Cortical thickness is related to working memory performance after non-invasive brain stimulation.

Non-invasive brain stimulation (NIBS) probing the dorsolateral prefrontal cortex (DLPFC) has been shown to have little effect on working memory. The variability of NIBS responses might be explained by inter-subject brain anatomical variability. We investigated whether baseline cortical brain thickness of regions of interest was associated with working memory performance after NIBS by performing a secondary analysis of previously published research. Structural magnetic resonance imaging data were analyzed from healthy subjects who received transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and placebo. Twenty-two participants were randomly assigned to receive all the interventions in a random order. The working memory task was conducted after the end of each NIBS session. Regions of interest were the bilateral DLPFC, medial prefrontal cortex, and posterior cingulate cortex. Overall, 66 NIBS sessions were performed. Findings revealed a negative significant association between cortical thickness of the bilateral dorsolateral prefrontal cortex and reaction time for both tDCS (left: P=0.045, right: P=0.037) and iTBS (left: P=0.007, right: P=0.007) compared to placebo. A significant positive association was found for iTBS and posterior cingulate cortex (P=0.03). No association was found for accuracy. Our findings provide the first evidence that individual cortical thickness of healthy subjects might be associated with working memory performance following different NIBS interventions. Therefore, cortical thickness could explain - to some extent - the heterogeneous effects of NIBS probing the DLPFC.

Cortical thickness is related to working memory performance after non-invasive brain stimulation

Non-invasive brain stimulation (NIBS) probing the dorsolateral prefrontal cortex (DLPFC) has been shown to have little effect on working memory. The variability of NIBS responses might be explained by inter-subject brain anatomical variability. We investigated whether baseline cortical brain thickness of regions of interest was associated with working memory performance after NIBS by performing a secondary analysis of previously published research. Structural magnetic resonance imaging data were analyzed from healthy subjects who received transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and placebo. Twenty-two participants were randomly assigned to receive all the interventions in a random order. The working memory task was conducted after the end of each NIBS session. Regions of interest were the bilateral DLPFC, medial prefrontal cortex, and posterior cingulate cortex. Overall, 66 NIBS sessions were performed. Findings revealed a negative significant association between cortical thickness of the bilateral dorsolateral prefrontal cortex and reaction time for both tDCS (left: P=0.045, right: P=0.037) and iTBS (left: P=0.007, right: P=0.007) compared to placebo. A significant positive association was found for iTBS and posterior cingulate cortex (P=0.03). No association was found for accuracy. Our findings provide the first evidence that individual cortical thickness of healthy subjects might be associated with working memory performance following different NIBS interventions. Therefore, cortical thickness could explain - to some extent - the heterogeneous effects of NIBS probing the DLPFC.

Association study of functional polymorphisms of dopaminergic pathway in epilepsy-related factors of temporal lobe epilepsy in Brazilian population.

BACKGROUND AND PURPOSE: There are few data about the role of neurotransmission modulated by dopamine in epilepsy, especially temporal lobe epilepsy (TLE). This is the first study that aimed to analyze the dopaminergic polymorphisms in an etiologically homogeneous group of patients with TLE with hippocampal sclerosis. Selected polymorphisms were: (i) the most expressed D2-like receptors in the limbic system (DRD2/ANKK1 TAQ-1A, D4_VNTR and D4_rs1800955); (ii) the dopamine transporter (DAT) 3'-untranslated region and intron 8; and (iii) two degrading enzymes regulating the synaptic activity, i.e. the main metabolizer of dopamine, catechol-O-methyltransferase, and monoamine oxidase A. METHODS: We assessed 119 patients with unequivocal TLE with hippocampal sclerosis and 112 healthy volunteers. Individuals were genotyped for the polymorphisms of the gene encoding dopaminergic pathway transporter DAT haplotype, dopaminergic receptors, catechol-O-methyltransferase and monoamine oxidase A. We also evaluated epilepsy-related factors (e.g. seizure frequency, age of onset, duration and status epilepticus). RESULTS: There was no difference between the groups for the studied polymorphisms. The polymorphism DRD4_VNTR was associated with family history of epilepsy (P = 0.003), DRD2_rs1800497 was related to status epilepticus (P = 0.022), and intron 8 VNTR DAT was related to higher seizure frequency (P = 0.019) and family history of epilepsy (P = 0.011). CONCLUSIONS: Our findings demonstrated that polymorphisms of the dopaminergic pathway are associated with significant clinical features of this form of epilepsy, such as seizure frequency, family history of epilepsy and status epilepticus.

