Childhood adversity modulates structural brain changes in borderline personality but not in major depression disorder.

Adverse childhood experiences (ACEs) negatively affect the function and structure of emotion brain circuits, increasing the risk of various psychiatric disorders. It is unclear if ACEs show disorder specificity with respect to their effects on brain structure. We aimed to investigate whether the structural brain effects of ACEs differ between patients with major depression (MDD) and borderline personality disorder (BPD). These disorders share many symptoms but likely have different etiologies. To achieve our goal, we obtained structural 3T-MRI images from 20 healthy controls (HC), 19 MDD patients, and 18 BPD patients, and measured cortical thickness and subcortical gray matter volumes. We utilized the Adverse Childhood Experiences (ACE) questionnaire to quantify self-reported exposure to childhood trauma. Our findings suggest that individuals with MDD exhibit a smaller cortical thickness when compared to those with BPD. However, ACEs showed a significantly affected relationship with cortical thickness in BPD but not in MDD. ACEs were found to be associated with thinning in cortical regions involved in emotional behavior in BPD, whereas HC showed an opposite association. Our results suggest a potential mechanism of ACE effects on psychopathology involving changes in brain structure. These findings highlight the importance of early detection and intervention strategies.

Recording physiological history of cells with chemical labeling.

Recordings of the physiological history of cells provide insights into biological processes, yet obtaining such recordings is a challenge. To address this, we introduce a method to record transient cellular events for later analysis. We designed proteins that become labeled in the presence of both a specific cellular activity and a fluorescent substrate. The recording period is set by the presence of the substrate, whereas the cellular activity controls the degree of the labeling. The use of distinguishable substrates enabled the recording of successive periods of activity. We recorded protein-protein interactions, G protein-coupled receptor activation, and increases in intracellular calcium. Recordings of elevated calcium levels allowed selections of cells from heterogeneous populations for transcriptomic analysis and tracking of neuronal activities in flies and zebrafish.

Neurodevelopment and early pharmacological interventions in Fragile X Syndrome.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder and the leading monogenic cause of autism and intellectual disability. For years, several efforts have been made to develop an effective therapeutic approach to phenotypically rescue patients from the disorder, with some even advancing to late phases of clinical trials. Unfortunately, none of these attempts have completely succeeded, bringing urgency to further expand and refocus research on FXS therapeutics. FXS arises at early stages of postnatal development due to the mutation and transcriptional silencing of the Fragile X Messenger Ribonucleoprotein 1 gene (FMR1) and consequent loss of the Fragile X Messenger Ribonucleoprotein (FMRP) expression. Importantly, FMRP expression is critical for the normal adult nervous system function, particularly during specific windows of embryogenic and early postnatal development. Cellular proliferation, migration, morphology, axonal guidance, synapse formation, and in general, neuronal network establishment and maturation are abnormally regulated in FXS, underlying the cognitive and behavioral phenotypes of the disorder. In this review, we highlight the relevance of therapeutically intervening during critical time points of development, such as early postnatal periods in infants and young children and discuss past and current clinical trials in FXS and their potential to specifically target those periods. We also discuss potential benefits, limitations, and disadvantages of these pharmacological tools based on preclinical and clinical research.

Abnormal brain network community structure related to psychological stress in schizophrenia.

Recent functional imaging studies in schizophrenia consistently report a disruption of brain connectivity. However, most of these studies analyze the brain connectivity during resting state. Since psychological stress is a major factor for the emergence of psychotic symptoms, we sought to characterize the brain connectivity reconfiguration induced by stress in schizophrenia. We tested the hypothesis that an alteration of the brain's integration-segregation dynamic could be the result of patients with schizophrenia facing psychological stress. To this end, we studied the modular organization and the reconfiguration of networks induced by a stress paradigm in forty subjects (twenty patients and twenty controls), thus analyzing the dynamics of the brain in terms of integration and segregation processes by using 3T-fMRI. Patients with schizophrenia did not show statistically significant differences during the control task compared with controls, but they showed an abnormal community structure during stress condition and an under-connected reconfiguration network with a reduction of hub nodes, suggesting a deficit of integration dynamic with a greater compromise of the right hemisphere. These results provide evidence that schizophrenia has a normal response to undemanding stimuli but shows a disruption of brain functional connectivity between key regions involved in stress response, potentially leading to altered functional brain dynamics by reducing integration capacity and showing deficits recruiting right hemisphere regions. This could in turn underlie the hyper-sensitivity to stress characteristic of schizophrenia.

