic and basal ganglia regions in the pathophysiology of MDD.

[Proton spectroscopy in Alzheimer's disease and cognitive impairment not dementia: a community study]. / Espectroscopia de prótons na doença de Alzheimer e no comprometimento cognitivo sem demência: estudo de uma amostra comunitária.

OBJECTIVE: To describe the proton magnetic resonance spectroscopy (1H-ERM) data in Alzheimer's disease (AD) and Cognitive Impairment Not Dementia (CIND) in a community sample. METHOD: We investigated subjects with AD (n=6), CIND (n=7) and normal control (n=7). 1H-ERM was performed with single voxel (8 cm3) placed in temporal, parietal and occipital regions and studied metabolites were: N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI). RESULTS: NAA concentration was higher in control subjects than AD and intermediated in CIND patients. Cho parietal plus occipital and Cr parietal plus Cho occipital classified correctly 92.3% of subjects Control vs AD. Temporal mI classified 78.6% of subjects between Control vs CIND. CONCLUSION: Spectroscopy can be used in the diagnosis and follow-up of individuals with cognitive impairment; evaluation of community subjects may show different patterns of brain metabolites distribution.

Frontal and anterior cingulate activation during overt verbal fluency in patients with first episode psychosis.

OBJECTIVE: Functional neuroimaging studies using phonological verbal fluency tasks allow the assessment of neural circuits relevant to the neuropsychology of psychosis. There is evidence that the prefrontal cortex and anterior cingulate gyrus present different activation patterns in subjects with chronic schizophrenia relative to healthy controls. We assessed the functioning in these brain regions during phonological verbal fluency in subjects with recent-onset functional psychoses, using functional magnetic resonance imaging (FMRI). METHODS: Seven patients with functional psychoses (3 schizophreniform, 4 affective) and 9 healthy controls were studied. We compared functional magnetic resonance images acquired during articulation of words beginning with letters classified as easy for word production in Portuguese. Statistical comparisons were performed using non-parametric tests. RESULTS: There were no differences between patients and controls in task performance. Controls showed greater activation than patients in the left rostral anterior cingulate gyrus and right inferior prefrontal cortex, whereas patients showed stronger activation than controls in a more dorsal part of the anterior cingulate gyrus bilaterally and in a more superior portion of the right prefrontal cortex. CONCLUSION: Our preliminary findings of attenuated engagement of inferior prefrontal cortex and anterior cingulate gyrus in patients with recent onset psychosis during phonological verbal fluency are consistent with those of previous studies. The greater activation found in other parts of the anterior cingulate gyrus and prefrontal cortex in patients may be related to a compensatory response that is required to maintain normal task performance, and suggests a pattern of disorganized activity of different functional anterior cingulate gyrus units in association with psychotic conditions.

Mapping brain volumetric abnormalities in never-treated pathological gamblers.

Several magnetic resonance imaging (MRI) studies to date have investigated brain abnormalities in association with the diagnosis of pathological gambling (PG), but very few of these have specifically searched for brain volume differences between PG patients and healthy volunteers (HV). To investigate brain volume differences between PG patients and HV, 30 male never-treated PG patients (DSM-IV-TR criteria) and 30 closely matched HV without history of psychiatric disorders in the past 2 years underwent structural magnetic resonance imaging with a 1.5-T instrument. Using Freesurfer software, we performed an exploratory whole-brain voxelwise volume comparison between the PG group and the HV group, with false-discovery rate correction for multiple comparisons (p < 0.05). Using a more flexible statistical threshold (p < 0.01, uncorrected for multiple comparisons), we also measured absolute and regional volumes of several brain structures separately. The voxelwise analysis showed no clusters of significant regional differences between the PG and HV groups. The additional analyses of absolute and regional brain volumes showed increased absolute global gray matter volumes in PG patients relative to the HV group, as well as relatively decreased volumes specifically in the left putamen, right thalamus and right hippocampus (corrected for total gray matter). Our findings indicate that structural brain abnormalities may contribute to the functional changes associated with the symptoms of PG, and they highlight the relevance of the brain reward system to the pathophysiology of this disorder.

Penetrance and clinical features of pheochromocytoma in a six-generation family carrying a germline TMEM127 mutation.

