Structural changes after videogame practice related to a brain network associated with intelligence

Here gray and white matter changes after four weeks of videogame practice were analyzed using optimized voxel-based morphometry (VBM), cortical surface and cortical thickness indices, and white matter integrity computed from several projection, commissural, and association tracts relevant to cognition. Beginning with a sample of one hundred young females, twenty right handed participants were recruited for the study and assigned to a practice or a control group carefully matched by their general cognitive ability scores. After the first scan, the practice group played ‘Professor Layton and The Pandora's Box’ 4 h per week during four weeks. A second scan was obtained at the end of practice and intelligence was measured again. Image analyses revealed gray and white matter changes in the practice group. Gray matter changes theoretically relevant for intelligence were observed for the practice group mainly in frontal clusters (Brodmann areas 9 and 10) and also in smaller parietal and temporal regions. White matter findings were focused in the hippocampal cingulum and the inferior longitudinal fasciculus. These gray and white matter changes presumably induced by practice did not interact with intelligence tests' scores.

Grapheme-color synesthetes show peculiarities in their emotional brain: cortical and subcortical evidence from VBM analysis of 3D-T1 and DTI data

Grapheme-color synesthesia is a neurological phenomenon in which viewing achromatic letters/numbers leads to automatic and involuntary color experiences. In this study, voxel-based morphometry analyses were performed on T1 images and fractional anisotropy measures to examine the whole brain in associator grapheme-color synesthetes. These analyses provide new evidence of variations in emotional areas (both at the cortical and subcortical levels), findings that help understand the emotional component as a relevant aspect of the synesthetic experience. Additionally, this study replicates previous findings in the left intraparietal sulcus and, for the first time, reports the existence of anatomical differences in subcortical gray nuclei of developmental grapheme-color synesthetes, providing a link between acquired and developmental synesthesia. This empirical evidence, which goes beyond modality-specific areas, could lead to a better understanding of grapheme-color synesthesia as well as of other modalities of the phenomenon.

Efficacy of Stanozolol on bone regeneration: in vitro and in vivo study

La ricerca di nuove strategie per la rigenerazione ossea rappresenta un focus di interesse centrale per migliorare la gestione di casi clinici complessi nell’ambito della chirurgia orale e maxillo-facciale. Uno degli approcci più utilizzati in tale contesto si basa sull’utilizzo di molecole con proprietà osteoinduttive e molte sostanze sono state fino ad oggi sperimentate. E’ noto in letteratura che gli androgeni svolgono un ruolo chiave nella regolazione della morfogenesi ossea e nel mantenimento della sua omeostasi durante il corso della vita. Questo lavoro di tesi nasce dall’ipotesi che la somministrazione locale di tali ormoni, eventualmente combinata a materiali da innesto, possa favorire la guarigione di difetti ossei. Stando a questa premessa, sono stati valutati gli effetti dello steroide sintetico Stanozololo sulla rigenerazione ossea in diversi settings sperimentali. La tesi è strutturata secondo un percorso che segue le fasi della ricerca, attraverso sperimentazioni in vitro e in vivo; ogni capitolo può essere approcciato come uno studio a sé stante, corrispondente ad una determinata tappa dell’iter sperimentale. Sulla base di questi intenti, viene fornito inizialmente un quadro d’insieme circa gli effetti degli androgeni sull’osso. A seguire, è presentata una sperimentazione in vitro nella linea cellulare SaOS-2. Infine, è proposta un’innovativa metodologia di analisi per lo studio della rigenerazione ossea nel modello di ratto, ove viene testata la somministrazione locale di Stanozololo combinato a materiale da innesto.

