Sympathovagal quotient and resting-state functional connectivity of control networks are related to gut Ruminococcaceae abundance in healthy men.

INTRODUCTION: Heart rate variability (HRV), brain resting-state functional connectivity (rsFC), and gut microbiota (GM) are three recognized indicators of health status, whose relationship has not been characterized. We aimed to identify the GM genera and families related to HRV and rsFC, the interaction effect of HRV and rsFC on GM taxa abundance, and the mediation effect of diet on these relationships. METHODS: Eighty-eight healthy, young Colombian men were included in this cross-sectional study. HRV metrics were extracted from 24-hour Holter monitoring data and the resting functional connectivity strength (FCS) of 15 networks were derived from functional magnetic resonance imaging. Gut microbiota composition was assessed using the sequences of the V3-V4 regions of the 16 S rRNA gene, and diet was evaluated using a food frequency questionnaire. Multivariate linear regression analyses were performed to evaluate the correlations between the independent variables (HRV metrics and FCS) and the dependent variables (GM taxa abundance or alpha diversity indexes). Mediation analyses were used to test the role of diet in the relationship between HRV and GM. RESULTS: The sympathovagal quotient (SQ) and the FCS of control networks were positively correlated with the abundance of the gut Ruminococcaceae family and an unclassified Ruminococcaceae genus (Ruminococcaceae_unc). Additionally, the interaction between the FCS of the control network and SQ reduced the individual main effects on the Ruminococcaceae_unc abundance. Finally, reduced habitual fiber intake partially mediated the relationship between SQ and this genus. CONCLUSION: Two indicators of self-regulation, HRV and the rsFC of control networks, are related to the abundance of gut microbiota taxa in healthy men. However, only HRV is related to habitual dietary intake; thus, HRV could serve as a marker of food choice and GM composition in the future.

An energy costly architecture of neuromodulators for human brain evolution and cognition.

In comparison to other species, the human brain exhibits one of the highest energy demands relative to body metabolism. It remains unclear whether this heightened energy demand uniformly supports an enlarged brain or if specific signaling mechanisms necessitate greater energy. We hypothesized that the regional distribution of energy demands will reveal signaling strategies that have contributed to human cognitive development. We measured the energy distribution within the brain functional connectome using multimodal brain imaging and found that signaling pathways in evolutionarily expanded regions have up to 67% higher energetic costs than those in sensory-motor regions. Additionally, histology, transcriptomic data, and molecular imaging independently reveal an up-regulation of signaling at G-protein-coupled receptors in energy-demanding regions. Our findings indicate that neuromodulator activity is predominantly involved in cognitive functions, such as reading or memory processing. This study suggests that an up-regulation of neuromodulator activity, alongside increased brain size, is a crucial aspect of human brain evolution.

Genome-wide mapping of brain phenotypes in extended pedigrees with strong genetic loading for bipolar disorder.

Bipolar disorder is a highly heritable illness, associated with alterations of brain structure. As such, identification of genes influencing inter-individual differences in brain morphology may help elucidate the underlying pathophysiology of bipolar disorder (BP). To identify quantitative trait loci (QTL) that contribute to phenotypic variance of brain structure, structural neuroimages were acquired from family members (n = 527) of extended pedigrees heavily loaded for bipolar disorder ascertained from genetically isolated populations in Latin America. Genome-wide linkage and association analysis were conducted on the subset of heritable brain traits that showed significant evidence of association with bipolar disorder (n = 24) to map QTL influencing regional measures of brain volume and cortical thickness. Two chromosomal regions showed significant evidence of linkage; a QTL on chromosome 1p influencing corpus callosum volume and a region on chromosome 7p linked to cortical volume. Association analysis within the two QTLs identified three SNPs correlated with the brain measures.

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants.

The physiological effects of noninvasive brain stimulation fundamentally differ across the human cortex.

Transcranial magnetic stimulation (TMS) is a noninvasive method to modulate brain activity and behavior in humans. Still, stimulation effects substantially vary across studies and individuals, thereby restricting the large-scale application of TMS in research or clinical settings. We revealed that low-frequency stimulation had opposite impact on the functional connectivity of sensory and cognitive brain regions. Biophysical modeling then identified a neuronal mechanism underlying these region-specific effects. Stimulation of the frontal cortex decreased local inhibition and disrupted feedforward and feedback connections. Conversely, identical stimulation increased local inhibition and enhanced forward signaling in the occipital cortex. Last, we identified functional integration as a macroscale network parameter to predict the region-specific effect of stimulation in individual subjects. In summary, we revealed how TMS modulation critically depends on the connectivity profile of target regions and propose an imaging marker to improve sensitivity of noninvasive brain stimulation for research and clinical applications.

