Amygdala hyperactivation in untreated depressed individuals

The amygdala participates in the detection and control of affective states, and has been proposed to be a site of dysfunction in affective disorders. To assess amygdala processing in individuals with unipolar depression, we applied a functional MRI (fMRI) paradigm previously shown to be sensitive to amygdala function. Fourteen individuals with untreated DSM-IV major depression and 15 healthy subjects were studied using fMRI with a standardized emotion face recognition task. Voxel-level data sets were subjected to a multiple-regression analysis, and functionally defined regions of interest (ROI), including bilateral amygdala, were analyzed with MANOVA. Pearson correlation coefficients between amygdala activation and HAM-D score also were performed. While both depressed and healthy groups showed increased amygdala activity when viewing emotive faces compared to geometric shapes, patients with unipolar depression showed relatively more activity than healthy subjects, particularly on the left. Positive Pearson correlations between amygdala activation and HAM-D score were found for both left and right ROIs in the patient group. This study provides in vivo imaging evidence to support the hypothesis of abnormal amygdala functioning in depressed individuals. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Relationship between Optical Coherence Tomography, Pattern Electroretinogram and Automated Perimetry in Eyes with Temporal Hemianopia from Chiasmal Compression

PURPOSE. To evaluate the relationship between pattern electroretinogram (PERG) amplitude, macular and retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT), and visual field (VF) loss on standard automated perimetry (SAP) in eyes with temporal hemianopia from chiasmal compression. METHODS. Forty-one eyes from 41 patients with permanent temporal VF defects from chiasmal compression and 41 healthy subjects underwent transient full-field and hemifield (temporal or nasal) stimulation PERG, SAP and time domain-OCT macular and RNFL thickness measurements. Comparisons were made using Student`s t-test. Deviation from normal VF sensitivity for the central 18 of VF was expressed in 1/Lambert units. Correlations between measurements were verified by linear regression analysis. RESULTS. PERG and OCT measurements were significantly lower in eyes with temporal hemianopia than in normal eyes. A significant correlation was found between VF sensitivity loss and fullfield or nasal, but not temporal, hemifield PERG amplitude. Likewise a significant correlation was found between VF sensitivity loss and most OCT parameters. No significant correlation was observed between OCT and PERG parameters, except for nasal hemifield amplitude. A significant correlation was observed between several macular and RNFL thickness parameters. CONCLUSIONS. In patients with chiasmal compression, PERG amplitude and OCT thickness measurements were significant related to VF loss, but not to each other. OCT and PERG quantify neuronal loss differently, but both technologies are useful in understanding structure-function relationship in patients with chiasmal compression. (ClinicalTrials.gov number, NCT00553761.) (Invest Ophthalmol Vis Sci. 2009; 50: 3535-3541) DOI:10.1167/iovs.08-3093

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder ( BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray ( GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P = 0.01, right P = 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P = 0.01) and healthy groups (left P = 0.03, right P = 0.03). The Val/Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (P<0.01). There was a significant main effect of diagnosis on memory function (P = 0.04), but no interaction between diagnosis and genotype was found (P = 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD. Neuropsychopharmacology (2009) 34, 1904-1913; doi: 10.1038/npp.2009.23; published online 18 March 2009

A Voxel-Based Morphometry Study of Frontal Gray Matter Correlates of Impulsivity

Impulsivity is a personality trait exhibited by healthy individuals, but excessive impulsivity is associated with some mental disorders. Lesion and functional, neuroimaging Studies indicate that the ventromedial prefrontal region (VMPFC), including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and medial prefrontal cortex, and the amygdala may modulate impulsivity and aggression. However, no morphometric study has examined the association between VMPFC and impulsivity. We hypothesized that healthy subjects with high impulsivity would have smaller volumes in these brain regions compared with those with low impulsivity. Sixty-two healthy Subjects were Studied (age 35.4 +/- 12.1 years) using a 1.5-T MRI system. The Barratt impulsiveness scale (BIS) was used to assess impulsivity. Images were processed using an optimized voxel-based morphometry (VBM) protocol. We calculated the correlations between BIS scale scores and the gray matter (GM) and white matter (WM) volumes of VMPFC and amygdala. GM volumes of the left and right OFC were inversely correlated with the BIS total score (P = 0.04 and 0.02, respectively). Left ACC GM Volumes had a tendency to be inversely correlated with the BIS total score (P = 0.05. Right OFC GM Volumes were inversely correlated with BIS nonplanning impulsivity, and left OFC GM volumes were inversely correlated with motor impulsivity. There were no significant WM volume correlations with impulsivity. The results Of this morphometry Study indicate that small OFC volume relate to high impulsivity and extend the prior finding that the VMPFC is involved in the circuit modulating impulsivity. HUM Brain Mapp 30:1188-1195, 2009. (C) 2008 Wiley-Liss, Inc.