Efeito do estresse hídrico sobre a locomoção e morfologia de girinos de Leptodactylus fuscus e Physalaemus nattereri

Diversas espécies de anuros da família Leptodactylidae se reproduzem em corpos dágua sazonais, temporários e mantidos exclusivamente por chuvas. Em períodos de estiagem prolongada a poça pode secar completamente, ocasionando elevadas taxas de mortalidade de ovos e girinos dessas espécies, podendo exercer forte pressão seletiva na evolução de mecanismos de resistência e sobrevivência nas fases iniciais do desenvolvimento. Algumas espécies de girinos conseguem sobreviver cerca de cinco dias fora dágua o que pode proporcionar uma adaptação vantajosa, porque possibilita a sobrevivência dos girinos por um período que pode ser suficiente para a reincidência de novas chuvas e restabelecimento do corpo dágua. Apesar dessa capacidade de sobrevivência, pouco se sabe sobre as possíveis modificações que a desidratação pode causar na locomoção e na morfologia durante o desenvolvimento desses animais. O presente trabalho teve como objetivo avaliar o efeito do estresse hídrico: (1) no nível de sobrevivência e perda de massa corpórea; (2) no desempenho locomotor; (3) na morfologia externa (morfometria linear) e interna, analisando tanto o volume total quanto o volume visceral (estereologia); e (4) no tempo até metamorfose após o estresse. Utilizamos girinos de duas espécies de anuros, Leptodactylus fuscus (Leptodactylinae) e Physalaemus nattereri (Leiuperinae), ambas as espécies se reproduzem em corpos dágua temporários, em áreas com estação seca definida estando, portanto sujeitas as mesmas pressões seletivas. Além disso, as duas espécies apresentam modos reprodutivos diferentes, podendo apresentar diferentes graus de resistência ao estresse hídrico. Os girinos das duas espécies foram divididos em dois grupos, os que ficaram em água (grupo controle) e os que foram submetidos ao estresse hídrico (grupo tratamento), por três períodos de tempo (12, 24 e 72 horas). Houve diferenças significativas para valores de perda de massa entre os grupos controle e tratamento em ambas as espécies, sendo o grupo tratamento que mais perdeu massa corpórea em todos os períodos, além disso, quase metade dos girinos de P. nattereri morreram em 36 horas de estresse. Não houve diferenças significativas para os dados de desempenho locomotor e volume total entre os grupos testado para girinos de L. fuscus, mas houve diferenças morfometricas significantes nos componentes relacionados a cauda e no volume visceral, onde, o intestino do grupo tratamento foi menor que do controle. Já em P. nattereri, houve diferenças significativas entre os grupos testados para desempenho locomotor, volume total, morfometria da cauda e volume visceral, sendo o estomago e anexo do tratamento maior que do controle. Nossos resultados sugerem que a exposição ao estresse hídrico não afeta significativamente a morfologia e o desempenho locomotor dos girinos de L. fuscus. No entanto, girinos de P. nattereri apresentaram uma sensibilidade ao estresse hídrico prolongado, principalmente sobre o seu desempenho locomotor.

Variabilidade populacional em manguezais: análises moleculares e morfológicas em caranguejos Brachyura (Crustacea: Decapoda)

A análise da estruturação populacional de espécies codistribuídas permite a comparação de padrões de estruturação, fornecendo informações acerca dos fatores que influenciam a diferenciação em espécies pertencentes ao mesmo ecossistema. Este projeto teve como objetivo principal analisar a variabilidade intraespecífica em caranguejos habitantes de manguezais, codistribuídos ao longo do Oceano Atlântico Ocidental, por meio de ferramentas moleculares e morfológicas, visando testar a hipótese de elevada estruturação populacional em manguezais. Para este fim, cinco espécies foram utilizadas como modelo (Aratus pisonii, Goniopsis cruentata, Sesarma rectum, Uca thayeri e Ucides cordatus) e avaliadas por meio de marcadores mitocondriais COI e 16S e nuclear H3 e análises morfológicas comparativas e de morfometria. Os dados moleculares revelaram dois padrões, indicando elevada estruturação populacional para as espécies A. pisonii e U. thayeri e ausência de estruturação para G. cruentata, S. rectum e U. cordatus. Os dados morfológicos, no entanto, não acompanham esses padrões, já que não foram encontradas diferenças morfológicas ou morfométricas associadas aos grupos evidenciados pelas análises moleculares. A ausência de fluxo gênico entre regiões para algumas espécies deve-se, muito provavelmente, à existência de fatores que não se limitam ao isolamento por distância, mas também devido a diferenças na duração do estágio larval e a diferenças bruscas em alguns fatores abióticos, como a salinidade, por exemplo, que, associados às diferentes características do desenvolvimento larval de cada espécie, culminam na existência de estruturas populacionais diferentes. Além disso, os padrões de diferenciação genética observados concordam com os cenários biogeográficos propostos para o Atlântico Ocidental, no qual mudanças e flutuações geológicas, climáticas e oceanográficas, resultantes do fechamento do Istmo do Panamá e de ciclos glaciais na América do Norte, promoveram divergência genética.

