Cláudio Campi de Castro

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.

A voxel-based investigation of regional cerebral blood flow abnormalities in obsessive–compulsive disorder using single photon emission computed tomography (SPECT)

Several functional imaging studies have reported abnormalities of the orbitofrontal and anterior cingulate cortices, striatum and thalamus in obsessive-compulsive disorder (OCD). These studies have often been limited by small patient samples and image analysis methods that rely on region-of-interest (ROI) approaches. We have assessed resting regional cerebral blood flow with 99mTc-ECD SPECT in 26 unmedicated OCD patients and 22 healthy control subjects using the voxel-based Statistical Parametric Mapping method for data analysis. We found a significantly reduced ECD uptake in OCD patients relative to the control subjects in the right lateral orbitofrontal cortex, and in the left dorsal anterior cingulate cortex (P<0.001 two-tailed, uncorrected for multiple comparisons). There were significant positive correlations in the OCD group between the ECD uptake in the left lateral orbitofrontal cortex and ratings for obsessive-compulsive symptoms (OCS), and between the ECD uptake in the right medial orbitofrontal cortex and the ratings for both OCS and depressive symptoms. There were also unpredicted significant ECD uptake increases in the cerebellum in OCD patients, as well as a negative correlation between posterior cingulate ECD uptake and OCS severity (P<0.05, corrected for multiple testing). These results implicate specific subregions of the orbitofrontal and anterior cingulate cortices in the pathophysiology of OCD, as well as suggesting the involvement of other areas not usually included in ROI-based imaging studies. With the incorporation of voxel-based methods and the use of large patient samples, rCBF-SPECT studies may continue to provide valuable information about the functional anatomy of OCD.

Volumetric MRI measurements can differentiate Alzheimer's disease, mild cognitive impairment, and normal aging.

BACKGROUND Volumetric magnetic resonance imaging (MRI) has been extensively studied in the last decade as a method to help with the clinical diagnosis of Alzheimers disease (AD). In recent years, researchers have also started investigating if that technique would be useful to identify individuals with mild cognitive impairment (MCI), differentiating them from AD patients and from normal elderly controls. This research project was planned to assess the accuracy of volumetric MRI to differentiate those groups of individuals. METHOD The investigation involved 39 patients with diagnosis of mild to moderate dementia in AD, according to the criteria of the NINCDS-ADRDA, DSM-III-R, and ICD-10; 21 subjects with complaints of cognitive decline without other psychiatric disorders (MCI); and 20 normal elderly controls. All the subjects were submitted to a standard protocol, including volumetric MRI evaluations. RESULTS The results indicated that all regions of interest measured (amygdala, hippocampus, and parahippocampal gyrus) were significantly different (p < .005) in AD patients compared to MCI subjects and controls. The left volumetric measures (amygdala, hippocampus, and parahippocampal gyrus) were also significantly different between the MCI subjects and controls (p < .05). The discriminant function analysis correctly classified 88.14% of the AD patients and controls, 81.67% of AD patients and MCI subjects, and 80.49% of the MCI subjects and controls. CONCLUSIONS The results suggest that measures of medial temporal lobe regions are useful to identify mild to moderate AD patients and MCI subjects, separating them from normal elderly individuals.

Regional Cerebral Blood Flow Abnormalities in Early-Onset Obsessive-Compulsive Disorder: An Exploratory SPECT Study

OBJECTIVE Recent epidemiological and clinical data suggest that obsessive-compulsive disorder (OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms. The regional cerebral blood flow (rCBF) single photon emission computed tomography (SPECT) technique was used to investigate whether the pathophysiology of OCD differs between early- and late-onset OCD subjects. METHOD Resting rCBF was measured in 13 early-onset (<10 years) and 13 late-onset (>12 years) adult OCD subjects and in 22 healthy controls. Voxel-based rCBF comparisons were performed with statistical parametric mapping. RESULTS Early-onset OCD cases showed decreased rCBF in the right thalamus, left anterior cingulate cortex, and bilateral inferior prefrontal cortex relative to late-onset subjects (p < .0005, uncorrected for multiple comparisons). Relative to controls, early-onset cases had decreased left anterior cingulate and right orbitofrontal rCBF, and increased rCBF in the right cerebellum, whereas late-onset subjects showed reduced right orbitofrontal rCBF and increased rCBF in the left precuneus. In early-onset subjects only, severity of obsessive-compulsive symptoms correlated positively with left orbitofrontal rCBF. CONCLUSIONS rCBF differences in frontal-subcortical circuits between early-onset and late-onset OCD subjects were found, both in location and direction of changes. These results provide preliminary evidence that brain mechanisms in OCD may differ depending on the age at which symptoms are first expressed.