The effects of bromazepam over the temporo-parietal areas during the performance of a visuomotor task: A qEEG study

This study investigated the effects of bromazepam on qEEG when 14 healthy subjects were asked to perform a visuomotor task (i.e., motor vehicle driving task). The subjects were exposed to two experimental conditions: the placebo (PL) and 6 mg of bromazepam (Br 6 mg), following a randomized, double-blind design on different days. Specifically, we observe absolute power extracted from qEEG data for theta band. We expected to see a decrease in absolute theta power in the temporal and parietal areas due to the influence of bromazepam for the experimental group when compared with the placebo group. We found a main effect for the condition factor for electrodes T3, T4, P3 and P4. We also observed a main effect for the period factor for electrodes P3 and P4. We observed that the ingestion of 6 mg of bromazepam induces different patterns in theta power at the temporal and parietal sites. We concluded that 6 mg of bromazepam was an important factor in the fluctuation of the activities in the temporal and parietal areas. We then hypothesize about the specific role of this drug during the execution of a visuomotor task and within the sensorimotor integration process. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Integration of Cortical Areas during Performance of a Catching Ball Task

The study aimed to elucidate electrophysiological and cortical mechanisms involved in anticipatory actions when healthy subjects had to catch balls in free drop. Specific alpha absolute power changes were measured in quantitative electroencephalography (qEEG). Our hypothesis is that during the preparation of motoraction (i.e.. 2 s before the ball drops) integration occurs among the left medial frontal, left primary somatomotor and left posterior parietal cortices, showing a differentiated activity involving expectation, planning and preparedness. We contend that in right-handers, the left hemisphere takes on a dominant role for the regulation of motor behavior. The sample was composed of 23 healthy right handed subjects (13 men and 10 women), with ages varying between 25 and 40 years old (32.5 +/- 7.5), absence of mental and physical illness. The experiment consisted of a task of catching balls with the right hard in free drop. The three-way ANOVA analysis demonstrated all interaction between moment and position in left-medial frontal cortex (F3 electrode), somatomotor cortex (C3 electrode) and posterior parietal cortex (P3 electrode: p < 0.05). Summarizing, the experimental task enabled the observation of integration among frontal, central and parietal regions. This integration appears to be more predominant in expectation, planning and motor preparation.

Responsiveness of sensorimotor cortex during pharmacological intervention with bromazepam

The aim of this study was to investigate the influence of bromazepam on EEG and the motor learning process when healthy subjects were submitted to a typewriting task. We investigated bromazepam due to its abuse by various populations and its prevalent clinical use among older individuals which are more sensitive to the negative effects of long half-life benzodiazepines. A randomized double-blind design was used with subjects divided into three groups: placebo (n = 13), bromazepam 3 mg (n = 13) and bromazepam 6 mg (n = 13). EEG data comprising theta, alpha and beta bands was recorded before, during and after the motor task. Our results showed a lower relative power value in the theta band in the Br 6 mg group when compared with PL. We also observed a reduction in relative power in the beta band in the Br 3 mg and Br 6 mg when compared with PL group. These findings suggest that Br can contribute to a reduced working memory load in areas related to attention processes. On the other hand, it produces a higher cortical activation in areas associated with sensory integration. Such areas are responsible for accomplishing the motor learning task. The results are an example of the usefulness of integrating electrophysiological data, sensorimotor activity and a pharmacological approach to aid in our understanding of cerebral changes produced by external agents. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Integration of cortical areas during performance of a catching ball task

The study aimed to elucidate electrophysiological and cortical mechanisms involved in anticipatory actions when healthy subjects had to catch balls in free drop; specifically through quantitative electroencephalography (qEEG) alpha absolute power changes. Our hypothesis is that during the preparation of motor action (i.e., 2 s before ball`s drop) occurred integration among left medial frontal, left primary somatomotor and left posterior parietal cortices, showing a differentiated activity involving expectation, planning and preparedness. This hypothesis supports a lateralization of motor function. Although we contend that in right-handers the left hemisphere takes on a dominant role for the regulation of motor behavior. The sample was composed of 23 healthy subjects (13 male and 10 female), right handed, with ages varying between 25 and 40 years old (32.5 +/- 7.5), absence of mental and physical illness, right handed, and do not make use of any psychoactive or psychotropic substance at the time of the study. The experiment consisted of a task of catching balls in free drop. The three-way ANOVA analysis demonstrated an interaction between moment and position in left medial frontal cortex (F3 electrode), somatomotor cortex (C3 electrode) and posterior parietal cortex (P3 electrode: p < 0.001). Summarizing, through experimental task employed, it was possible to observe integration among frontal, central and parietal regions. This integration appears to be more predominant in expectation, planning and motor preparation. In this way, it established an absolute predominance of this mechanism under the left hemisphere. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Impaired interhemispheric interactions in patients with major depression