Efeito do inibidor de proteinase de origem vegetal EcTI, sobre a inflamação pulmonar alérgica crônica em camundongos Balb/c

INTRODUÇÃO: A prevalência de asma tem crescido e a maioria dos pacientes com asma grave não obtém o controle total dos sintomas com as terapias disponíveis, fazendo-se necessária a busca por novas alternativas terapêuticas. Inibidores de proteinases têm sido estudados como tratamento de processos inflamatórios, dentre eles o Enterolobium contortisiliquum Tripsin Inhibitor (EcTI) OBJETIVO: Avaliar se o inibidor de proteinase EcTI modula a hiperresponsividade brônquica à metacolina, inflamação, remodelamento e estresse oxidativo nas vias aéreas e septos alveolares em um modelo experimental de inflamação pulmonar alérgica crônica. MÉTODOS: Vinte e quatro camundongos Balb/c machos, entre seis e sete semanas de vida, pesando em media 25 g foram divididos em quatro grupos: C (controle), OVA (sensibilizados com ovalbumina, 50 ug intraperironeal (i.p) nos dias 0 e 14 e desafiados nos dias 22, 24, 26, 28); C+EC (controle tratados com EcTI (2 mg/kg/i.p) nos dias 22 a 28); OVA+EC (sensibilizados e desafiados com ovalbumina e também tratados com EcTI (2 mg/kg -i.p) nos dias 22 a 28). No dia 29, foram realizadas realizadas: (i) hiperresponsividade à metacolina e obtidas as respostas máximas de resistência e elastância do sistema respiratório; (ii) análise histopatológica do pulmão para quantificação de eosinófilos, fibras colágenas e elásticas nas vias aéreas (VA) e nos septos alveolares (SA); e (iii) imunohistoquímica para quantificação de células positivas para IFN-y, IL-4, IL-5, IL-13, MMP-9, TIMP-1, TGF-beta, iNOS, NF-kB e fração de volume de isoprostano nas VA e nos SA. Uma semana após o dia 29 foi realizada a técnica de anafilaxia cutanea passiva(PCA) para quantificar IgE e IgG1. A significância foi considerada quando p < 0,05. RESULTADOS: Houve aumento de todos os parâmetros avaliados no grupo OVA em relação ao grupo controle (p < 0,05). Houve atenuação da resposta máxima de Rrs e Ers no grupo OVA+EC comparado as grupo OVA (p < 0,05). O tratamento com EcTI nos animais sensibilizados atenuou o número de eosinófilos, células positivas para IL-4, IL-5, IL-13,IFN-y, iNOS, MMP-9, TIMP-1, NF-kB e TGF-beta e fração de volume de isoprostano, fibras colágenas e elásticas nas vias aéreas e nos séptos alveolares quando comparado ao grupo OVA (p < 0,05).Houve reaçao de PCA nos animais sensibilizados com ovalbumina. CONCLUSÃO: EcTI atenuou a hiperresponsividade brônquica, a inflamação, o remodelamento e o estresse oxidativo nesse modelo experimental de inflamação pulmonar alérgica crônica. Embora sejam necessários mais estudos, esse inibidor pode ser considerado uma futura ferramenta farmacológica para o tratamento de asma

Estudo de alterações estruturais cerebrais em pacientes com esquizofrenia crônica e de primeiro episódio através de imagens por ressonância magnética com morfometria baseada no voxel