CONTEXT: The phenotype of familial pheochromocytoma (PHEO) associated with germline TMEM127 mutations (TMEM127-related PHEO) has not been clearly defined. OBJECTIVE: This study aimed to investigate the penetrance, full phenotypic spectrum and effectiveness of clinical/genetic screening in TMEM127-related PHEO. DESIGN, SETTING, AND PARTICIPANTS: Clinical and genetic screening, and genetic counseling were offered to 151 individuals from a six-generation family carrying a TMEM127 germline mutation in a referral center. INTERVENTION AND MAIN OUTCOME MEASURES: TMEM127 genetic testing was offered to at-risk relatives and clinical surveillance for pheochromocytoma was performed in mutation-positive carriers. RESULTS: Forty seven individuals carried the c.410-2A>C TMEM127 mutation. Clinical data were obtained from 34 TMEM127-mutation carriers followed up for 8.7 ± 8.1 years (range, 1-20 y). Pheochromocytoma was diagnosed in 11 carriers (32%) at a median age of 43 years. In nine patients, symptoms started at 29 years (range, 10-55 y) and two cases were asymptomatic. Tumors were multicentric in five (45%) and bilateral in five (45%) patients. Six patients (54%) had at least one adrenomedullary nodule less than 10 mm. No paragangliomas, distant metastases, or other manifestations were detected. Cumulative penetrance of pheochromocytoma was 0% at 0-20 years, 3% at 21-30 years, 15% at 31-40 years, 24% at 41-50 years, and 32% at 51-65 years. The youngest case was diagnosed at 22 years and the earliest symptoms were reported at age 10. CONCLUSIONS: Tumor multicentricity, nodular adrenomedullary hyperplasia, and the occurrence of symptoms more than a decade earlier than the age at diagnosis are novel findings in TMEM127-related PHEO. The high penetrance of pheochromocytoma in this condition validates the benefits of genetic testing of at-risk relatives. We thus recommend that TMEM127 genetic testing should be offered to at-risk individuals at age 22 years and mutation carriers should undergo clinical surveillance annually.

A voxel-based morphometry study of temporal lobe gray matter reductions in Alzheimer's disease.

Several MRI studies have reported reductions in temporal lobe volumes in Alzheimer's disease (AD). Measures have been usually obtained with regions-of-interest (ROI) drawn manually on selected medial and lateral portions of the temporal lobes, with variable choices of anatomical borders across different studies. We used the fully automated voxel-based morphometry (VBM) approach to investigate gray matter abnormalities over the entire extension of the temporal lobe in 14 AD patients (MMSE 14-25) and 14 healthy controls. Foci of significantly reduced gray matter volume in AD patients were detected in both medial and lateral temporal regions, most significantly in the right and left posterior parahippocampal gyri and the left posterior inferior temporal gyrus/fusiform gyrus (P<0.05, corrected for multiple comparisons). At a more flexible statistical threshold (P<0.001, uncorrected for multiple comparisons), circumscribed foci of significant gray matter reduction were also detected in the right amygdala/enthorinal cortex, the anterior and posterior borders of the superior temporal gyrus bilaterally, and the anterior portion of the left middle temporal gyrus. These VBM results confirm previous findings of temporal lobe atrophic changes in AD, and suggest that these abnormalities may be confined to specific sites within that lobe, rather than showing a widespread distribution.

Widespread electrical cortical dysfunction in schizophrenia.

The purpose of this study was to compare slow cortical electrical activity between healthy and schizophrenic individuals using 123-channel EEG and current density reconstruction (CDR). Twenty-nine healthy subjects and 14 drug-free patients performed three visual paired-associate tasks (verbal, pictorial and spatial). We modeled the generators of the slow potentials (SPs) at their peak amplitude by Lp-norm minimization using individual MRIs to model the volume conductor and source. Activity in each architectonic area of Brodmann was scored with respect to individual maximum current by a percentile method. Resulting scores by cortical area were analyzed by multivariate analysis of variance (MANOVA) with planned comparisons, to search for differences among levels. Results showed a multifocal pattern of current density foci comprising the SP generators, including frontal and posterior cortices in all subjects. A few cortical areas, not exclusively frontal, were observed to significantly differ between groups. Moreover, changes in patients' frontal activity were not exclusively to lower scores or 'hipofrontality': overall effects (all tasks collapsed) included increased electrical activity in right area 10, left 38 and 47 bilaterally, and decreased activity in right area 6 and left areas 39, 21 and 19. A few additional areas showed significantly altered activity only in particular tasks. We conclude that the present method, by preserving individual anatomical and functional information, indicates bidirectional patterns of altered electrical activity in specific cortical association areas in schizophrenia, which are not compatible with the exclusive 'hipofrontality' hypothesis. Our results agree with the hypothesis of schizophrenia as a syndrome resulting from abnormalities in multiple encephalic foci.