Neurobiological support to the diagnosis of ADHD in stimulant-naïve adults: pattern recognition analyses of MRI data.

OBJECTIVE: In adulthood, the diagnosis of attention-deficit/hyperactivity disorder (ADHD) has been subject of recent controversy. We searched for a neuroanatomical signature associated with ADHD spectrum symptoms in adults by applying, for the first time, machine learning-based pattern classification methods to structural MRI and diffusion tensor imaging (DTI) data obtained from stimulant-naïve adults with childhood-onset ADHD and healthy controls (HC). METHOD: Sixty-seven ADHD patients and 66 HC underwent high-resolution T1-weighted and DTI acquisitions. A support vector machine (SVM) classifier with a non-linear kernel was applied on multimodal image features extracted on regions of interest placed across the whole brain. RESULTS: The discrimination between a mixed-gender ADHD subgroup and individually matched HC (n = 58 each) yielded area-under-the-curve (AUC) and diagnostic accuracy (DA) values of up to 0.71% and 66% (P = 0.003) respectively. AUC and DA values increased to 0.74% and 74% (P = 0.0001) when analyses were restricted to males (52 ADHD vs. 44 HC). CONCLUSION: Although not at the level of clinically definitive DA, the neuroanatomical signature identified herein may provide additional, objective information that could influence treatment decisions in adults with ADHD spectrum symptoms.

State-dependent microstructural white matter changes in drug-naïve patients with first-episode psychosis.

BACKGROUND: Diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) microstructural abnormalities in schizophrenia. Whether or not such alterations could vary depending on clinical status (i.e. acute psychosis v. remission) remains to be investigated. METHODS: Twenty-five treatment-naïve first-episode psychosis (FEP) patients and 51 healthy-controls (HC) underwent MRI scanning at baseline. Twenty-one patients were re-scanned as soon as they achieved sustained remission of symptoms; 36 HC were also scanned twice. Rate-of-change maps of longitudinal DTI changes were calculated for in order to examine WM alterations associated with changes in clinical status. We conducted voxelwise analyses of fractional anisotropy (FA) and trace (TR) maps. RESULTS: At baseline, FEP presented reductions of FA in comparison with HC [p < 0.05, false-discovery rate (FDR)-corrected] affecting fronto-limbic WM and associative, projective and commissural fasciculi. After symptom remission, patients showed FA increase over time (p < 0.001, uncorrected) in some of the above WM tracts, namely the right anterior thalamic radiation, right uncinate fasciculus/inferior fronto-occipital fasciculus, and left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. We also found significant correlations between reductions in PANSS scores and FA increases over time (p < 0.05, FDR-corrected). CONCLUSIONS: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities in brain tracts are a key neurobiological feature of acute psychotic disorders, and recovery from such WM pathology can lead to amelioration of symptoms.

The influence of lithium on hippocampal volume in elderly bipolar patients: a study using voxel-based morphometry.

Recent studies have demonstrated that lithium (Li) exerts neuronal protective and regenerative effects both in vitro and in vivo. However, the effects of long-term Li treatment in the brain areas associated with memory impairment of elderly bipolar patients are still unknown. The aim of this study was to compare the hippocampal volumes of elderly bipolar patients using Li, elderly bipolar patients not using Li and healthy controls. Sociodemographic, clinical and magnetic resonance imaging data from 30 elderly euthymic bipolar patients who had been using Li for an average of >61 months; 27 elderly euthymic bipolar patients not taking Li for an average of 45 months; and 22 elderly healthy controls were analyzed. Volumetric differences in the hippocampus between groups were investigated with voxel-based morphometry (VBM) based on the Statistical Parametric Mapping technique. No statistical differences in sociodemographic and clinical characteristics and course of bipolar disorder between the two bipolar groups were observed. Using small volume correction in the VBM analysis (analysis of variance (ANOVA)), one voxel cluster of statistical significance was detected in the left hippocampus (P<0.05 corrected for multiple comparisons, extent threshold >10 voxels). Post hoc unpaired t-tests revealed increased left hippocampal volume in the Li-treated group compared with the non-Li-treated group, and decreased left hippocampal volume in the non-Li group relative to controls. Additional exploratory two-group comparisons indicated trends toward reduced right-hippocampal volumes in the non-Li-treated group relative to both the Li-treated group and controls. The findings suggested that the use of Li may influence the volume of the hippocampus, possibly due to its neuroprotective effects.

