Cortico-thalamocortical interactions for learning, memory and decision-making

This is the final version. Available on open access from Wiley via the DOI in this recordThe thalamus and cortex are interconnected both functionally and anatomically and share a common developmental trajectory. Interactions between the mediodorsal thalamus (MD) and different parts of the prefrontal cortex are essential in cognitive processes, such as learning and adaptive decision-making. Cortico-thalamocortical interactions involving other dorsal thalamic nuclei, including the anterior thalamus and pulvinar, also influence these cognitive processes. Our work, and that of others, indicates a crucial influence of these interdependent cortico-thalamocortical neural networks that contributes actively to the processing of information within the cortex. Each of these thalamic nuclei also receives potent subcortical inputs that are likely to provide additional influences on their regulation of cortical activity. Here, we highlight our current neuroscientific research aimed at establishing when cortico-MD thalamocortical neural network communication is vital within the context of a rapid learning and memory discrimination task. We are collecting evidence of MD-prefrontal cortex neural network communication in awake, behaving male rhesus macaques. Given the prevailing evidence, further studies are needed to identify both broad and specific mechanisms that govern how the MD, anterior thalamus and pulvinar cortico-thalamocortical interactions support learning, memory and decision-making. Current evidence shows that the MD (and the anterior thalamus) are crucial for frontotemporal communication, and the pulvinar is crucial for frontoparietal communication. Such work is crucial to advance our understanding of the neuroanatomical and physiological bases of these brain functions in humans. In turn, this might offer avenues to develop effective treatment strategies to improve the cognitive deficits often observed in many debilitating neurological disorders and diseases and in neurodegeneration.Wellcome Trus

Human Cytomegalovirus: detection of congenital and perinatal infection in Argentina

BACKGROUND: Human cytomegalovirus (CMV) is one of the most commonly found agents of congenital infections. Primary maternal infection is associated with risk of symptomatic congenital diseases, and high morbidity is frequently associated with very low birth weight. Neonates with asymptomatic infection develop various sequelae during infancy. This is the first Argentine study performed in neonates with congenital and postnatal HCMV infection. The purpose of this study was to evaluate the performance of the polymerase chain reaction (PCR) technique with different pairs of primers, to detect cytomegalovirus isolated in tissue cultures and directly in urine and dried blood spot (DBS) specimens. Results were compared with IgM detection. METHODS: The study was performed between 1999 and 2001 on routine samples in the Laboratory. A total of 61 urine and 56 serum samples were selected from 61 newborns/infants, 33 patients whose samples were analyzed during the first two to three weeks of life were considered congenital infections; the remaining 28 patients whose samples were taken later than the third week were grouped as perinatal infections, although only in 4 the perinatal transmission of infection was determined unequivocally Cytomegalovirus diagnosis was made by isolating the virus from urine samples in human foreskin fibroblast cells. Three different primer pairs directed to IE, LA and gB genes were used for the HCMV PCR assay in viral isolates. Subsequently, PCR and nested PCR (nPCR) assays with gB primers were performed directly in urine and in 11 samples of dried blood spot (DBS) on Guthrie Card, these results were then compared with serology. RESULTS: The main clinical manifestations of the 33 patients with congenital infection were purpura, jaundice, hepatomegaly and anaemia. Three patients presented low birth weight as single symptom, 10, intracranial calcifications, and 2, kidney failure. In the 28 patients grouped as with perinatal infection, anaemia, hepatosplenomegaly and enzymatic alteration were predominant, and 4 patients were HIV positive. The primers used to amplify the gB region had a PCR positivity rate of 100%, whereas those that amplified IE and LA regions had a PCR positivity rate of 54% and 61% respectively, in CMV isolates. Amplification by PCR of urine samples (with no previous DNA extraction), using primers for the gB region, detected 34/61 positive samples. Out of the 33 samples from patients with congenital infection, 24 (73%) were positive. When nPCR was used in these samples, all were positive, whereas in the remaining 28 patients, two negative cases were found. Cytomegalovirus DNA detection in 11 samples was also carried out in DBS: 7 DBS samples were positive and 4 were negative. CONCLUSIONS: Primers directed to the gB fragment region were the best choice for the detection of CMV DNA in positive isolates. In congenital infections, direct PCR in urine was positive in a high percentage (73%) of samples; however, in patients grouped as with perinatal infection only 36% of the cases were positive. With n-PCR, total sample positivity reached 97%. PCR technique performed in DBS allowed identifying congenital infection in four patients and to be confirmed in 3. These results show the value of nPCR for the detection of all cases of CMV infection. The assay offers the advantage that it may be performed within the normal working day and provides reliable results in a much shorter time frame than that required for either traditional tissue culture or the shell-viral assay