Psychotic symptoms in major depressive disorder are associated with reduced regional cerebral blood flow in the subgenual anterior cingulate cortex: a voxel-based single photon emission computed tomography (SPECT) study.

BACKGROUND: Delusions and/or hallucinations are not an uncommon feature in severe major depressive episodes. Functional imaging studies of depression have been widely reported in the literature, but few of these have attempted to investigate the neurophysiological correlates of psychotic symptoms. METHODS: We measured resting regional cerebral blood flow (rCBF) with the (99m)Tc-ECD SPECT technique in patients with major depressive disorder with (n=9) and without (n=12) psychotic features, as well as in a group of healthy volunteers (n=12). Between-group rCBF comparisons were performed using the voxel-based statistical parametric mapping method. RESULTS: Major depressed patients with psychotic features showed decreased rCBF in the left subgenual anterior cingulate cortex relative to both non-psychotic patients and healthy controls (P<0.001 one-tailed, uncorrected for multiple comparisons). Relative to the non-psychotic group, depressed patients with psychotic symptoms also had a focus of decreased rCBF in the right inferior frontal cortex, with the voxel of maximal significance in the insula (P<0.031, corrected for multiple comparisons). A similar pattern of significant between-group rCBF differences between psychotic and non-psychotic patients emerged after covarying the analysis for the confounding influence of overall illness severity. CONCLUSIONS: These results provide preliminary evidence that psychotic symptoms in major depression may be associated with abnormalities in ventral paralimbic regions previously implicated in mood regulation and depression.

Gadolinium-enhanced three-dimensional MR angiography of Takayasu arteritis.

Takayasu arteritis is a form of large vessel vasculitis with a possible autoimmune origin that may cause stenosis of the aorta and its major branches. Six types of Takayasu arteritis are recognized; the type depends on whether the ascending aorta, descending thoracic aorta, abdominal aorta, aortic cervicobrachial branches, or renal arteries are affected. The coronary and pulmonary arteries are also sometimes involved. Clinical features of the disease include diminished or absent pulses, claudication, hypertension, and mesenteric angina. Conventional angiography has been the standard imaging tool for diagnosis and evaluation of Takayasu arteritis, although it demonstrates only the lumen of the vessel. Less invasive cross-sectional methods such as computed tomographic angiography and, more recently, three-dimensional magnetic resonance (MR) angiography can effectively demonstrate thickening of the vessel wall, which may be the earliest manifestation of the disease, occurring before stenosis and dilatation. MR imaging in particular allows better soft-tissue differentiation and can show other signs of inflammation, including mural edema and increased mural vascularity. Other advantages of MR imaging are the lack of iodinated contrast material or ionizing radiation.

The generators of slow potentials obtained during verbal, pictorial and spatial tasks.

The purpose of this study was to test whether slow cortical electrical activity is specific to performance on verbal, pictorial and spatial tasks. Twenty-nine healthy subjects were required to compare pairs of visual stimuli separated by a delay of 2.5 s in a S1-S2 contingent negative variation-type paradigm. Slow potentials (SPs) were recorded by high-resolution EEG (123 channels) and their generators modeled by current density reconstruction using individual MRIs as source space models. Activity in each architectonic area of Brodmann was scored with respect to individual maximum current by a percentile method. Results showed a multifocal pattern of current density foci comprising the SP generators, including frontal and posterior cortices in all subjects, with the most active areas being common to the three tasks. In spite of the intersubject variability in the sets of active areas for each given task, a few cortical areas were observed to discriminate between tasks in a statistically significant way: the verbal task corresponded to stronger electrical activity in right area 45 than the other tasks; the spatial to weaker activity in right area 38 and left area 5 than the other tasks; the pictorial, compared to the spatial task, to stronger activity in left area 39; the verbal, compared to the spatial task, to stronger activity in left area 10, and compared to the pictorial, to weaker activity in right area 20. The present method of SP analysis may aid in the functional mapping of human association cortices in individual cases. We discuss our results emphasizing intersubject variability in cortical activity patterns and the possibility of finding more universal patterns.