Juvenile rheumatoid arthritis of the knee: evaluation with contrast-enhanced color Doppler ultrasound

Abstract.Background. Contrast-enhanced color Doppler ultrasonography is a non-radiation-bearing tool that can be of value for assessment of inflammatory and vascular synovial changes in juvenile rheumatoid arthritis (JRA). Objectives. To evaluate the effect of contrast-enhanced color Doppler ultrasound (US) in the evaluation of synovial changes in the knees of children with JRA. Materials and methods. Sagittal color Doppler sonograms of 31 knees in 22 patients with JRA and of 10 knees in 5 control subjects were obtained before (at baseline) and after (at peak contrast phase) intravenous injection of SHU 508. Images were assessed for overall mean pixel intensity within the synovial tissue and for peak enhancement ratios {[(mean pixel intensity values at maximum contrast enhancement–unenhanced mean pixel intensity values)/unenhanced mean pixel intensity values] × 100}. The joints were classified into three groups by clinical/laboratory criteria: group A (active disease in the knee), n = 9; group B (quiescent disease with serum chemistry levels of active disease), n = 12 and group C (remission disease), n = 10. Results. Mean color pixel intensity values were markedly increased by the use of US contrast agents in groups A (P = 0.004) and B (P = 0.0001), did not reach statistical significance in group C (P = 0.06) and remained essentially unchanged in the control group (P = 0.25). Enhancement ratios for the three groups of JRA patients were not different (P = 0.38) (mean ± SD, 720 % ± 402 for group A, 731 % ± 703 for group B and 314 % ± 263 for group C). Conclusion. Contrast-enhanced color Doppler imaging holds promise for the detection of active synovial inflammatory disease in subclinical cases of JRA, thereby allowing earlier treatment and improved clinical outcome.

Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer’s disease: a combined MRI and SPECT study

Objective: To investigate the relation between atrophy of the hippocampal region and brain functional patterns during episodic memory processing in Alzheimer’s disease. Patients and methods: Whole brain structural magnetic resonance imaging (MRI) data and single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF) were obtained during a verbal recognition memory task in nine subjects with mild Alzheimer’s disease and 10 elderly healthy controls. Using the statistical parametric mapping approach, voxel based comparisons were made on the MRI data to identify clusters of significantly reduced grey matter concentrations in the hippocampal region in the Alzheimer patients relative to the controls. The mean grey matter density in the voxel cluster of greatest hippocampal atrophy was extracted for each Alzheimer subject. This measure was used to investigate, on a voxel by voxel basis, the presence of significant correlations between the degree of hippocampal atrophy and the rCBF SPECT measures obtained during the memory task. Results: Direct correlations were detected between the hippocampal grey matter density and rCBF values in voxel clusters located bilaterally in the temporal neocortex, in the left medial temporal region, and in the left posterior cingulate cortex during the memory task in the Alzheimer’s disease group (p < 0.001). Conversely, measures of hippocampal atrophy were negatively correlated with rCBF values in voxel clusters located in the frontal lobes, involving the right and left inferior frontal gyri and the insula (p < 0.001). Conclusions: Hippocampal atrophic changes in Alzheimer’s disease are associated with reduced functional activity in limbic and associative temporal regions during episodic memory processing, but with increased activity in frontal areas, possibly on a compensatory basis.

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.

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 Alzheimers 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.

Insight and regional brain volumes in schizophrenia

We have investigated the relationship between insight impairment and regional brain volumes (gray and white matter) in schizophrenia using voxel-based morphometry (VBM). Fifty patients with schizophrenia were evaluated using the Scale for Unawareness of Mental Disorders. Magnetic resonance images were acquired, segmented and spatially normalized using optimized VBM routines. No significant inverse correlations were detected between insight impairment and gray or white matter volumes in the prefrontal region (where significant findings had been predicted a priori), or in any other brain areas. Our results do not support previous hypotheses suggesting a relationship between frontal lobe atrophy and impaired insight in patients with schizophrenia.

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.