Basal ganglia, drug addiction and the neuroscience of maladaptive habits

The mammalian brain has developed memory systems mediating rigid, yet evolutionarily adaptive patterns of responding to invariant environmental stimuli and internal demands. Such memory systems promote the recall of specific response templates and the execution of inflexible actions to liberate buffering capacity for performing conscious, explicit cognitive processing. The dopamine-innervated neostriatum is central to the ability to learn such consistent associations between stimuli and actions implicitly. Controlled by their outcome when initially learned, actions succumb through iteration to the influence of triggering stimuli and progressively detach themselves from the pleasurable results originally produced, thereby becoming pervasive habits. This might be the case for drug-seeking and drug-taking behaviours, actions learned in part through dopamine-dependent drug-induced reinforcement when the drug is first experienced. With extended drug use, however, drugseeking actions might become conditioned to, and triggered by, specific exteroceptive stimuli and/or affective states, gradually becoming irrepressible forms of responding. We will review neuroanatomical, neuropharmacological and behavioural evidence suggesting that the basal ganglia play a prominent role in the shaping of drug addiction, here regarded as a pathological modification of otherwise adaptive habit learning systems mediated by the basal ganglia.peer-reviewe

Pooled Time Series Modeling Reveals Smoking Habit Memory Pattern

Smoking is a habit that is hard to break because nicotine is highly addictive and smoking behavior is strongly linked to multiple daily activities and routines. Here, we explored the effect of gender, age, day of the week, and previous smoking on the number of cigarettes smoked on any given day. Data consisted of daily records of the number of cigarettes participants smoked over an average period of 84 days. The sample included smokers (36 men and 26 women), aged between 18 and 26 years, who smoked at least five cigarettes a day and had smoked for at least 2 years. A panel data analysis was performed by way of multilevel pooled time series modeling. Smoking on any given day was a function of the number of cigarettes smoked on the previous day, and 2, 7, 14, 21, 28, 35, 42, 49, and 56 days previously, and the day of the week. Neither gender nor age influenced this pattern, with no multilevel effects being detected, thus the behavior of all participants fitted the same smoking model. These novel findings show empirically that smoking behavior is governed by firmly established temporal dependence patterns and inform temporal parameters for the rational design of smoking cessation programs

Complicaciones en el uso de aloinjertos intercalares tras resección de tumores óseos

La reconstrucción ósea mediante aloinjertos intercalares es una técnica de uso frecuente tras resecciones tumorales, que presenta -a largo plazo- mejores resultados que las endoprótesis diafisarias o los autoinjertos vascularizados. Sin embargo, entre las complicaciones más frecuentes destacan las infecciones y las fracturas del aloinjero asociadas a roturas o aflojamientos de la osteosíntesis. Se presentan dos casos tratados con reconstrucciones de este tipo en los que el sistema de osteosíntesis utilizado fracasó, en uno de ellos de forma repetida.The reconstruction of skeletal defects using bone allografts is a frequent procedure after tumoral resections associated to good long-term results, usually better than diaphyseal endoprostheses or autologous grafts. Nevertheless, there are some complications: infection and allograft fracture associated with failure or broken fixation. We report two cases of bone reconstruction in who the fixation failed, twice in one of them

Efectividad de un programa de ahorro de sangre en prótesis total de cadera electiva

En el ámbito de la Cirugía Ortopédica, la implantación de una prótesis total de cadera es uno de los procesos que más frecuentemente requiere reposición hemática en el postoperatorio inmediato. La autodonación preoperatorio se contempla como uno de los procedimientos más eficaces y seguros, aunque no puede llevarse a cabo en todos los pacientes y deben considerarse otras alternativas como los recuperadores de sangre a partir de los drenajes quirúrgicos o el uso pre-operatorio de eritropoyetina. La experiencia de la autodonación en nuestro hospital en el período 1996-2001 ha permitido reducir las necesidades de sangre alogénica en estos pacientes, y ha clarificado el perfil de pacientes que con mayor probabilidad completarán el programa de autodonación y no precisarán sangre alogénica; y, por el contrario, aquellos que serían candidatos a otras técnicas de reposición hematica.In the field of Orthopaedic Surgery, total hip replacement is one of the procedures that most frequently need post operative blood transfusion. Predeposit autologous transfusión is considered a safety an efficient procedure that virtually eliminates the risk of viral transmission and immunological reactions, but this method can not be use in all the patients and other techniques -like intraoperative and postoperative blood salvage, use of epoetin alfa-, must be considered. Our experience with predeposit autologous transfusión from 1996 to 2001 has allowed use to reduce the need of allogenic blood tranfusion. We defined in what patients we can suggests this technique or consider other alternatives