Multifocal slow potential generation revealed by high-resolution EEG and current density reconstruction.

In this work we used high-resolution EEG (123 channels) and current density reconstruction (CDR) to analyze the generators of slow potentials (SPs) in 31 healthy individuals. SPs were obtained during a task-performance feedback anticipation paradigm. The task consisted of a visual paired-associate memory test, with correct performance on single trials indicated by pleasant visual stimuli and incorrect performance by an unpleasant sound. We used realistic models of each subject's head based on their magnetic resonance images (MRIs) to estimate the potentials in the intracranial compartments and to define the source space using individual cortical geometry. Source reconstruction was performed by an Lp-norm minimization algorithm. Results showed a multifocal pattern of current density foci in various association cortices, including prefrontal areas 9 and 10 of Brodmann in all subjects. Posterior cortical areas also contributed importantly to the SP, for instance extrastriate area 19 and parietal area 7, in 90% of the subjects. According to our modeling, we conclude that even the pure stimulus-anticipation SP obtained here, as opposed to traditional motor-task contigent negative variation (CNVs), is not exclusively prefrontal in origin, being generated by multiple association areas. We discuss our results with respect to new possibilities in large-scale cortical physiology and with respect to their application in psychiatry.

[Reliability of volumetric measures of mesial temporal structures]. / Confiabilidade de medidas volumétricas de estruturas temporais mesiais.

RATIONALE: The development of reliable techniques for volumetric measurement of mesial temporal structures (amygdala, hippocampus and parahippocampal gyrus) on magnetic resonance imaging (MRI) can provide data for the study of neuropsychiatric disorders, mainly temporal lobe epilepsy, Alzheimer's disease and schizophrenia. METHOD: We investigated these techniques performing intraobserver and interobserver reliability study concerning normal controls, epilepsy and Alzheimer's disease patients using the intra-class correlation coefficient. RESULTS: Intra-observer reliability of evaluated structures ranged from 0.93 to 0.99 (p<0.001). Inter-observer reliability ranged from 0.70 to 0.95 (p < or = 0.001). CONCLUSION: The results suggest that the technique of MRI morphometry of mesial temporal regions can be considered a reliable tool which may help in the investigation of neuropsychiatric disorders, since used by adequately trained clinicians and researchers.

Brain activity patterns during phonological verbal fluency performance with varying levels of difficulty: a functional magnetic resonance imaging study in Portuguese-speaking healthy individuals.

A large number of functional neuroimaging studies have investigated the brain circuitry which is engaged during performance of phonological verbal fluency tasks, and the vast majority of these have been carried out in English. Although there is evidence that this paradigm varies depending on the language spoken, it is unclear if this difference is associated with differences in brain activation patterns. Also, there is neuroimaging evidence that the patterns of regional cerebral activation during verbal fluency tasks may vary with the level of task demanded. In particular, the engagement of the anterior cingulate cortex seems to be relative to cognitive demand. We compared functional magnetic resonance imaging data in healthy Portuguese-speaking subjects during overt production of words beginning with letters classified as easy or hard for word production in Portuguese. Compared to the baseline condition, the two verbal fluency tasks (with either easy or hard letters) engaged a network including the left inferior and middle frontal cortices, anterior cingulate cortex, putamen, thalamus and cerebellum (p < .001). The direct comparison between the two verbal fluency conditions showed greater cerebellar activation in the easy condition relative to the hard condition. In the anterior cingulate cortex, there was a direct correlation between activity changes and verbal fluency performance during the hard condition only. Despite grammatical differences, the changes in patterns of brain activity during verbal fluency performance observed in our study are in accordance with findings of previous neuroimaging studies of verbal fluency carried out in English and other languages, with recruitment of a set of distributed cerebral areas during word production.