Introdução: Embora alterações estruturais cerebrais na esquizofrenia venham sendo repetidamente demonstradas em estudos de ressonância magnética (RM), ainda permanece incerto se tais alterações são estáticas ou progressivas. Enquanto estudos longitudinais são tradicionalmente utilizados na avaliação da questão da progressão, estudos transversais de neuroimagem comparando diretamente pacientes com esquizofrenia crônica e de primeiro episódio a controles saudáveis têm sido bastante raros até o presente. Com o recente interesse em meganálises combinando dados multicêntricos de RM visando-se a maior poder estatístico, o presente estudo multicêntrico de morfometria baseada no voxel (VBM) foi realizado para avaliar os padrões de alterações estruturais cerebrais segundo os diferentes estágios da doença, bem como para avaliar quais (se alguma) dessas alterações se correlacionariam especificamente a moderadores clínicos potenciais, tais como exposição cumulativa a antipsicóticos, tempo de doença e gravidade da doença. Métodos: Selecionou-se uma ampla amostra de pacientes com esquizofrenia (161, sendo 99 crônicos e 62 de primeiro episódio) e controles (151) a partir de quatro estudos prévios de RM (1,5T) realizados na mesma região do Brasil. O processamento e análise das imagens foi realizado usando-se o software Statistical Parametric Mapping (SPM8) com emprego do algoritmo DARTEL (diffeomorphic anatomical registration through exponentiated Lie algebra). Os efeitos de grupo sobre os volumes regionais de substância cinzenta (SC) foram analisados através de comparações voxel-a-voxel por análises de covariância em modelos lineares gerais, inserindo-se, em todas as análises, o volume total de SC, protocolo do scanner, idade e sexo como variáveis de confusão. Por fim, foram realizadas análises de correlação entre os aludidos moderadores clínicos potenciais e os volumes cerebrais globais e regionais. Resultados: Os pacientes com esquizofrenia de primeiro episódio apresentaram reduções volumétricas sutis em comparação aos controles, em um circuito neural circunscrito e identificável apenas em análises SVC (small volume correction) [p < 0.05, com correção family-wise error (FWE)], incluindo a ínsula, estruturas têmporo-límbicas e corpo estriado. Os pacientes crônicos, por outro lado, apresentaram um padrão de alterações extensas comparativamente aos controles, envolvendo os córtices frontais orbitais, superiores e inferiores bilateralmente, córtex frontal médio direito, ambos os córtices cingulados anteriores, ambas as ínsulas, e os córtices temporais superior e médio direitos (p < 0.05, análises whole-brain com correção FWE). Foram encontradas correlações negativas significantes entre exposição cumulativa a antipsicóticos e volumes globais de SC e substância branca nos pacientes com esquizofrenia, embora as correlações com reduções regionais não tenham sido significantes. Detectaram-se, ainda, correlações negativas significantes entre tempo de doença e volumes regionais relativos da ínsula esquerda, córtex cingulado anterior direito e córtices pré-frontais dorsolaterais nas análises SVC para os grupos conjuntos (esquizofrenia crônica e de primeiro episódio). Conclusão: Os achados supracitados indicam que: a) as alterações estruturais associadas com o diagnóstico de esquizofrenia são mais disseminadas na forma crônica em comparação à de primeiro episódio; b) reduções volumétricas regionais em áreas específicas do cérebro podem variar em função do tempo de doença; c) a exposição cumulativa a antipsicóticos associou-se a alterações volumétricas globais, e não regionais

Point clouds of measurements in the Dechen Cave near Iserlohn, Germany

Modeling natural phenomena from 3D information enhances our understanding of the environment. Dense 3D point clouds are increasingly used as highly detailed input datasets. In addition to the capturing techniques of point clouds with LiDAR, low-cost sensors have been released in the last few years providing access to new research fields and facilitating 3D data acquisition for a broader range of applications. This letter presents an analysis of different speleothem features using 3D point clouds acquired with the gaming device Microsoft® Kinect. We compare the Kinect sensor with terrestrial LiDAR reference measurements using the KinFu pipeline for capturing complete 3D objects (< 4m**3). The results demonstrate the suitability of the Kinect to capture flowstone walls and to derive morphometric parameters of cave features. Although the chosen capturing strategy (KinFu) reveals a high correlation (R2=0.92) of stalagmite morphometry along the vertical object axis, a systematic overestimation (22% for radii and 44% for volume) is found. The comparison of flowstone wall datasets predominantly shows low differences (mean of 1 mm with 7 mm standard deviation) of the order of the Kinect depth precision. For both objects the major differences occur at strongly varying and curved surface structures (e.g. with fine concave parts).