Intensive longitudinal modelling predicts diurnal activity of salivary alpha-amylase

Salivary alpha-amylase (sAA) activity has been widely used in psychological and medical research as a surrogate marker of sympathetic nervous system activation, though its utility remains controversial. The aim of this work was to compare alternative intensive longitudinal models of sAA data: (a) a traditional model, where sAA is a function of hour (hr) and hr squared (sAAj,t = f(hr, hr2 ), and (b) an autoregressive model, where values of sAA are a function of previous values (sAAj,t = f(sAA j,t-1, sAA j,t-2, . . ., sAA j,t-p). Nineteen normal subjects (9 males and 10 females) participated in the experiments and measurements were performed every hr between 9:00 and 21:00 hr. Thus, a total of 13 measurements were obtained per participant. The Napierian logarithm of the enzymatic activity of sAA was analysed. Data showed that a second-order autoregressive (AR(2)) model was more parsimonious and fitted better than the traditional multilevel quadratic model. Therefore, sAA follows a process whereby, to forecast its value at any given time, sAA values one and two hr prior to that time (sAA j,t = f(SAAj,t-1, SAAj,t-2) are most predictive, thus indicating that sAA has its own inertia, with a “memory” of the two previous hr. These novel findings highlight the relevance of intensive longitudinal models in physiological data analysis and have considerable implications for physiological and biobehavioural research involving sAA measurements and other stress-related biomarkers

Box counting dimension of red blood cells samples when filtered with wavelet transform

Automatic recognizing of different populations of several millions of red blood cells (RBCs) is a useful tool in Hematology and Clinical Diagnosis. In this work we studied samples of several millions of RBCs: on one hand healthy control RBCs and on the other hand control RBCs incubated with Trichinella spiralis larval parasites. The alteration on the cells membrane with the parasite can be studied with box-counting dimension on both samples. Previously we applied wavelet transform to all the samples in order to improve the results. The procedure to remove noise from an image is based on the decomposition of the observed signal in a set of wavelets and taking threshold values to select the appropriate coefficients through which the signal can be reconstructed. In our work we compared the results obtained when analyzing the raw signals and the ones obtained after applying wavelet transform, and the results were different and more clearly characterized when the signal were treated with wavelet transform. Finally, the present method using wavelet transform is suitable to optimize the characterization of the RBCs damage when incubated with the larval parasites.Publicado en: Mecánica Computacional vol. XXXV, no. 43Facultad de Ingenierí

Cellular EXchange Imaging (CEXI): Evaluation of a diffusion model including water exchange in cells using numerical phantoms of permeable spheres

Purpose: Biophysical models of diffusion MRI have been developed to characterize microstructure in various tissues, but existing models are not suitable for tissue composed of permeable spherical cells. In this study we introduce Cellular Exchange Imaging (CEXI), a model tailored for permeable spherical cells, and compares its performance to a related Ball \& Sphere (BS) model that neglects permeability. Methods: We generated DW-MRI signals using Monte-Carlo simulations with a PGSE sequence in numerical substrates made of spherical cells and their extracellular space for a range of membrane permeability. From these signals, the properties of the substrates were inferred using both BS and CEXI models. Results: CEXI outperformed the impermeable model by providing more stable estimates cell size and intracellular volume fraction that were diffusion time-independent. Notably, CEXI accurately estimated the exchange time for low to moderate permeability levels previously reported in other studies ($\kappa<25\mu m/s$). However, in highly permeable substrates ($\kappa=50\mu m/s$), the estimated parameters were less stable, particularly the diffusion coefficients. Conclusion: This study highlights the importance of modeling the exchange time to accurately quantify microstructure properties in permeable cellular substrates. Future studies should evaluate CEXI in clinical applications such as lymph nodes, investigate exchange time as a potential biomarker of tumor severity, and develop more appropriate tissue models that account for anisotropic diffusion and highly permeable membranes.Comment: 7 figures, 2 tables, 21 pages, under revie

Preliminary results on the application of the aminoacid racemization technique in the Murcia Region (SE Iberian Peninsula) and their interest in paleoseismological research