Previous studies have shown that patients with major depression have an interhemispheric imbalance between right and left prefrontal and motor cortex. We aimed to investigate the interhemispheric interactions in patients with major depression using repetitive transcranial magnetic stimulation (rTMS). Thirteen patients with major depression and 14 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS (applied to the left primary motor cortex) was assessed in the left and right motor cortex and these results were compared with those in healthy subjects. There was a significant difference in the interhemispheric effects between patients with depression and healthy subjects. In healthy subjects, 1 Hz rTMS significantly decreased corticospinal excitability in the stimulated, left hemisphere and increased it in the contralateral, right hemisphere. In depressed subjects, 1 Hz rTMS also decreased corticospinal excitability in the left hemisphere; however, it induced no significant changes in corticospinal excitability in the contralateral, right hemisphere. In addition, there was a significant correlation between the degree of interhemispheric modulation and the severity of the depression as indexed by the Beck Depression Inventory scores. Our findings showing a decreased interhemispheric modulation in patients with major depression are consistent with the notion that mood disorders are associated with slow interhemispheric switching mechanisms.

The role played by the parietoocciptal cortex in the process of sensory-motor integration: An electroencephalographic study

Introduction. A fundamental aspect of planning future actions is the performance and control of motor tasks. This behaviour is done through sensory-motor integration. Aim. To explain the electrophysiological mechanisms in the cortex (modifications to the alpha band) that are involved in anticipatory actions when individuals have to catch a free-falling object. Subjects and methods. The sample was made up of 20 healthy subjects of both sexes (11 males and 9 females) with ages ranging between 25 and 40 years (32.5 +/- 7.5) who were free of mental or physical diseases (previous medical history); the subjects were right-handed (Edinburgh Inventory) and were not taking any psychoactive or psychotropic substances at the time of the study. The experiment consisted in a task in which subjects had to catch freely falling objects. The experiment was made up of six blocks of 15 tests, each of which lasted 2 minutes and 30 seconds before and two seconds after each ball was dropped. Results. An interaction of the factors moment and position was only observed for the right parietooccipital cortex, in the combination of electrodes P4-O2. Conclusion. These findings suggest that the right parietooccipital cortex plays an important role in increasing expectation and swiftness in the process of preparing for a motor task.

Abnormal corpus callosum myelination in pediatric bipolar patients

Background: Decreased signal intensity in the corpus callosum, reported in adult bipolar disorder patients, has been regarded as an indicator of abnormalities in myelination. Here we compared the callosal signal intensity of children and adolescents with bipolar disorder to that of matched healthy subjects, to investigate the hypothesis that callosal myelination is abnormal in pediatric bipolar patients. Methods: Children and adolescents with DSM-lV bipolar disorder (n=16, mean age +/- S.D. = 15.5 +/- 3.4 y) and matched healthy comparison subjects (n=21, mean age +/- S.D.=16.9 3.8 y) underwent a 1.5 T MRI brain scan. Corpus callosuin signal intensity was measured using an Apple Power Mac G4 running NIH Image 1.62 software. Results: Bipolar children and adolescents had significantly lower corpus callosum signal intensity for all callosal sub-regions (genu, anterior body, posterior body, isthmus and splenium) compared to healthy subjects (ANCOVA, all p < 0.05, age and gender as covariates). Limitations: Relatively small sample size. Conclusions: Abnormalities in corpus callosum, probably due to altered myelination during neurodevelopment, may play a role in the pathophysiology of bipolar disorder among children and adolescents. (c) 2007 Elsevier B.V All rights reserved.

Scanning laser polarimetry with enhanced corneal compensation for detection of axonal loss in band atrophy of the optic nerve

PURPOSE: To compare the abilities of scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) and variable corneal compensation (VCC) modes for detection of retinal nerve fiber layer (RNFL) loss in eyes with band atrophy (BA) of the optic nerve. DESIGN. Cross-sectional study. METHODS: Thirty-seven eyes from 37 patients with BA and temporal visual field defect from chiasmal compression and 40 eyes from 40 healthy subjects were studied. Subjects underwent standard automated perimetry and RNFL measurements using an SLP device equipped with VCC and ECC. Receiver operating characteristic (ROC) curves were calculated for each parameter. Pearson correlation coefficients were obtained to evaluate the relationship between RNFL thickness parameters and severity of visual field loss, as assessed by the temporal mean defect. RESULTS: All RNFL thickness parameters were significantly lower in eyes with BA compared with normal eyes with both compensation modes. However, no statistically significant differences were observed in the areas under the ROC curves for the different parameters between GDx VCC and ECC (Carl Zeiss Meditec, Inc, Dublin, California, USA). Structure-function relationships also were similar for both compensation modes. CONCLUSIONS: No significant differences were found between the diagnostic accuracy of GDx ECC and that of VCC for detection of BA of the optic nerve. The use of GDx ECC does not seem to provide a better evaluation of RNFL loss on the temporal and nasal sectors of the peripapillary retina in subjects with BA of the optic nerve.

