John Fredy Ochoa

Emotional processing in Colombian ex-combatants and its relationship with empathy and executive functions

In this work, the neural correlates of emotional processing in Colombian ex-combatants with different empathy profiles were compared to normal controls matched for age, gender and educational level. Forty ex-combatants and 20 non ex-combatants were recruited for this study. Empathy levels as well as executive functions were measured. Empathy level was used to create three groups. Group 1 (G1) included ex-combatants with normal empathy scores, and Group 2 included ex-combatants with low scores on at least one empathy sub-scales. In control group (Ctrl), participants with no antecedents of being combatants and with normal scores in empathy were included. Age, gender, educational and intelligence quotients level were controlled among groups. event-related potentials (ERPs) were recorded while individuals performed an affective picture processing task that included positive, neutral and negative emotional stimuli, which elicit an early modulation of emotion categorization (Early Posterior Negativity (EPN)) and late evaluative process (LPP). EPN differences were found among affective categories, but no group effects were observed at this component. LPP showed a main effect of category and group (higher amplitudes in ex-combatants). There was an inverse correlation between empathy and executive functions scores and ERPs. Results are discussed according to the impact of emotional processing on empathy profile.

Successful object encoding induces increased directed connectivity in presymptomatic early-onset Alzheimer's disease

Background: Recent studies report increases in neural activity in brain regions critical to episodic memory at preclinical stages of Alzheimer’s disease (AD). Although electroencephalography (EEG) is widely used in AD studies, given its non-invasiveness and low cost, there is a need to translate the findings in other neuroimaging methods to EEG. Objective: To examine how the previous findings using functional magnetic resonance imaging (fMRI) at preclinical stage in presenilin-1 E280A mutation carriers could be assessed and extended, using EEG and a connectivity approach. Methods: EEG signals were acquired during resting and encoding in 30 normal cognitive young subjects, from an autosomal dominant early-onset AD kindred from Antioquia, Colombia. Regions of the brain previously reported as hyperactive were used for connectivity analysis. Results: Mutation carriers exhibited increasing connectivity at analyzed regions. Among them, the right precuneus exhibited the highest changes in connectivity. Conclusion: Increased connectivity in hyperactive cerebral regions is seen in individuals, genetically-determined to develop AD, at preclinical stage. The use of a connectivity approach and a widely available neuroimaging technique opens the possibility to increase the use of EEG in early detection of preclinical AD.

Neurophysiological correlates in Mild Cognitive Impairment detected using group Independent Component Analysis.

Alzheimers disease is the most prevalent cause of dementia. Mild Cognitive Impairment (MCI) is defined as a grey area between intact cognitive functioning and clinical dementia. Electroencephalography (EEG) has been used to identify biomarkers in dementia. Currently, there is a great interest in translating the study from raw signals to signal generators, trying to keep the relationship with neurophysiology. In the current study, EEG recordings during an encoding task were acquired in MCI subjects and healthy controls. Data was decomposed using group Independent Component Analysis (gICA) and the most neuronal components were analyzed using Phase Intertrial Coherence (PIC) and Phase shift Intertrial Coherence (PsIC). MCI subjects exhibited an increase of PIC in the theta band, while controls showed increase in PsIC in the alpha band. Correlation between PIC and PsIC and clinical scales were also found. Those findings indicate that the methodology proposed based in gICA can help to extract information from EEG recordings with neurophysiological meaning.

Effective Connectivity Changes in Presymptomatic Alzheimer’s Disease with E280A Presenilin-1 Mutation Gene

Alzheimer’s disease (AD) is the most prevalent cause of dementia generally with an onset after the 65 years. However, there are some genetic mutations that induce the onset of the neurocognitive symptoms before that age. The study of mutation carriers provides a unique opportunity to identify early preclinical changes related to AD. The Electroencephalography is a powerful tool for the identification of predictive markers of cognitive deterioration since it enables investigate the electrical pattern affected early in the neurodegenerative processes. In the current work two groups, mutation carriers and non-carriers, perform a memory encoding task during Electroencephalography recording. Brain Graphs are built using the directed Direct Transfer. Our results point to an increase of connectivity in mutation carriers in the theta and alpha1 bands. Given that the changes are in bands typically related to memory tasks the increases could be associated to compensatory mechanism to the neurodegenerative process.