Intranetwork and Internetwork Effects of Navigated Transcranial Magnetic Stimulation Using Low- and High-Frequency Pulse Application to the Dorsolateral Prefrontal Cortex: A Combined rTMS-fMRI Approach.

PURPOSE: Although transcranial magnetic stimulation (TMS) is routinely applied in neuroscience and clinical settings, not much is known about its effects on brain networks. Therefore, this pilot study was set up using repetitive navigated transcranial magnetic stimulation (rTMS) combined with resting-state functional MRI (rs-fMRI) to explore frequency-dependent stimulation effects on an intranetwork and internetwork level. METHODS: Six healthy subjects (median age: 23.5 years) underwent two rTMS sessions (1 and 10 Hz), 7 days apart, and prestimulation and poststimulation rs-fMRI. Repetitive navigated transcranial magnetic stimulation was delivered to the left dorsolateral prefrontal cortex, with the exact stimulation target being determined by independent component analysis. Alterations of functional connectivity strength were evaluated using seed-based correlation analyses within and between the salience network, central executive network, and posterior and anterior default mode network. RESULTS: Low-frequency rTMS resulted in significant intranetwork alterations only for the anterior default mode network and primarily within the left hemisphere. In contrast, high-frequency rTMS led to changes within all four networks of interest. Moreover, the posterior and anterior default mode network largely showed opposite effects to rTMS, and the anterior default mode network was rather isolated from the other networks, which was especially true for low-frequency rTMS. Changes in functional connectivity strength because of low-frequency rTMS were even detectable 7 days after stimulation. CONCLUSIONS: This is one of the first studies using neuronavigated TMS with independent component analysis-based target selection to explore frequency-dependent stimulation effects in a combined rTMS-fMRI approach. Future studies including higher subject numbers may define the underlying mechanisms for the different responses to low- and high-frequency rTMS.

Rostral Middle Frontal Volumetric Differences in Bipolar Offspring versus Community Controls Offspring.

Neuroanatomical findings in the anterior limbic network in bipolar disorder (BD) adults have not been replicated in other populations such as bipolar offspring (BO). The aim of this study was to compare some brain areas volumes between BO with and without a lifetime affective disorder (AD) to a group of community control offspring (CCO). Methods: A descriptive observational cross-sectional study was carried out, with multiple comparison groups. Seven subjects (11-17 years old) from the BO with AD group were compared to seven subjects from the BO without AD group and seven subjects from the CCO group (match by age, gender and Tanner stage). Magnetic resonance imaging was performed with a Philips 3 Teslas device and volumetric segmentation was performed with the Freesurfer image analysis suite. Results: A larger size was found in the right middle frontal rostral region in the BO with AD group compared to the other two groups (p = 0.041). A higher volume was also found in BO with AD group in the left pars opercularis (Cohen d = 0.63) and in the right cingulate isthmus (d = 0.53) when compared with BO without AD group, and in the right hippocampus (d = 0.53) when compared to CCO group. A smaller volume was found in the BO without AD group versus CCO group in the left anterior caudate (d = 0.6). The BO groups (with and without AD) compared to CCO have a higher volume in the right frontal pole (d = 0.52). These volumetric differences can be attributed to the condition of BO with AD.

Los hallazgos neuroanatómicos en la red límbica anterior en el trastorno bipolar (TB) en adultos no se han replicado en otras poblaciones, como en los hijos de pacientes con trastorno bipolar (HPTB). El objetivo de este estudio fue comparar los volúmenes de áreas del cerebro entre HPTB, con y sin algún trastorno afectivo (TA) a lo largo de la vida, con un grupo de hijos de padres control de la comunidad (HPC). Métodos: Se realizó un estudio observacional, descriptivo y transversal, con múltiples grupos de comparación. Siete sujetos (11-17 años) del grupo HPTB con TA se compararon con siete sujetos del grupo HPTB sin TA y siete sujetos del grupo HPC (pareados por edad, sexo y estadio Tanner). La resonancia magnética nuclear se realizó con un resonador Philips 3 Teslas y la segmentación volumétrica se realizó con el conjunto de análisis de imagen Freesurfer. Resultados: Se encontró un tamaño mayor en la región frontal rostral medial derecha en el grupo HPTB con TA en comparación con los otros dos grupos (p = 0.041). También se encontró un mayor volumen en el grupo HPTB con TA en el opérculo frontal izquierdo (Cohen d = 0, 63) y en el istmo del giro del cíngulo derecho (d = 0, 53) cuando se comparó con el grupo sin TA, y en el hipocampo derecho (d = 0, 53) en comparación con el grupo HPC. Se encontró un volumen más pequeño en el grupo HPTB sin TA versus grupo HPC en el caudado anterior izquierdo (d = 0, 6). Los grupos HPTB (con y sin TA) en comparación con HPC tienen un volumen mayor en el polo frontal derecho (d = 0.52). Estas diferencias volumétricas pueden atribuirse a la condición de HPTB con TA.