A Selective Association between Central and Peripheral Lithium Levels in Remitters in Bipolar Depression: A 3T-(7) Li Magnetic Resonance Spectroscopy Study.

OBJECTIVE: The objective of this study was to evaluate brain lithium levels using (7) Li magnetic resonance spectroscopy after 6 weeks of lithium therapy in bipolar depression to test the hypothesis that brain and plasma lithium are correlated. It was also tested whether responders and remitters have different pharmacokinetics, blood and brain lithium levels (ratio) compared with those presenting suboptimal antidepressant improvement. METHOD: Twenty-three patients with bipolar disorder (I and II) during depressive episodes were included and followed up for 6 weeks at the University of Sao Paulo using flexible dose of lithium (450-900 mg/day). Sixteen patients were drug-naïve. At endpoint, patients underwent a (7) Li-MRS scan and brain lithium concentrations were calculated. RESULTS: A significant association between central and peripheral lithium levels was found only in remitters (r = 0.7, P = 0.004) but not in non-remitters (r = -0.12, P = 0.76). Also, brain lithium (but not plasma) was inversely correlated with age (r = -0.46, P = 0.025). Plasma lithium did not correlate with any clinical outcome, lithium dosage or adverse effects. CONCLUSION: These findings suggest that non-remitters may not transport lithium properly to the brain, which may underlie treatment resistance to lithium in BD. Future studies with (7) Li-MRS integrated with the evaluation of blood-brain barrier transport mechanisms and longitudinal clinical outcomes in BD and aging are warranted.

What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis?

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown that brain abnormalities in psychosis might be progressive during the first years of illness. We sought to determine whether first-episode psychosis (FEP) subjects show progressive regional grey matter (GM) changes compared with controls, and whether those changes are associated with diagnosis, illness course or antipsychotic (AP) use. METHOD: Thirty-two subjects with first-episode schizophrenia-spectrum disorders (FESZ), 24 patients with first-episode affective psychoses (FEAP) and 34 controls recruited using a population-based design underwent structural MRI scanning at baseline and at a 5-year follow-up. Regional GM volumes were assessed with voxel-based morphometry (VBM). Patients were treated at community settings, and about half of them remained mainly untreated. RESULTS: No significant progressive changes in GM regional volumes were observed in either the FESZ or FEAP group overall. However, FESZ subjects with a non-remitting course showed GM decrements in the left superior temporal gyrus (STG) and insula relative to remitted FESZ subjects. Non-remitted FEAP subjects exhibited a GM decrease in the dorsolateral prefrontal cortex (DLPFC) bilaterally in comparison to remitted FEAP subjects. Among FESZ subjects, AP use was associated with regional GM decrements in the right insula and increments in the cerebellum. CONCLUSIONS: Our results suggest that the progression of brain abnormalities in FEP subjects is restricted to those with a poor outcome and differs between diagnosis subgroups. AP intake is associated with a different pattern of GM reductions over time.

Healthy individuals treated with clomipramine: an fMRI study of brain activity during autobiographical recall of emotions.

Various functional magnetic resonance imaging studies addressed the effects of antidepressant drugs on brain functioning in healthy subjects; however, none specifically investigated positive mood changes to antidepressant drug. Sixteen subjects with no personal or family history of psychiatric disorders were selected from an ongoing 4-week open trial of small doses of clomipramine. Follow-up interviews documented clear positive treatment effects in six subjects, with reduced irritability and tension in social interactions, improved decision making, higher self-confidence and brighter mood. These subjects were then included in a placebo-controlled confirmatory trial and were scanned immediately after 4 weeks of clomipramine use and again 4 weeks after the last dose of clomipramine. The functional magnetic resonance imaging (fMRI) scans were run during emotion-eliciting stimuli. Repeated-measures analysis of variance of brain activity patterns showed significant interactions between group and treatment status during induced irritability (P<0.005 cluster-based) but not during happiness. Individuals displaying a positive subjective response do clomipramine had higher frontoparietal cortex activity during irritability than during happiness and neutral emotion, and higher temporo-parieto-occipital cortex activity during irritability than during happiness. We conclude that antidepressants not only induce positive mood responses but also act upon autobiographical recall of negative emotions.

Neuroimaging studies of acute effects of THC and CBD in humans and animals: a systematic review.