Automation of bioinformatic tools to detect gene fusion events in the Leishmania braziliensis and Leishmania major genomes

This work tried to identify gene fusion events in the genome of Leishmania major and Leishmania braziliensis based on computational processes using bioinformatics tools, designing and implementing a protocol that allowed the automation in the identification process. The project was justified in the actual need to find therapeutic targets to generate new alternative treatment for leishmaniasis. Methodologically, the paper uses comparative genomics tools using two databases, FusionDB and Domain Fusion. The fused genes of these two databases were aligned against the complete genomes of both species of Leishmania implementing the Inparanoid algorithm with a 50% value of coverage. A total of 75 possible gene fusion events, 41 were duplication events after the speciation of organisms, 4 were bifunctional genes and the rest were false positives. These results served to check the validity of the method, giving clues about the nature of gene fusion events in Leishmania and serve the community to use the computer protocol as a tool that can be applied or extrapolated to other microorganisms.

Precuneus failures in subjects of the PSEN1 E280A family at risk of developing Alzheimer's disease detected using quantitative electroencephalography

BACKGROUND Presenilin-1 (PSEN1) mutations are the most common cause of familial early onset Alzheimers disease (AD). The PSEN1 E280A (E280A) mutation has an autosomal dominant inheritance and is involved in the production of amyloid-β. The largest family group of carriers with E280A mutation is found in Antioquia, Colombia. The study of mutation carriers provides a unique opportunity to identify brain changes in stages previous to AD. Electroencephalography (EEG) is a low cost and minimally invasiveness technique that enables the following of brain changes in AD. OBJECTIVE To examine how previous reported differences in EEG for Theta and Alpha-2 rhythms in E280A subjects are related to specific regions in cortex and could be tracked across different ages. METHODS EEG signals were acquired during resting state from non-carriers and carriers, asymptomatic and symptomatic subjects from E280A kindred from Antioquia, Colombia. Independent component analysis (ICA) and inverse solution methods were used to locate brain regions related to differences in Theta and Alpha-2 bands. RESULTS ICA identified two components, mainly related to the Precuneus, where the differences in Theta and Alpha-2 exist simultaneously at asymptomatic and symptomatic stages. When the ratio between Theta and Alpha-2 is used, significant correlations exist with age and a composite cognitive scale. CONCLUSION Theta and Alpha-2 rhythms are altered in E280A subjects. The alterations are possible to track at Precuneus regions using EEG, ICA, and inverse solution methods.

Algorithm for simulation of craniotomies assisted by peripheral for 3D virtual navigation

Neurosurgical procedures require high precision and an accurate localization of the structures. For that reason and due to the advances in 3D visualization, the software for planning and training neurosurgeries has become an important tool for neurosurgeons and students, but the manipulation of the 3D structures is not always easy for the staff that usually works with 2D images. This paper describes a system developed in open source software that allows performing a virtual craniotomy (a common procedure in neurosurgery that enables the access to intracranial lesions) in 3D slicer; the system includes a peripheral input in order to permit the manipulation of the 3D structures according to camera movements and to guide the movement of the craniotomy tool.