Subjective memory complaints in preclinical autosomal dominant Alzheimer disease.

OBJECTIVE: To cross-sectionally study subjective memory complaints (SMC) in autosomal dominant Alzheimer disease (ADAD). METHODS: We examined self-reported and study partner-based SMC in 52 young, cognitively unimpaired individuals from a Colombian kindred with early-onset ADAD. Twenty-six carried the PSEN-1 E280A mutation, averaging 7 years of age younger than the kindred's expected clinical onset. Twenty-six were age-matched noncarriers. Participants also underwent structural MRI and cognitive testing. RESULTS: Self-reported SMC were greater in carriers than noncarriers (p = 0.02). Study partner-based SMC did not differ between groups (p = 0.21), but in carriers increased with age (r = 0.66, p < 0.001) and decreased with hippocampal volume (r = -0.35, p = 0.08). CONCLUSIONS: Cognitively unimpaired PSEN-1 carriers have elevated SMC. Self-reported SMC may be a relatively early indicator of preclinical AD, while partner- reported SMC increases later in preclinical AD, closer to clinical onset.

Increased hippocampal, thalamus and amygdala volume in long-term lithium-treated bipolar I disorder patients compared with unmedicated patients and healthy subjects.

OBJECTIVE: Magnetic resonance imaging (MRI) studies in bipolar I disorder (BD-I) suggest that lithium is associated with increased volumes of cortico-limbic structures. However, more rigorous control of confounding factors is needed to obtain further support for this hypothesis. The aim of the present study was to assess differences in brain volumes among long-term lithium-treated BD-I patients, unmedicated BD-I patients, and healthy controls. METHODS: This was a cross-sectional study with 32 euthymic BD-I patients (16 on lithium monotherapy for a mean of 180 months, and 16 receiving no medication for at least the 2 months prior to the study) and 20 healthy controls. Patients were euthymic (Hamilton Depression Rating Scale [HDRS] <6 and Young Mania Rating Scale [YMRS] <7) and had not taken psychotropic medications other than lithium for at least 6 months. Brain images were acquired on a 1.5 Tesla MRI (Phillips, Amsterdam, The Netherlands) and segmented to generate volumetric measures of cortical and subcortical brain areas, ventricles and global brain. RESULTS: Significant differences were found in the volumes of the left amygdala (P=.0003), right amygdala (P=.030), left hippocampus (P=.022), left thalamus (P=.022), and right thalamus (P=.019) in long-term lithium-treated BD-I patients, compared to unmedicated patients and controls, after multivariable adjustment. No differences were observed in global brain volume or in ventricular size among the three groups. Likewise, there was no correlation between serum lithium levels and the increase in size in the described brain areas. CONCLUSIONS: The structural differences found among the three groups, and specifically those between long-term lithium-treated and unmedicated BD-I patients, indicate increased limbic structure volumes in lithium-treated patients.

Metabolic connectivity mapping reveals effective connectivity in the resting human brain.

Directionality of signaling among brain regions provides essential information about human cognition and disease states. Assessing such effective connectivity (EC) across brain states using functional magnetic resonance imaging (fMRI) alone has proven difficult, however. We propose a novel measure of EC, termed metabolic connectivity mapping (MCM), that integrates undirected functional connectivity (FC) with local energy metabolism from fMRI and positron emission tomography (PET) data acquired simultaneously. This method is based on the concept that most energy required for neuronal communication is consumed postsynaptically, i.e., at the target neurons. We investigated MCM and possible changes in EC within the physiological range using "eyes open" versus "eyes closed" conditions in healthy subjects. Independent of condition, MCM reliably detected stable and bidirectional communication between early and higher visual regions. Moreover, we found stable top-down signaling from a frontoparietal network including frontal eye fields. In contrast, we found additional top-down signaling from all major clusters of the salience network to early visual cortex only in the eyes open condition. MCM revealed consistent bidirectional and unidirectional signaling across the entire cortex, along with prominent changes in network interactions across two simple brain states. We propose MCM as a novel approach for inferring EC from neuronal energy metabolism that is ideally suited to study signaling hierarchies in the brain and their defects in brain disorders.

Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder.

Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes.

Successful Scene Encoding in Presymptomatic Early-Onset Alzheimer's Disease.

BACKGROUND: Brain regions critical to episodic memory are altered during the preclinical stages of Alzheimer's disease (AD). However, reliable means of identifying cognitively-normal individuals at higher risk to develop AD have not been established. OBJECTIVE: To examine whether functional MRI can detect early functional changes associated with scene encoding in a group of presymptomatic presenilin-1 (PSEN1) E280A mutation carriers. METHODS: Participants were 39 young, cognitively-normal individuals from an autosomal dominant early-onset AD kindred, located in Antioquia, Colombia. Participants performed a functional MRI scene encoding task and a post-scan subsequent memory test. RESULTS: PSEN1 mutation carriers exhibited hyperactivation within medial temporal lobe regions (hippocampus,parahippocampal formation) during successful scene encoding compared to age-matched non-carriers. CONCLUSION: Hyperactivation in medial temporal lobe regions during scene encoding is seen in individuals genetically-determined to develop AD years before their clinical onset. Our findings will guide future research with the ultimate goal of using functional neuroimaging in the early detection of preclinical AD.

Multisystem component phenotypes of bipolar disorder for genetic investigations of extended pedigrees.

IMPORTANCE: Genetic factors contribute to risk for bipolar disorder (BP), but its pathogenesis remains poorly understood. A focus on measuring multisystem quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that affect BP as well as its component phenotypes. OBJECTIVE: To identify quantitative neurocognitive, temperament-related, and neuroanatomical phenotypes that appear heritable and associated with severe BP (bipolar I disorder [BP-I]) and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN, SETTING, AND PARTICIPANTS: Multigenerational pedigree study in 2 closely related, genetically isolated populations: the Central Valley of Costa Rica and Antioquia, Colombia. A total of 738 individuals, all from Central Valley of Costa Rica and Antioquia pedigrees, participated; among them, 181 have BP-I. MAIN OUTCOMES AND MEASURES: Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging, and diffusion tensor imaging phenotypes. RESULTS: Of 169 phenotypes investigated, 126 (75%) were significantly heritable and 53 (31%) were associated with BP-I. About one-quarter of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions as well as volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I association within families that is consistent with expectations from case-control studies. Together, these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder.

Assessment of cardiac volumes using an isotropic whole-heart dual cardiac phase sequence in pediatric patients.

PURPOSE: To evaluate the accuracy of a three-dimensional dual phase (3D DP) whole-heart technique for cardiac volumetric assessment in pediatric patients with cardiac abnormalities. MATERIALS AND METHODS: The institutional approved this study, and informed consent was obtained from patients or their guardians. This prospective study involved 31 pediatric patients (mean age, 7.9 years; range, 15 days to 15 years) for the assessment of cardiac abnormalities using cardiovascular MR. A standard protocol was performed for assessing cardiac anatomy and function. For evaluating the 3D DP technique, statistical comparison with a 2D cine multi-slice technique (2D steady-state free-precession [SSFP]) was performed using linear regression, intraclass correlation coefficient, and Bland Altman plots. RESULTS: Left (LV) and right (RV) ventricular cardiac volumes obtained with the 3D DP technique were in strong agreement with those obtained with the 2D SSFP technique for small and large ventricular volumes. The intraclass correlation coefficients (ICC) between both techniques were 0.992 for the LV end-diastolic volume (EDV), 0.983 for the LV end-systolic volume (ESV), 0.952 for the LV-systolic volume (SV), 0.992 for the RV-EDV, 0.992 for the RV-ESV, 0.928 for the RV-SV. Interobserver analysis indicated good reproducibility for both the 2D SSFP and the 3D DP techniques. CONCLUSION: The 3D DP technique provides as accurate cardiac volumes as the 2D SSFP technique in the pediatric population, but with the added benefits of easier data acquisition and detailed anatomical information of the whole heart and great vessels in a single free-breathing scan.