BACKGROUND: In recent years, growing concerns about the effects of cannabis use on mental health have renewed interest in cannabis research. In particular, there has been a marked increase in the number of neuroimaging studies of the effects of cannabinoids. We conducted a systematic review to assess the impact of acute cannabis exposure on brain function in humans and in experimental animals. METHODS: Papers published until June 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only pharmacological challenge studies involving the acute experimental administration of cannabinoids in occasional or naïve cannabis users, and naïve animals were considered. RESULTS: Two hundred and twenty-four studies were identified, of which 45 met our inclusion criteria. Twenty-four studies were in humans and 21 in animals. Most comprised studies of the acute effects of cannabinoids on brain functioning in the context of either resting state activity or activation during cognitive paradigms. In general, THC and CBD had opposite neurophysiological effects. There were also a smaller number of neurochemical imaging studies: overall, these did not support a central role for increased dopaminergic activity in THC-induced psychosis. There was a considerable degree of methodological heterogeneity in the imaging literature reviewed. CONCLUSION: Functional neuroimaging studies have provided extensive evidence for the acute modulation of brain function by cannabinoids, but further studies are needed in order to understand the neural mechanisms underlying these effects. Future studies should also consider the need for more standardised methodology and the replication of findings.

Longitudinal follow-up of cavum septum pellucidum and adhesio interthalamica alterations in first-episode psychosis: a population-based MRI study.

BACKGROUND: Neurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP). METHOD: FEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination. RESULTS: We found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis×time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis×time interaction. CONCLUSIONS: Our findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study.

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Cervical follicular dendritic cell sarcoma: a case report and review of the literature.

Follicular dendritic cell (FDC) sarcoma is a rare tumour with a low-to-intermediate grade of malignancy. It frequently occurs in cervical, mediastinal and axillary lymph nodes. In approximately 30% of cases an extranodal localization has been reported (tonsils, oral cavity, mediastinum, liver, and spleen). Very little is known about possible treatment options and overall prognosis. This case reports a 66 year-old patient, who underwent surgical removal of a persistently enlarged right cervical lymph node. The histopathological examination revealed a spindle cell tumour with lymphocyte and plasma cell infiltrates. Neoplastic cells stained positive for CD21, CD23 and CD35, thus confirming the diagnosis of FDC sarcoma. The neoplasm recurred two years later and partial regression was achieved by IGEV rescue therapy. We briefly discuss clinical history, histopathological differential diagnosis and treatment options of FDC sarcoma.

Age-related metabolic profiles in cognitively healthy elders: results from a voxel-based [18F]fluorodeoxyglucose-positron-emission tomography study with partial volume effects correction.

BACKGROUND AND PURPOSE: Functional brain variability has been scarcely investigated in cognitively healthy elderly subjects, and it is currently debated whether previous findings of regional metabolic variability are artifacts associated with brain atrophy. The primary purpose of this study was to test whether there is regional cerebral age-related hypometabolism specifically in later stages of life. MATERIALS AND METHODS: MR imaging and FDG-PET data were acquired from 55 cognitively healthy elderly subjects, and voxel-based linear correlations between age and GM volume or regional cerebral metabolism were conducted by using SPM5 in images with and without correction for PVE. To investigate sex-specific differences in the pattern of brain aging, we repeated the above voxelwise calculations after dividing our sample by sex. RESULTS: Our analysis revealed 2 large clusters of age-related metabolic decrease in the overall sample, 1 in the left orbitofrontal cortex and the other in the right temporolimbic region, encompassing the hippocampus, the parahippocampal gyrus, and the amygdala. The division of our sample by sex revealed significant sex-specific age-related metabolic decrease in the left temporolimbic region of men and in the left dorsolateral frontal cortex of women. When we applied atrophy correction to our PET data, none of the above-mentioned correlations remained significant. CONCLUSIONS: Our findings suggest that age-related functional brain variability in cognitively healthy elderly individuals is largely secondary to the degree of regional brain atrophy, and the findings provide support to the notion that appropriate PVE correction is a key tool in neuroimaging investigations.

Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study.

BACKGROUND: Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes. METHOD: Longitudinal regional grey matter volume and ventricle:brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study. RESULTS: While there was no longitudinal difference in ventricle:brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits. CONCLUSIONS: Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.

Neuroimaging in cannabis use: a systematic review of the literature.

BACKGROUND: We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug. METHOD: We reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words: cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy. RESULTS: Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. The functional studies suggest that resting global and prefrontal blood flow are lower in cannabis users than in controls. The results from the activation studies using a cognitive task are inconsistent because of the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls. CONCLUSIONS: Functional neuroimaging studies suggest a modulation of global and prefrontal metabolism both during the resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major effects of cannabis on brain structure has been reported.