Diagnostic accuracy of consensus diagnostic criteria for frontotemporal dementia in a memory clinic population

Background/Aims: The goal of the present study was to evaluate the diagnostic accuracy of the core diagnostic criteria for frontotemporal dementia (FTD) [Neary D, et al: Neurology 1998;51:1546-1554] within a memory clinic population. Methods: The 5 core diagnostic criteria for FTD were operationalised in an informant-based written questionnaire. For a diagnosis of FTD the total clinical picture was weighted with findings on additional investigations and possible exclusion criteria, with follow-up of at least 1 year. Results: The operationalised core criteria for FTD had a sensitivity of 79% (95% CI = 57-92) and a specificity of 90% (95% CI = 85-94). Conclusion: The core diagnostic criteria for FTD applied in a caregiver questionnaire have good diagnostic accuracy among subjects without advanced dementia attending a memory clinic. This stresses the importance of the informant-based history in the differential diagnosis of dementia. Copyrigh

Desenvolvimento de instrumento para medida dos fatores psicossociais determinantes do comportamento de atividade física em coronariopatas

Este estudo teve como objetivo apresentar o desenvolvimento, a análise de conteúdo e da confiabilidade do Questionário para identificação dos fatores psicossociais determinantes do comportamento de atividade física em coronariopatas, baseado na extensão da Teoria do Comportamento Planejado. O instrumento foi submetido à validade de conteúdo, com realização de sua avaliação por três juízes e pré-teste com cinco sujeitos, até mostrar-se conceitualmente adequado e compreensível aos sujeitos entrevistados. Foi aplicado em 51 sujeitos para a avaliação preliminar da consistência interna, por meio da determinação do coeficiente alfa de Crombach. Foram observados coeficientes alfa de Crombach >0,75 para os constructos Intenção, Atitude, Norma Subjetiva, Autoeficácia e Hábito. O instrumento desenvolvido mostrou evidências de validade de conteúdo e de confiabilidade.Este estudio tuvo como objetivo presentar el desarrollo, el análisis de contenido y de confiabilidad del Cuestionario para la identificación de los factores psicosociales determinantes del comportamiento de actividad física en pacientes afectados de coronariopatías, basado en la extensión de la Teoría del Comportamiento Planificado. Se sometió la validez del contenido del instrumento a la evaluación por parte de tres jueces y pre test con cinco sujetos, hasta mostrarse conceptualmente adecuado y comprensible para los sujetos entrevistados. Fue aplicado en 51 sujetos para la evaluación preliminar de consistencia interna, a través de la determinación del coeficiente Alfa de Cronbach. Fueron observados coeficientes Alfa de Cronbach >0,75 para los constructos Intención, Actitud, Norma Subjetiva, Autoeficacia y Hábito. El instrumento desarrollado evidenció la validez de su contenido, así como su confiabilidad.The aim of this study was to report the development and the analysis of content validity and reliability of the Psychosocial Determinants of Physical Activity among Coronary Heart Disease Patients Questionnaire, based on an extension of the Theory of Planned Behavior. In the content validity step, three experts evaluated the instrument which was, afterwards, pre-tested with five subjects in order to obtain a conceptually appropriate and easily understood instrument. Fifty-one patients participated in the evaluation of internal consistency of the reviewed instrument. Cronbach's alpha coefficients above 0.75 were observed for the constructs: Intention, Attitude, Subjective Norm, Self-efficacy and Habit. The new instrument demonstrated acceptable evidence of content validity and reliability

Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a clinically, genetically and pathologically heterogeneous disorder. Within FTLD with ubiquitin-positive inclusions (FTLD-U), a new pathological subtype named FTLD-FUS was recently found with fused in sarcoma (FUS) positive, TDP-43-negative inclusions, and striking atrophy of the caudate nucleus. The aim of this study was to determine the frequency of FTLD-FUS in our pathological FTLD series, and to describe the clinical, neuroimaging and neuropathological features of FTLD-FUS, especially caudate atrophy. Demographic and clinical data collected prospectively from 387 patients with frontotemporal dementia (FTD) yielded 74 brain specimens. Immunostaining was carried out using a panel of antibodies, including AT-8, ubiquitin, p62, FUS, and TDP-43. Cortical and caudate atrophy on MRI (n = 136) was rated as normal, mild-moderate or severe. Of the 37 FTLD-U cases, 33 were reclassified as FTLD-TDP and four (0.11, 95%: 0.00–0.21) as FTLD-FUS, with ubiquitin and FUS-positive, p62 and TDP-43-negative neuronal intranuclear inclusions (NII). All four FTLD-FUS cases had a negative family history, behavioural variant FTD (bvFTD), and three had an age at onset ≤40 years. MRI revealed mild-moderate or severe caudate atrophy in all, with a mean duration from onset till MRI of 63 months (range 16–119 months). In our total clinical FTD cohort, we found 11 patients (0.03; 95% CI: 0.01–0.05) with bvFTD, negative family history, and age at onset ≤40 years. Caudate atrophy was present in 10 out of 136 MRIs, and included all four FUS-cases. The newly identified FTLD-FUS has a frequency of 11% in FTLD-U, and an estimated frequency of three percent in our clinical FTD cohort. The existence of this pathological subtype can be predicted with reasonable certainty by age at onset ≤40 years, negative family history, bvFTD and caudate atrophy on MRI

Validation of persuasive messages for the promotion of physical activity among people with coronary heart disease

OBJECTIVE: to validate the content of persuasive messages for promoting walking among patients with coronary heart disease (CHD). The messages were constructed to strengthen or change patients' attitudes to walking. METHOD: the selection of persuasive arguments was based on behavioral beliefs (determinants of attitude) related to walking. The messages were constructed based in the Elaboration Likelihood Model and were submitted to content validation. RESULTS: the data was analyzed with the content validity index and by the importance which the patients attributed to the messages' persuasive arguments. Positive behavioral beliefs (i.e. positive and negative reinforcement) and self-efficacy were the appeals which the patients considered important. The messages with validation evidence will be tested in an intervention study for the promotion of the practice of physical activity among patients with CHD.OBJETIVO: validar el contenido de mensajes persuasivos para promover la caminata entre pacientes con enfermedad arterial coronaria (DAC). Los mensajes fueron construidos objetivando al fortalecimiento/cambio de la actitud del paciente con relación a la caminata. MÉTODO: la selección de los argumentos persuasivos fue basada en las creencias comportamentales (determinantes de la actitud) relacionadas a la caminata. Los mensajes fueron construidos con base en el Modelo de Probabilidad de Elaboración y sometidos a la validez de contenido. RESULTADOS: los datos fueron analizados por medio del índice de validez de contenido y por la importancia atribuida por los pacientes a los argumentos persuasivos de los mensajes. Las creencias comportamentales positivas (ejemplo: refuerzo positivo y negativo) y la autoeficacia fueron los reclamos considerados importantes por los pacientes. Los mensajes con evidencias de validación serán testadas en estudio de intervención para promoción de la práctica de actividad física entre pacientes con DAC.OBJETIVO: validar o conteúdo de mensagens persuasivas para promover a caminhada entre pacientes com doença arterial coronária (DAC). As mensagens foram construídas com vistas ao fortalecimento/mudança da atitude do paciente em relação à caminhada. MÉTODO: a seleção dos argumentos persuasivos foi baseada nas crenças comportamentais (determinantes da atitude), relacionadas à caminhada. As mensagens foram construídas com base no Modelo de Probabilidade de Elaboração e submetidas à validade de conteúdo. RESULTADOS: os dados foram analisados por meio do índice de validade de conteúdo e pela importância atribuída pelos pacientes aos argumentos persuasivos das mensagens. As crenças comportamentais positivas (i.e. reforço positivo e negativo) e a autoeficácia foram os apelos considerados importantes pelos pacientes. As mensagens com evidências de validação serão testadas em estudo de intervenção para promoção da prática de atividade física entre pacientes com DAC