Geochronology is a critical issue in paleoseismological research. The aminoacid racemization technique shows important advantages respect to more traditional dating methods; not just for the lower costs and promptness, also because the object to analyze is relatively frequent, in this study: terrestrial gastropods. Furthermore, the costs of the analysis are by far faster and cheaper compared to other dating techniques. Racemization results allow comparing the relative age from different sedimentary units from one trench to another.Additionally, the racemization technique can also be used as a geochronological tool, provided a calibration curve has been first obtained for the particular climate for the area and, ideally, for a particular genus. In this study we show the results obtained from the analysis of 40 samples of terrestrial gastropods from 7 different trenches located in the Murcia Region (SE Spain). Making use of the D/L ratio of aspartic acid we show the coherence found between relative stratigraphic ages and the racemization age. Finally, we show a provisional conversion equation between age of racemization, obtained from Torres et al. (1997) algorithm, and the likely age of the samEl control geocronológico es una cuestión crítica en los estudios de paleosismología. La técnica de racemización de aminoácidos ofrece importantes ventajas respecto a otros métodos de datación, tanto en los costes y rapidez, como en la facilidad de encontrar el objeto de análisis; en este estudio, gasterópodos terrestres. Los resultados permiten comparar la edad relativa entre unidades sedimentarias diferentes de unas zanjas a otras. La técnica de racemización también es una herramienta geocronológica, si bien es necesario primero establecer una curva de calibración para el ambiente climático de la zona e, idealmente, para un género concreto. En este estudio se muestran los resultados obtenidos en 40 muestras de gasterópodos terrestres recogidas en 7 zanjas de investigación paleosismológica en la Región de Murcia. Haciendo uso de la relación D/L del ácido aspártico mostramos la coherencia entre las edades relativas estratigráficas y su edad de racemización. Finalmente, proponemos una relación provisional de conversión entre las edades de racemización obtenidas por el algoritmo de Torres et al. (1997) para gasterópodos de la zona central de la Península Ibérica y la edad probable de las muestra

Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation

Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxietywithout producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin,MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of preclinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here,we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these newtherapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice

Improving prediction of COVID-19 evolution by fusing epidemiological and mobility data

[EN] We are witnessing the dramatic consequences of the COVID¿19 pandemic which, unfortunately, go beyond the impact on the health system. Until herd immunity is achieved with vaccines, the only available mechanisms for controlling the pandemic are quarantines, perimeter closures and social distancing with the aim of reducing mobility. Governments only apply these measures for a reduced period, since they involve the closure of economic activities such as tourism, cultural activities, or nightlife. The main criterion for establishing these measures and planning socioeconomic subsidies is the evolution of infections. However, the collapse of the health system and the unpredictability of human behavior, among others, make it difficult to predict this evolution in the short to medium term. This article evaluates different models for the early prediction of the evolution of the COVID¿19 pandemic to create a decision support system for policy¿makers. We consider a wide branch of models including artificial neural networks such as LSTM and GRU and statistically based models such as autoregressive (AR) or ARIMA. Moreover, several consensus strategies to ensemble all models into one system are proposed to obtain better results in this uncertain environment. Finally, a multivariate model that includes mobility data provided by Google is proposed to better forecast trend changes in the 14¿day CI. A real case study in Spain is evaluated, providing very accurate results for the prediction of 14¿day CI in scenarios with and without trend changes, reaching 0.93 R2, 4.16 RMSE and 1.08 MAE.This work has been partially supported by the Spanish Ministry of Science and Innovation, under Grants RYC2018-025580-I, RTI2018-096384-B-I00, RTC-2017-6389-5 and RTC2019-007159-5, by the Fundacion Seneca del Centro de Coordinacion de la Investigacion de la Region de Murcia under Project 20813/PI/18, by the "Conselleria de Educacion, Investigacion, Cultura y Deporte, Direccio General de Ciencia i Investigacio, Proyectos AICO/2020", Spain, under Grant AICO/2020/302 and a predoctoral contract by the Generalitat Valenciana and the European Social Fund under Grant ACIF/2018/219.García-Cremades, S.; Morales-García, J.; Hernández-Sanjaime, R.; Martínez-España, R.; Bueno-Crespo, A.; Hernández-Orallo, E.; López-Espín, JJ.... (2021). Improving prediction of COVID-19 evolution by fusing epidemiological and mobility data. Scientific Reports. 11(1):1-16. https://doi.org/10.1038/s41598-021-94696-2S11611