Spatial distribution and morphometric analysis of thermokarst lakes and other water bodies : Case study from the sporadic permafrost region, Tavvavuoma, Sweden

Projected air and ground temperatures are expected to be higher in Arctic and sub-Arcticlatitudes and with temperatures already close to the limit where permafrost can exist,resistance against degradation is low. With thawing permafrost, the landscape is modifiedwith depression in which thermokarst lakes emerge. In permafrost soils a considerableamount of soil organic carbon is stored, with the potential of altering climate even furtherif expansion and formation of new thermokarst lakes emerge, as decay releasesgreenhouse gases (C02 and CH4) to the atmosphere. Analyzing the spatial distribution andmorphometry over time of thermokarst lakes and other water bodies, is of importance inaccurately predict carbon budget and feedback mechanisms, as well as to assess futurelandscape layout and these features interaction. Different types of high-spatial resolutionaerial and satellite imageries from 1963, 1975, 2003, 2010 and 2015, were used in bothpre- and post-classification change detection analyses. Using object oriented segmentationin eCognition combined with manual adjustments, resulted in digitalized water bodies>28m2 from which direction of change and morphometric values were extracted. Thequantity of thermokarst lakes and other water bodies was in 1963 n=92, with succeedingyears as a trend decreased in numbers, until 2010-2015 when eleven water bodies wereadded in 2015 (n=74 to n=85). In 1963-2003, area of these water bodies decreased with50 651m2 (189 446-138 795m2) and continued to decrease in 2003-2015 ending at 129337m2. Limnicity decreased from 19.9% in 1963 to 14.6% in 2003 (-5.3%). In 2010 and2015 13.7-13.6%. The late increase in water bodies differs from an earlier hypothesis thatsporadic permafrost regions experience decrease in both area and quantity of thermokarstlakes and water bodies. During 1963-2015, land gain has been in dominance of the ratiobetween the two competing processes of expansion and drainage. In 1963-1975, 55/45%,followed by 90/10% in 1975-2003. After major drainage events, land loss increased to62/38% in 2010-2015. Drainage and infilling rates, calculated for 15 shorelines werevaried across both landscape and parts of shorelines, with in average 0.17/0.15/0.14m/yr.Except for 1963-1975 when rate of change in average was in opposite direction (-0.09m/yr.), likely due to evident expansion of a large thermokarst lake. Using a squaregrid, distribution of water bodies was determined, with an indistinct cluster located in NEand central parts. Especially for water bodies <250m2, which is the dominant area classthroughout 1963-2015 ranging from n=39-51. With a heterogeneous composition of bothsmall and large thermokarst lakes, and with both expansion and drainage altering thelandscape in Tavvavuoma, both positive and negative climate feedback mechanisms are inplay - given that sporadic permafrost still exist.

Patients with neck pain demonstrate reduced electromyographic activity of the deep cervical flexor muscles during performance of the craniocervical flexion test

Study Design. Cross-sectional study. Objective. The present study compared activity of deep and superficial cervical flexor muscles and craniocervical flexion range of motion during a test of craniocervical flexion between 10 patients with chronic neck pain and 10 controls. Summary of Background Data. Individuals with chronic neck pain exhibit reduced performance on a test of craniocervical flexion, and training of this maneuver is effective in management of neck complaints. Although this test is hypothesized to reflect dysfunction of the deep cervical flexor muscles, this has not been tested. Methods. Deep cervical flexor electromyographic activity was recorded with custom electrodes inserted via the nose and fixed by suction to the posterior mucosa of the oropharynx. Surface electrodes were placed over the superficial neck muscles ( sternocleidomastoid and anterior scalene). Root mean square electromyographic amplitude and craniocervical flexion range of motion was measured during five incremental levels of craniocervical flexion in supine. Results. There was a strong linear relation between the electromyographic amplitude of the deep cervical flexor muscles and the incremental stages of the craniocervical flexion test for control and individuals with neck pain ( P = 0.002). However, the amplitude of deep cervical flexor electromyographic activity was less for the group with neck pain than controls, and this difference was significant for the higher increments of the task ( P < 0.05). Although not significant, there was a strong trend for greater sternocleidomastoid and anterior scalene electromyographic activity for the group with neck pain. Conclusions. These data confirm that reduced performance of the craniocervical flexion test is associated with dysfunction of the deep cervical flexor muscles and support the validity of this test for patients with neck pain.