Conectividad funcional en un paciente con alucinaciones complejas. Un caso de autoscopia

Autoscopy, from Greek autos (self) and skopeo (looking at), are complex hallucinations wherein the patient feels a visual duplication of his body. The current paper presents some brain connectivity correlates, obtained from resting state functional magnetic resonance, in a patient with refractory epilepsy who suffers autoscopic hallucinations during her seizures. Introduce the functional neuroimaging findings in a patient with autoscopic hallucinations. As part of the evaluation protocol for patients with refractory epilepsy, electroencephalographic video monitoring, positron emission tomography and resting state functional magnetic resonance imaging, were done to a patient that suffers autoscopic hallucinations during her crisis. The information obtained from those studies are correlated with clinical information. In the patient, the positron emision tomography and the electroencephalographic video monitoring study indicate an injury in the right occipital lobe, findings that coincide with previous literature report about autoscopy. The neuronal synchronization, measured by functional resonance, is abnormal in the same region where is altered the positron emision tomography imaging, enabling to relate the autoscopy phenomena with brain connectivity alterations. The patient has clinical features of autoscopic hallucination. MRI indicates areas with altered brain dynamics in the case of the patient coincide with regions reported in the literature. This study provides evidence on the role of neuronal synchronization mechanisms and the perception of hallucinations.

Alzheimer’s Disease: Initial Clinical Implementation of Automated Volumetry

Alzheimer’s disease (AD) is a chronic, progressive, and degenerative brain disease. Mild cognitive impairment (MCI) may represent a transitional predementia state between normal aging and AD dementia. Noninvasive diagnostic methods are necessary to identify asymptomatic individuals and MCI subjects with high-risk genetic factors who are candidates for early preventive or therapeutic intervention. Structural MRI methods allow visualization of macroscopic cerebral atrophy secondary to AD cellular changes. To be a diagnostic biomarker, MRI should be able to detect and quantify essential characteristics in high-risk patients (e.g., amnestic MCI individuals or asymptomatic carriers of a high-risk genetic factor with familial AD history) and in patients with clinical AD diagnosis. It is also important to accurately differentiate between healthy control (HC) subjects and AD dementia andMCI individuals. Manually defined MRI regions of interest or automated methods can be used to identify AD and MCI individuals. Image analysis algorithms have allowed the development of MRI-based tools to quantify atrophy in various anatomical regions by automatic segmentation. In 2009, Desikan and colleagues described the use of an automated volumetry tool for AD diagnosis with excellent clinical and neuropsychological correlation (specificity, 91%; sensitivity, 90%). Our goal was to explore the possible implementation of this tool and its usefulness in patients with clinical and neuropsychological diagnosis of MCI and AD dementia.

CHANGES IN BRAIN NETWORK MEASURES IN PRE-SYMPTOMATIC ALZHEIMER'S DISEASE WITH E280A PRESENILIN-1 MUTATION GENE

Autophagy is deregulated in AD and we have recently shown deregulation of autophagy in schizophrenia. Furthermore, ADNP transcripts were increased in lymphocyted from schizophrenia patients compared to matched controls (Molecular Psychiatry, 2013, [Epub ahead of print]). The aim of the present project was to evaluate ADNP and the related ADNP2 lymphocyte expression in AD. Methods: Peripheral lymphocytes were isolated from AD patients and age-matched controls by ficoll grandiet separation. RNA was extracted using the Trizol reagent followed by reverse transcription and quantitative real time polymerase chain reaction (PCR) for ADNP and ADNP2 RNA. Results were normalize to the TATA box transcript. Results: ADNP RNAwas increased by w8-folds in AD lymphocyte samples compared to controls (p<0.05). This was in contrast to the transcript of ADNP2, which did not change. In comparison to schizophrenia patients (Molecular Psychiatry, 2013, [Epub ahead of print]), the increase in ADNP expression was apparently w3-fold greater in AD patients, and ADNP2 expression was also significantly increased in schizophrenia patients. Conclusions: Our results posit ADNP and ADNP2 lymphocyte expression as markers for AD and schizophrenia with differential disregulated expression in the two indications. Interestingly, previous proteomic studies identified ADNP as the only protein decreasing in AD serum, suggesting potential rapid turn-over, structural changes and/or defective translation mechanism that have been associated with cognitive deficiencies. These studies pave the path to better disease understanding, novel biomarkers and personalized medicine.