Heterogeneous CaMKII-Dependent Synaptic Compensations in CA1 Pyramidal Neurons From Acute Hippocampal Slices.

Prolonged changes in neural activity trigger homeostatic synaptic plasticity (HSP) allowing neuronal networks to operate within functional ranges. Cell-wide or input-specific adaptations can be induced by pharmacological or genetic manipulations of activity, and by sensory deprivation. Reactive functional changes caused by deafferentation may partially share mechanisms with HSP. Acute hippocampal slices are a suitable model to investigate relatively rapid (hours) modifications occurring after denervation and explore the underlying mechanisms. As during slicing many afferents are cut, we conducted whole-cell recordings of miniature excitatory postsynaptic currents (mEPSCs) in CA1 pyramidal neurons to evaluate changes over the following 12 h. As Schaffer collaterals constitute a major glutamatergic input to these neurons, we also dissected CA3. We observed an average increment in mEPSCs amplitude and a decrease in decay time, suggesting synaptic AMPA receptor upregulation and subunit content modifications. Sorting mEPSC by rise time, a correlate of synapse location along dendrites, revealed amplitude raises at two separate domains. A specific frequency increase was observed in the same domains and was accompanied by a global, unspecific raise. Amplitude and frequency increments were lower at sites initially more active, consistent with local compensatory processes. Transient preincubation with a specific Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor either blocked or occluded amplitude and frequency upregulation in different synapse populations. Results are consistent with the concurrent development of different known CaMKII-dependent HSP processes. Our observations support that deafferentation causes rapid and diverse compensations resembling classical slow forms of adaptation to inactivity. These results may contribute to understand fast-developing homeostatic or pathological events after brain injury.

Caries dental y determinantes sociales de salud en niños de establecimientos educativos de los distritos de Canchaque y San Miguel de El Faique, provincia de Huancabamba, región de Piura, Perú, 2019 / Dental caries and social determinants of health in children of educational establishments of Canchaque and San Miguel de El Faique districts, Huancabamba province, Piura region, Perú, 2019

RESUMEN Introducción: el objetivo fue determinar la asociación entre Caries Dental (CD) y los Determinantes Sociales de la salud (DSS) en niños de establecimientos educativos de los distritos de Canchaque y San Miguel de El Faique, provincia de Huancabamba, región de Piura, Perú, año 2019. Métodos: estudio transversal. Muestra no probabilística, seleccionando 124 individuos de 11-12 años de sexto grado de primaria y primer grado de secundaria de las escuelas de los distritos de Canchaque y San Miguel de El Faique. Los DSS estuvieron compuestos por: género, ingreso económico, nivel de educación, condición de vivienda, empleo, saneamiento ambiental y acceso a los servicios de salud. La experiencia de CD fue medida mediante el índice CPOD. Se realizó un análisis bivariado empleando las pruebas estadísticas Chi cuadrado, U de Mann Whitney y Kruskal Wallis. Resultados: se encontró asociación entre prevalencia de caries dental y condición de vivienda (p<0,05), el índice de CPOD con género, nivel educativo, servicio higiénico y seguro de salud (p<0,05), y el índice ceod no presentó ninguna asociación con las variables (p>0,05). Conclusión: la caries dental tuvo asociación con los determinantes sociales de la salud de condición de vivienda, género, nivel educativo, servicio higiénico y seguro de salud.