A new method of isometric dynamometry for the craniocervical flexor muscles

Background and Purpose. A new method of dynamometry has been developed to measure the performance of the craniocervical (CC) flexor muscles by recording the torque that these muscles exert on the cranium around the CC junction. This report describes the method, the specifications of the instrument, and the preliminary reliability data. Subjects and Methods. For the reliability study, 20 subjects (12 subjects with a history of neck pain, 8 subjects without a history of neck pain) performed, on 2 occasions, maximal voluntary isometric contraction (MVIC) tests of CC flexion in 3 positions within the range of CC flexion and submaximal sustained tests (20% and 50% of MVIC) in the middle range of CC flexion (craniocervical neutral position). Reliability coefficients were calculated to establish the test-retest reliability of the measurements. Results. The method demonstrated good reliability over 2 sessions in the measurement of MVIC (intraclass correlation coefficient [ICC] =.79-.93, SEM=0.6-1.4 N-m) and in the measurement of steadiness (standard deviation of torque amplitude) of a sustained contraction at 20% of NMC (ICC=.74-.80, SEM=0.01 N-m), but not at 50% of MVIC (ICC=.07-.76, SEM=0.04-0.13 N-m). Discussion and Conclusion. The new dynamometry method appears to have potential clinical application in the measurement of craniocervical flexor muscle performance.

Testicular development of Zebu bulls after chronic treatment with a gonadotropin-releasing hormone agonist

The objective was to compare testis characteristics of Zebu bulls treated with the GnRH agonist, deslorelin, at different times and for different durations during their development. An additional objective was to determine the usefulness of a stain for the transcription factor GATA-binding protein 4 (GATA-4) as a specific marker for Sertoli cell nuclei in cattle. Bulls (54) were allocated to nine groups (n = 6) and received s.c. deslorelin implants as follows: G1 = from birth to 3 mo of age; G2 = from 3 to 6 mo; G3 = from 6 to 9 mo; G4 = from 9 to 12 mo; G5 = from birth to 15 mo; G6 = from 3 to 15 mo; G7 = from 6 to 15 mo; G8 = from 12 to 15 mo; and G9 (control) = no implant. Bulls were castrated at 19 mo of age. Paraffin sections (10 mu m) were subjected to quantitative morphometry and GATA-4 immunohistochemistry. At castration, all bulls in the control group (6/6) had attained puberty (scrotal circumference ! 28 cm), whereas a smaller proportion (P < 0.05) had reached puberty in G2 (2/5) and G6 (1/ 6). Bulls in G2 and G6 also had a lesser (P < 0.05) testis weight compared with the control group. Total volume of seminiferous epithelium and total daily sperm production in G2 and G6 were only half that observed in the control group. Spermatids were observed in less than 50% of seminiferous tubules in G2, G6, and G7 compared with 82% in the control group (P < 0.05). Staining for GATA-4 was specific for and abundant in the Sertoli cell nucleus in both pre- and postpubertal bulls, and no other cell nucleus inside the seminiferous tubule was positive for GATA-4. Total number of Sertoli cells was not affected by treatment (P = 0.45), but nuclear volume was smaller in G2 and G6 (P < 0.05) compared with the control group. In conclusion, treatment of Zebu bulls with deslorelin had no apparent beneficial effect on testis development and delayed puberty when treatment was initiated at 3 mo of age. Staining for GATA-4 was a useful method for identifying and quantifying Sertoli cell nuclei in both pre- and postpubertal bulls.

Evidence of altered prefrontal-thalamic circuitry in schizophrenia: An optimised diffusion MRI study

MRI diffusion tensor imaging (DTI), optimized for measuring the trace of the diffusion tensor, was used to investigate microstructural changes in the brains of 12 individuals with schizophrenia compared with 12 matched control subjects. To control for the effects of anatomic variation between subject groups, all participants' diffusion images were non-linearly registered to standard anatomical space. Significant statistical differences in mean diffusivity (MD) measures between the two groups were determined on a pixel-by-pixel basis, using Gaussian random field theory. We found significantly elevated MD measures within temporal, parietal and prefrontal cortical regions in the schizophrenia group (P > 0.001), especially within the medial frontal gyrus and anterior cingulate. The dorsal medial and anterior nucleus of the thalamus, including the caudate, also exhibited significantly increased MD in the schizophrenia group (P > 0.001). This study has shown for the first time that MD measures offer an alternative strategy for investigating altered prefrontal-thalamic circuitry in schizophrenia. (c) 2006 Elsevier Inc. All rights reserved.