Neural activity changes to emotional stimuli in healthy individuals under chronic use of clomipramine.

Previous functional magnetic resonance imaging (fMRI) studies examined neural activity responses to emotive stimuli in healthy individuals after acute/subacute administration of antidepressants. We now report the effects of repeated use of the antidepressant clomipramine on fMRI data acquired during presentation of emotion-provoking and neutral stimuli on healthy volunteers. A total of 12 volunteers were evaluated with fMRI after receiving low doses of clomipramine for 4 weeks and again after 4 weeks of washout. Fear-, happiness-, anger-provoking and neutral pictures from the International Affective Picture System (IAPS) were used. Data analysis was performed with statistical parametric mapping (P < 0.05). Paired t-test comparisons for each condition between medicated and unmedicated states showed, to negative valence paradigms, decrease in brain activity in the amygdala when participants were medicated. We also demonstrated, across both positive and negative valence paradigms, consistent decreases in brain activity in the medicated state in the anterior cingulate gyrus and insula. This is the first report of modulatory effects of repeated antidepressant use on the central representation of somatic states in response to emotions of both negative and positive valences in healthy individuals. Also, our results corroborate findings of antidepressant-induced temporolimbic activity changes to emotion-provoking stimuli obtained in studies of subjects treated acutely with such agents.

Brain structural variability due to aging and gender in cognitively healthy Elders: results from the Sao Paulo Ageing and Health study.

BACKGROUND AND PURPOSE: Several morphometric MR imaging studies have investigated age- and sex-related cerebral volume changes in healthy human brains, most often by using samples spanning several decades of life and linear correlation methods. This study aimed to map the normal pattern of regional age-related volumetric reductions specifically in the elderly population. MATERIALS AND METHODS: One hundred thirty-two eligible individuals (67-75 years of age) were selected from a community-based sample recruited for the São Paulo Ageing and Health (SPAH) study, and a cross-sectional MR imaging investigation was performed concurrently with the second SPAH wave. We used voxel-based morphometry (VBM) to conduct a voxelwise search for significant linear correlations between gray matter (GM) volumes and age. In addition, region-of-interest masks were used to investigate whether the relationship between regional GM (rGM) volumes and age would be best predicted by a nonlinear model. RESULTS: VBM and region-of-interest analyses revealed selective foci of accelerated rGM loss exclusively in men, involving the temporal neocortex, prefrontal cortex, and medial temporal region. The only structure in which GM volumetric changes were best predicted by a nonlinear model was the left parahippocampal gyrus. CONCLUSIONS: The variable patterns of age-related GM loss across separate neocortical and temporolimbic regions highlight the complexity of degenerative processes that affect the healthy human brain across the life span. The detection of age-related limbic GM decrease in men supports the view that atrophy in such regions should be seen as compatible with normal aging.

Engagement of multifocal neural circuits during recall of autobiographical happy events

Happy emotional states have not been extensively explored in functional magnetic resonance imaging studies using autobiographic recall paradigms. We investigated the brain circuitry engaged during induction of happiness by standardized script-driven autobiographical recall in 11 healthy subjects (6 males), aged 32.4 ± 7.2 years, without physical or psychiatric disorders, selected according to their ability to vividly recall personal experiences. Blood oxygen level-dependent (BOLD) changes were recorded during auditory presentation of personal scripts of happiness, neutral content and negative emotional content (irritability). The same uniform structure was used for the cueing narratives of both emotionally salient and neutral conditions, in order to decrease the variability of findings. In the happiness relative to the neutral condition, there was an increased BOLD signal in the left dorsal prefrontal cortex and anterior insula, thalamus bilaterally, left hypothalamus, left anterior cingulate gyrus, and midportions of the left middle temporal gyrus (P < 0.05, corrected for multiple comparisons). Relative to the irritability condition, the happiness condition showed increased activity in the left insula, thalamus and hypothalamus, and in anterior and midportions of the inferior and middle temporal gyri bilaterally (P < 0.05, corrected), varying in size between 13 and 64 voxels. Findings of happiness-related increased activity in prefrontal and subcortical regions extend the results of previous functional imaging studies of autobiographical recall. The BOLD signal changes identified reflect general aspects of emotional processing, emotional control, and the processing of sensory and bodily signals associated with internally generated feelings of happiness. These results reinforce the notion that happiness induction engages a wide network of brain regions.