ABSTRAC Introduction: the objective was to determine the association between Dental Caries (DC) and the Social Determinants of Health (SDOH) in children from educational establishments in the Canchaque and San Miguel de El Faique districts, Huancabamba province, Piura region, Peru, 2019. Methods: cross-sectional study. Non-probability sample, selecting 124 individuals from 11-12 years of sixth grade of primary and first grade of secondary from schools in the districts of Canchaque and San Miguel de El Faique, Huancabamba province, Piura-Peru, year 2019. The SDOH were made up of: gender, economic income, education level, housing condition, employment, environmental sanitation and access to health services. DC experience was measured using the DMFT Index. A bivariate analysis was performed using statistical tests Chi-Square, Mann Whitney U test y Kruskal Wallis Results: it was found association between to the prevalence of DC and housing condition (p<0.05), the DMFT index with gender, education level, hygienic service and health insurance (p<0.05), and dmft index there was no association with the variables (p >0.05). Conclusions: the dental caries was associated with SDOH of housing condition, gender, education level, environmental sanitation and health insurance.

Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, cause autosomal recessive dystonia.

Dystonia is a debilitating hyperkinetic movement disorder, which can be transmitted as a monogenic trait. Here, we describe homozygous frameshift, nonsense, and missense variants in TSPOAP1, which encodes the active-zone RIM-binding protein 1 (RIMBP1), as a genetic cause of autosomal recessive dystonia in 7 subjects from 3 unrelated families. Subjects carrying loss-of-function variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy. Conversely, subjects carrying a pathogenic missense variant (p.Gly1808Ser) presented with isolated adult-onset focal dystonia. In mice, complete loss of RIMBP1, known to reduce neurotransmission, led to motor abnormalities reminiscent of dystonia, decreased Purkinje cell dendritic arborization, and reduced numbers of cerebellar synapses. In vitro analysis of the p.Gly1808Ser variant showed larger spike-evoked calcium transients and enhanced neurotransmission, suggesting that RIMBP1-linked dystonia can be caused by either reduced or enhanced rates of spike-evoked release in relevant neural networks. Our findings establish a direct link between dysfunction of the presynaptic active zone and dystonia and highlight the critical role played by well-balanced neurotransmission in motor control and disease pathogenesis.

White matter fiber density abnormalities in cognitively normal adults at risk for late-onset Alzheimer's disease.

Tau accumulation affecting white matter tracts is an early neuropathological feature of late-onset Alzheimer's disease (LOAD). There is a need to ascertain methods for the detection of early LOAD features to help with disease prevention efforts. The microstructure of these tracts and anatomical brain connectivity can be assessed by analyzing diffusion MRI (dMRI) data. Considering that family history increases the risk of developing LOAD, we explored the microstructure of white matter through dMRI in 23 cognitively normal adults who are offspring of patients with Late-Onset Alzheimer's Disease (O-LOAD) and 22 control subjects (CS) without family history of AD. We also evaluated the relation of white matter microstructure metrics with cortical thickness, volumetry, in vivo amyloid deposition (with the help of PiB positron emission tomography -PiB-PET) and regional brain metabolism (as FDG-PET) measures. Finally we studied the association between cognitive performance and white matter microstructure metrics. O-LOAD exhibited lower fiber density and fractional anisotropy in the posterior portion of the corpus callosum and right fornix when compared to CS. Among O-LOAD, reduced fiber density was associated with lower amyloid deposition in the right hippocampus, and greater cortical thickness in the left precuneus, while higher mean diffusivity was related with greater cortical thickness of the right superior temporal gyrus. Additionally, compromised white matter microstructure was associated with poorer semantic fluency. In conclusion, white matter microstructure metrics may reveal early differences in O-LOAD by virtue of parental history of the disorder, when compared to CS without a family history of LOAD. We demonstrate that these differences are associated with lower fiber density in the posterior portion of the corpus callosum and the right fornix.