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

Higher-order multipole amplitudes in charmonium radiative transitions

Using 24 million $\psi' \equiv \psi(2S)$ decays in CLEO-c, we have searched for higher multipole admixtures in electric-dipole-dominated radiative transitions in charmonia. We find good agreement between our data and theoretical predictions for magnetic quadrupole (M2) amplitudes in the transitions $\psi' \to \gamma \chi_{c1,2}$ and $\chi_{c1,2} \to \gamma J/\psi$, in striking contrast to some previous measurements. Let $b_2^J$ and $a_2^J$ denote the normalized M2 amplitudes in the respective aforementioned decays, where the superscript $J$ refers to the angular momentum of the $\chi_{cJ}$. By performing unbinned maximum likelihood fits to full five-parameter angular distributions, we determine the ratios $a_2^{J=1}/a_2^{J=2} = 0.67^{+0.19}_{-0.13}$ and $a_2^{J=1}/b_2^{J=1} = -2.27^{+0.57}_{-0.99}$, where the theoretical predictions are independent of the charmed quark magnetic moment and are $a_2^{J=1}/a_2^{J=2} = 0.676 \pm 0.071$ and $a_2^{J=1}/b_2^{J=1} = -2.27 \pm 0.16$.Comment: 32 pages, 7 figures, acceptance updat

The development and validation of an urbanicity scale in a multi-country study

Background : Although urban residence is consistently identified as one of the primary correlates of non-communicable disease in low- and middle-income countries, it is not clear why or how urban settings predispose individuals and populations to non-communicable disease (NCD), or how this relationship could be modified to slow the spread of NCD. The urban–rural dichotomy used in most population health research lacks the nuance and specificity necessary to understand the complex relationship between urbanicity and NCD risk. Previous studies have developed and validated quantitative tools to measure urbanicity continuously along several dimensions but all have been isolated to a single country. The purposes of this study were 1) To assess the feasibility and validity of a multi-country urbanicity scale; 2) To report some of the considerations that arise in applying such a scale in different countries; and, 3) To assess how this scale compares with previously validated scales of urbanicity. Methods : Household and community-level data from the Young Lives longitudinal study of childhood poverty in 59 communities in Ethiopia, India and Peru collected in 2006/2007 were used. Household-level data include parents’ occupations and education level, household possessions and access to resources. Community-level data include population size, availability of health facilities and types of roads. Variables were selected for inclusion in the urbanicity scale based on inspection of the data and a review of literature on urbanicity and health. Seven domains were constructed within the scale: Population Size, Economic Activity, Built Environment, Communication, Education, Diversity and Health Services. Results : The scale ranged from 11 to 61 (mean 35) with significant between country differences in mean urbanicity; Ethiopia (30.7), India (33.2), Peru (39.4). Construct validity was supported by factor analysis and high corrected item-scale correlations suggest good internal consistency. High agreement was observed between this scale and a dichotomized version of the urbanicity scale (Kappa 0.76; Spearman’s rank-correlation coefficient 0.84 (p < 0.0001). Linear regression of socioeconomic indicators on the urbanicity scale supported construct validity in all three countries (p < 0.05). Conclusions : This study demonstrates and validates a robust multidimensional, multi-country urbanicity scale. It is an important step on the path to creating a tool to assess complex processes like urbanization. This scale provides the means to understand which elements of urbanization have the greatest impact on health

Search for D0 to p e- and D0 to pbar e+

Using data recorded by CLEO-c detector at CESR, we search for simultaneous baryon and lepton number violating decays of the D^0 meson, specifically, D^0 --> p-bar e^+, D^0-bar --> p-bar e^+, D^0 --> p e^- and D^0-bar --> p e^-. We set the following branching fraction upper limits: D^0 --> p-bar e^+ (D^0-bar --> p-bar e^+) p e^- (D^0-bar --> p e^-) < 1.2 * 10^{-5}, both at 90% confidence level.Comment: 10 pages, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PRD. Comments: changed abstract, added reference for section 1, vertical axis in Fig.5 changed (starts from 1.5 rather than 2.0), fixed typo