Angiografía no contrastada con Arterial Spin Labeling / Non-contrast angioresonance with Arterial Spin Labeling

Introducción: La angiografía por resonancia magnética no contrastada realizada con "Arterial Spin Labeling" (ARM ASL) es un método diseñado para marcar los espines sanguíneos y así crear un contraste endógeno adecuado para evaluar territorios vasculares selectivamente sin la necesidad de aplicar medio de contraste intravenoso (compuestos de Gadolinio). Metodología: Se realizó un estudio descriptivo de una serie de casos, donde se describen los detalles técnicos y los resultados de la aplicación de la ARM ASL en equipos de 1.5 y 3 Tesla en voluntarios sanos. Resultados: Se observaron dos casos: Para la técnica angiográfica del primer caso (ASL "Flow-in") se usó un resonador de 3T, sincronización cardiaca, una secuencia b-SSFP 3D y un pre-pulso de inversión, este último para saturar los tejidos estáticos. El volumen de examen se ubicó en el plano axial teniendo la precaución de cubrir la anatomía vascular renal, lo cual se logra en la mayoría de los casos con 60 a 70 cortes de 2 mm solapados en 50 porciento, voxel de 2x1x1 mm y campo de visión (FOV) de 250x100 mm. El protocolo del segundo caso fue obtenido en un equipo de 1.5T, sin sincronización cardiaca, con un navegador respiratorio dia fragmático y con una secuencia coronal Turbo SE 3D después de aplicar dos pre-pulsos de marcación sanguínea, el primero similar al del caso anterior y el segundo, o pulso selectivo, para marcar el flujo del vaso de interés. Con este método (ASL "Flow-Out") sólo la sangre marcada emite señal. Conclusión: Las técnicas de angiografía b-SSFP 3D y Turbo SE 3D no contrastadas con pre-pulsos de ASL en 1.5 y 3T son alternativas disponibles y, por lo tanto, pueden considerarse como complemento a otros métodos de angiografía por resonancia magnética al momento de evaluar la patología vascular.

Introduction: Non-contrast magnetic resonance angiography using "Arterial Spin Labeling" (MRA ASL) is a technique designed to label blood spins and therefore create an endogenous contrast suitable for selectively evaluating vascular territories without intravenous contrast (Gadolinium compounds). Methodology: Technical details and results of the implementación of the MRA ASL using 1.5 and 3.0 Tesla systems in healthy volunteers is described. Results: Two cases were observed: for the angiographic technique of the first case (ASL "Flow-in") in a 3.0 T unit, cardiac synchronization (cardiac gating), a 3D b-SSFP sequence, and an inversion pre-pulse was used, the latter to saturate the static tissues. The examination volume was located in the axial plane taking care to cover the renal vascular anatomy, which is achieved in most cases with 60 to 70 2 mm slices overlapped in 50%, voxel of 2x1x1 mm and a field of vision (FOV) of 250 x100 mm. The protocol for the second case was obtained on a 1.5 T system, without cardiac gating, with a diaphragmatic respiratory navigator and a 3D Turbo SE coronal sequence after applying two pre-pulse blood saturation bands, the first similar to the previous case and the second, or selective pulse, to label the flow of the vessel of interest. With this method (ASL "Flow-Out") only the labeled blood emits a signal. Discussion: 3D b-SSFP and 3D Turbo SE non-contrast angiography techniques with ASL pre-pulses in 1.5 and 3T are available alternatives and, therefore, can be considered as a complement to other methods of magnetic resonance angiography when assessing vascular pathology.

[Correlation between the magnetic resonance imaging morphometry and the clinical and electroencephalographic findings in patients diagnosed with ulegyria and epilepsy]. / Correlación de la morfometría por resonancia magnética con los hallazgos clínicos y electroencefalográficos de pacientes con diagnóstico de ulegiria y epilepsia.