Immunohistochemical Expression of HLA-DR in the Conjunctiva of Patients Under Topical Prostaglandin Analogs Treatment

Purpose: Subclinical inflammation may be observed in patients, using topical antiglaucomatous drugs. The objective,e of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of a immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. Subjects and Methods: Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides. and Prepared for immunohistochemical analysis. Results: Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression (of HLA-DR in the conjunctiva (mild). After 1 month oil prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was round (P 0.27). Conclusions: The use of prostaglandin analogs eye drops provokes, a reaction, observed by HLA-DR subclinical inflammatory expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used.

Comparison of bioelectrical impedance with skinfold thickness and x-ray absorptiometry to measure body composition in HIV-infected with lipodistrophy

Introduction: Human immunodeficiency virus (HIV)associated lipodystrophy syndrome (LS) includes body composition and metabolic alterations. Lack of validated criteria and tools make difficult to evaluate body composition in this group. Objective: The aim of the study was to compare different methods to evaluate body composition between Brazilians HIV subjects with (HIV+LIPO+) or without LS (HIV+LIPO-) and healthy subjects (Control). Methods: in a cross-sectional analyses, body composition was measured by bioelectrical impedance analysis (BIA), skinfold thickness (SF) and dual-energy x-ray absorptiometry (DXA) in 10 subjects from HIV+LIPO+ group; 22 subjects from HIV+LIPO- group and 12 from Control group. Results: There were no differences in age and body mass index (BMI) between groups. The fat mass (FM) (%) estimated by SF did not correlate with DXA in HIV+LIPO+ group (r = 0,46/p >0,05) and had fair agreement in both HIV groups (HIV+LIPO+ =0,35/ HIV+ LIPO- = 0,40). BIA had significant correlation in all groups (p < 0,05) and strong agreement, meanly in HIV groups, for FM (HIV+LIPO+ = 0,79/ HIV+LIPO- = 0,85/Control = 0,60) and for fat free mass (FFM) (HIV+LIPO+ = 0,93/ HIV+LIPO- = 0,92 / Control = 0,73). Discussion: Total fat mass can be measured by BIA with good precision, but not by SF in HIV-infected patients with LS. Segmental BIA, triciptal SF, circumferences of arms, waist and legs maybe alternatives that need more studies.

Constitutional Telomerase Mutations Are Genetic Risk Factors for Cirrhosis

Some patients with liver disease progress to cirrhosis, but the risk factors for cirrhosis development are unknown. Dyskeratosis congenita, an inherited bone marrow failure syndrome associated with mucocutaneous anomalies, pulmonary fibrosis, and cirrhosis, is caused by germline mutations of genes in the telomerase complex. We examined whether telomerase mutations also occurred in sporadic cirrhosis. In all, 134 patients with cirrhosis of common etiologies treated at the Liver Research Institute, University of Arizona, between May 2008 and July 2009, and 528 healthy subjects were screened for variation in the TERT and TERC genes by direct sequencing; an additional 1,472 controls were examined for the most common genetic variation observed in patients. Telomere length of leukocytes was measured by quantitative polymerase chain reaction. Functional effects of genetic changes were assessed by transfection of mutation-containing vectors into telomerase-deficient cell lines, and telomerase activity was measured in cell lysates. Nine of the 134 patients with cirrhosis (7%) carried a missense variant in TERT, resulting in a cumulative carrier frequency significantly higher than in controls (P = 0.0009). One patient was homozygous and eight were heterozygous. The allele frequency for the most common missense TERT variant was significantly higher in patients with cirrhosis (2.6%) than in 2,000 controls (0.7%; P = 0.0011). One additional patient carried a TERC mutation. The mean telomere length of leukocytes in patients with cirrhosis, including six mutant cases, was shorter than in age-matched controls (P = 0.0004). Conclusion: Most TERT gene variants reduced telomerase enzymatic activity in vitro. Loss-of-function telomerase gene variants associated with short telomeres are risk factors for sporadic cirrhosis. (HEPATOLOGY 2011;53:1600-1607)