Author Correction: Retrieval of retrained and reconsolidated memories are associated with a distinct neural network.

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Retrieval of retrained and reconsolidated memories are associated with a distinct neural network.

Consolidated memories can persist from a single day to years, and persistence is improved by retraining or retrieval-mediated plasticity. One retrieval-based way to strengthen memory is the reconsolidation process. Strengthening occurs simply by the presentation of specific cues associated with the original learning. This enhancement function has a fundamental role in the maintenance of memory relevance in animals everyday life. In the present study, we made a step forward in the identification of brain correlates imprinted by the reconsolidation process studying the long-term neural consequences when the strengthened memory is stable again. To reach such a goal, we compared the retention of paired-associate memories that went through retraining process or were labilizated-reconsolidated. Using functional magnetic resonance imaging (fMRI), we studied the specific areas activated during retrieval and analyzed the functional connectivity of the whole brain associated with the event-related design. We used Graph Theory tools to analyze the global features of the network. We show that reconsolidated memories imprint a more locally efficient network that is better at exchanging information, compared with memories that were retrained or untreated. For the first time, we report a method to elucidate the neural footprints associated with a relevant function of memory reconsolidation.

Differential Left Hippocampal Activation during Retrieval with Different Types of Reminders: An fMRI Study of the Reconsolidation Process.

Consolidated memories return to a labile state after the presentation of cues (reminders) associated with acquisition, followed by a period of stabilization (reconsolidation). However not all cues are equally effective in initiating the process, unpredictable cues triggered it, predictable cues do not. We hypothesize that the different effects observed by the different reminder types on memory labilization-reconsolidation depend on a differential neural involvement during reminder presentation. To test it, we developed a declarative task and compared the efficacy of three reminder types in triggering the process in humans (Experiment 1). Finally, we compared the brain activation patterns between the different conditions using functional magnetic resonance imaging (fMRI) (Experiment 2). We confirmed that the unpredictable reminder is the most effective in initiating the labilization-reconsolidation process. Furthermore, only under this condition there was differential left hippocampal activation during its presentation. We suggest that the left hippocampus is detecting the incongruence between actual and past events and allows the memory to be updated.

Inclusión de técnicas imagenológicas en la planificación neuroquirúrgica: integración de equipos multidisciplinarios / Inclusion of imaging techniques in neurosurgical planning: integration of multidisciplinary teams

Introducción: El tratamiento quirúrgico de las epilepsias consiste en lograr la resección del área lesional o epileptógena minimizando a la vez el déficit neurológico postquirúrgico. Las neuroimágenes se han constituido en una poderosa herramienta diagnóstica. El procesamiento de las mismas logran proveer relación topográfica entre la lesión, el área epileptogénica primaria y las áreas funcionales importantes de manera no invasiva. Objetivos: Estudiar la utilidad de incluir diferentes técnicas de imágenes en la evaluación prequirúrgica, planificación y resección quirúrgica de epilepsias. Materiales y Métodos: Se estudiaron 8 pacientes con diagnóstico de epilepsia con diversas técnicas imagenológicas, en resonador 3T y en tomógrafo helicoidal de 64 canales. Las imágenes fueron post-procesadas, corregistradas, fusionadas e incorporadas en el sistema de neuronavegación. La información resultante fue estudiada por un equipo multidisciplinario de físicos médicos y neurocirujanos. Resultados: Los casos presentados muestran que la incorporación e integración de las técnicas de imágenes facilitan la comprensión anatómica, metabólica y funcional del área lesional /epileptogénica y el tejido circundante. La cirugía guiada por imágenes colabora en la mejora de las limitaciones de los métodos “gold standard”, como son la electrocorticografía y la estimulación cortical eléctrica directa, disminuyendo la invasividad, el tamaño de la craneotomía, aumentando el área de resección de la lesión y brindando mayor seguridad en los resultados postquirúrgicos.