INTRODUCTION: Ulegyria is a cortical lesion affecting neighbouring vascular zones, which gives the convolutions a mushroom-like appearance. It is an important cause of occipital epilepsy. AIM. To correlate patients diagnosed clinically, electrically and morphometrically with ulegyria and epilepsy by comparing the thickness of the cortex in the zones affected by ulegyria with the normal cortical thickness reported in the literature and the average cortical thickness of healthy subjects. PATIENTS AND METHODS: Ten patients with ulegyria confirmed by magnetic resonance imaging were included in the study; all of them were submitted to a clinical interview, an electroencephalographic study and cortical morphometric analysis based on volumetric T1 sequences. RESULTS: Findings included a predominance in males, neurodevelopmental retardation and epilepsy. Ulegyria was mainly parietooccipital, frequently bilateral, with statistically significant thinning of the cortical thickness in the site of the lesion and an increase in the thickness of the cortex in the areas surrounding the lesion. CONCLUSIONS: We report on a series of patients with ulegyria with characteristics similar to those existing in the literature and by means of morphometry we detected an increase in the thickness of the cortex around the areas affected by ulegyria. These findings could point to the presence of adaptive neuroplasticity in the neurons that surround the scar tissue or they may be the result of mechanical changes of normal tissue in response to the loss of volume of the ulegyria-affected area, although these data need to be replicated in a study with a greater number of patients.

Informatics in radiology: use of CouchDB for document-based storage of DICOM objects.

Picture archiving and communication systems traditionally have depended on schema-based Structured Query Language (SQL) databases for imaging data management. To optimize database size and performance, many such systems store a reduced set of Digital Imaging and Communications in Medicine (DICOM) metadata, discarding informational content that might be needed in the future. As an alternative to traditional database systems, document-based key-value stores recently have gained popularity. These systems store documents containing key-value pairs that facilitate data searches without predefined schemas. Document-based key-value stores are especially suited to archive DICOM objects because DICOM metadata are highly heterogeneous collections of tag-value pairs conveying specific information about imaging modalities, acquisition protocols, and vendor-supported postprocessing options. The authors used an open-source document-based database management system (Apache CouchDB) to create and test two such databases; CouchDB was selected for its overall ease of use, capability for managing attachments, and reliance on HTTP and Representational State Transfer standards for accessing and retrieving data. A large database was created first in which the DICOM metadata from 5880 anonymized magnetic resonance imaging studies (1,949,753 images) were loaded by using a Ruby script. To provide the usual DICOM query functionality, several predefined "views" (standard queries) were created by using JavaScript. For performance comparison, the same queries were executed in both the CouchDB database and a SQL-based DICOM archive. The capabilities of CouchDB for attachment management and database replication were separately assessed in tests of a similar, smaller database. Results showed that CouchDB allowed efficient storage and interrogation of all DICOM objects; with the use of information retrieval algorithms such as map-reduce, all the DICOM metadata stored in the large database were searchable with only a minimal increase in retrieval time over that with the traditional database management system. Results also indicated possible uses for document-based databases in data mining applications such as dose monitoring, quality assurance, and protocol optimization.

Efecto de la medicación en los patrones de activación cerebral en resonancia magnética funcional, ante un paradigma de memoria de trabajo en pacientes con trastorno bipolar tipo I / Effects of Medication on fMRI Brain Activation Patterns in Bipolar Disorder Type I Patients Challenged with Working Memory Tasks

Introducción: Diversos estudios demuestran un aumento en la activación de áreas límbicas y paralímbicas y disminución de la activación en áreas relacionadas con la memoria de trabajo en pacientes con trastorno bipolar. La mayoría de estos estudios se realizan en pacientes que reciben tratamiento farmacológico, lo cual dificulta interpretar hasta qué punto el tratamiento es responsable de las alteraciones encontradas. Objetivo: Identificar las posibles diferencias en la respuesta neurofuncional de pacientes con trastorno bipolar en tareas de memoria operativa y establecer el papel de la medicación en estas diferencias. Metodología: Estudio descriptivo-correlacional de corte transversal. Se evaluaron 43 individuos, de los cuales 33 fueron pacientes eutímicos con trastorno bipolar tipo I (13 en tratamiento con carbonato de litio, 9 con ácido valpróico y 10 sin medicación al menos durante dos meses previos a la evaluación) y 11 controles. La resonancia magnética funcional (RMf) se usó para correlacionar sus procesos de memoria operativa con los cambios vistos en la señal BOLD, usando un paradigma que combina la presentación de bloques y eventos relacionados. Resultados: No se encontraron diferencias significativas en las variables clínicas o demográficas entre los grupos, excepto en el puntaje de la Young Mania Rating Scale (YMRS). Se encontraron diferencias en el patrón de activación del cíngulo anterior al comparar los pacientes bipolares y los controles (p=0,05). Conclusión: Se encontraron diferencias en el patrón de activación del cíngulo anterior en la RMf en una prueba de memoria de trabajo comparando los pacientes bipolares tipo I y los controles.