Comorbidity and genotype modify receptor expression in human alcoholics

Chronic alcohol misuse leads to both widespread and localized damage in human cerebral cortex. The latter, as neuronal loss, is marked in superior frontal cortex (SFC) but milder in primary motor cortex (PMC) and elsewhere. Quantitative morphometry by Harper et al showed that neuronal loss is greater in alcoholics with comorbidity (Wernicke Korsakoff syndrome, liver cirrhosis). Previous work revealed a paradox: the marked differences in GABAA receptor density, pharmacology, and expression between alcoholics without cormorbidity and controls are muted or absent in cirrhotic alcoholics. This concurs with work by the Butterworth group on hepatic encephalopathy cases — most of whom had an alcoholic ætiology — who show only minor differences from controls. Glutamate receptor differences are muted in many autopsy studies, though we have evidence that NMDA site pharmacology may vary in cirrhotic alcoholics. Here we used Real-Time PCR normalized to GAPDH deltaCT to quantify NMDA NR1, NR2A and NR2B subunit expression in SFC and PMC samples obtained at autopsy from alcoholics with and without comorbid cirrhosis and matched controls. Overall subunit transcript expression was signifi cantly lower in alcoholic cirrhotics than in either of the other groups (F2,42 = 12.942, P < 0.001). The effect was most marked for the NR1 subunit; males differed from females, particularly in SFC. The data suggest that if excitotoxicity mediates neuronal loss in SFC, it may be implemented differently: passively in uncomplicated alcoholics, by altered GABAergic transmission; actively in cirrhotic alcoholics, by altered glutamatergic transmission. We also subdivided cases on a panel of genetic markers. Different genotypes interacted with NMDA and GABAA pharmacology and expression. Cirrhotic and uncomplicated alcoholics may differ pathogenically because of inherent characteristics in addition to possible neurotoxic sequelæ to the liver damage.

Anatomical correlates of dynamic auditory processing:relationship to literacy during early adolescence

Adults show great variation in their auditory skills, such as being able to discriminate between foreign speech-sounds. Previous research has demonstrated that structural features of auditory cortex can predict auditory abilities; here we are interested in the maturation of 2-Hz frequency-modulation (FM) detection, a task thought to tap into mechanisms underlying language abilities. We hypothesized that an individual's FM threshold will correlate with gray-matter density in left Heschl's gyrus, and that this function-structure relationship will change through adolescence. To test this hypothesis, we collected anatomical magnetic resonance imaging data from participants who were tested and scanned at three time points: at 10, 11.5 and 13 years of age. Participants judged which of two tones contained FM; the modulation depth was adjusted using an adaptive staircase procedure and their threshold was calculated based on the geometric mean of the last eight reversals. Using voxel-based morphometry, we found that FM threshold was significantly correlated with gray-matter density in left Heschl's gyrus at the age of 10 years, but that this correlation weakened with age. While there were no differences between girls and boys at Times 1 and 2, at Time 3 there was a relationship between gray-matter density in left Heschl's gyrus in boys but not in girls. Taken together, our results confirm that the structure of the auditory cortex can predict temporal processing abilities, namely that gray-matter density in left Heschl's gyrus can predict 2-Hz FM detection threshold. This ability is dependent on the processing of sounds changing over time, a skill believed necessary for speech processing. We tested this assumption and found that FM threshold significantly correlated with spelling abilities at Time 1, but that this correlation was found only in boys. This correlation decreased at Time 2, and at Time 3 we found a significant correlation between reading and FM threshold, but again, only in boys. We examined the sex differences in both the imaging and behavioral data taking into account pubertal stages, and found that the correlation between FM threshold and spelling was strongest pre-pubertally, and the correlation between FM threshold and gray-matter density in left Heschl's gyrus was strongest mid-pubertally.