Background: Patients with bipolar disorder show increased activation in limbic and para-limbic areas whereas they show decreased activity in working memory-related areas. The degree to which pharmacological treatment determines these alterations is hard to gage, given that most studies have been done on patients already receiving such treatments. Objective: We seek to identify differences and the role of treatment in neurofunctional response in patients with bipolar disorder type I compared to controls, specifically while challenged with working memory tasks. Methods: Thirtythree euthymic patients with type I bipolar disorder and 10 controls were evaluated in a cross-sectional study; 13 of them were being treated with lithium, 9 with valproic acid, and 10 had not received treatment for at least 2 months prior to the study. Correlation was established between functional Magnetic Resonance (fMRI) BOLD signal and working memory processes. Results: There were no significant differences between the groups in demographics or clinical variables except for YMRS score. Patients and controls showed significantly different patterns of brain activation in the anterior cingulate (p:0.05) during working memory tasks. Conclusion: There are statistically significant differences in the anterior cingulate BOLD (Blood oxygen level dependent) signal of patients with Type I Bipolar disorder compared to controls.

Diferencias en la resonancia magnética funcional en pacientes con trastorno bipolar usando un paradigma de memoria de trabajo / Differences in Functional Magnetic Resonance Imaging of Bipolar Patients Using a Working Memory Paradigm

Introducción: Los estudios con pruebas neuropsicológicas han demostrado déficits en la memoria operativa de pacientes con trastorno afectivo bipolar (TAB). Todavía no es clara la correlación de estos déficits con activaciones funcionales detectados con neuroimágenes, como la resonancia magnética funcional (RMf). Objetivo: Describir la aplicación de un nuevo paradigma de evaluación neurocognitiva para identificar las posibles diferencias en las características de respuesta neurofuncional en pacientes con TAB en tareas de memoria operativa. Método: Estudio descriptivo-correlacional de corte transversal. Se evaluaron 12 pacientes eutímicos con TAB tipo I (cuatro en tratamiento con carbonato de litio, cuatro con ácido valproico y cuatro sin medicación al menos durante dos meses previos a la evaluación) y cuatro controles. La RMf se usó para correlacionar sus procesos de memoria operativa con los cambios vistos en la señal BOLD, usando un paradigma que combina la presentación de bloques y eventos relacionados. Resultados: La activación cerebral del grupo control fue significativamente mayor durante su condición de respuesta, comparada con la presentada en pacientes con TAB; pero al contrastar los grupos de pacientes no hubo diferencia estadísticamente significativa (p>0,05). Discusión: El paradigma evaluado es útil en el estudio de áreas de activación cerebral en procesos de memoria operativa. Los resultados diferenciales en pacientes bipolares requieren estudios con muestras más grandes para comparar otros posibles déficits cognitivos asociados y efectos específicos de los medicamentos.

Background: Previous studies with neuropsychological testing have shown deficits in working memory in patients with bipolar disorder (BD). It is not yet clear if there is correlation with functional activation in neuroimaging such as functional Magnetic Resonance Imaging (fMRI). Objective: To describe a new paradigm of neurocognitive assessment to identify the possible differences in the characteristics of neurofunctional response in patients with BD using a working memory task. Method: Descriptive, correlational, cross sectional study. We evaluated 12 euthymic patients with BD-I (in treatment with lithium or valproate or without treatment at least 2 months prior to the study) and 4 participants with no psychiatric disorder. fMRI was used to correlate their operative memory processes with the changes seen in the BOLD signal using a paradigm that combines the presentation of blocks and related events. Results: Control's brain activation was greater during response condition compared with bipolar patients. When comparing between patient groups there was no statistically significant difference (p>0.05). Discussion: The paradigm we deployed is useful to study activation in brain areas involved in working memory processes. The results with bipolar patients need to be expanded with larger populations to compare other possible cognitive deficits and medication specific effects.

Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease.

OBJECTIVE: The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer's disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms. METHODS: Twenty carriers of the Alzheimer's-associated E280A PS1 mutation and 19 PS1-negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face-name associative encoding task while in a Phillips 1.5T fMRI scanner. Analysis focused on the hippocampal system. RESULTS: Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face-name associations compared to matched controls. INTERPRETATION: Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD.