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- ItemTheta modulation of hippocampal activity during distinct brain states(2025) Caneo Contreras, Mauricio Andrés; Fuentealba, Pablo; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas; Pontificia Universidad Católica de Chile. Facultad de Ciencias Sociales; Pontificia Universidad Católica de Chile. Facultad de Química y Farmacia; Pontificia Universidad Católica de Chile. Facultad de MedicinaTheta oscillations in the brain play a pivotal role in coordinating behavior across different states. We characterized how distinct brain states (wakefulness and sleep) modulate theta oscillations and associated neural activity in the hippocampus (CA1d and DG) and subcortical regions (SuM, LS, and HyP). Using electrophysiological recordings, we found that theta power and frequency in CA1d and SuM are significantly higher during active exploration (AE) compared to REM sleep. Functional connectivity, evaluated through phase coherence, revealed increased synchrony between CA1d-SuM and SuM-DG pairs during AE. Spike activity exhibited higher firing rates during AE and quiet wakefulness (QW) compared to REM sleep, with stronger spike-theta coupling observed in REM sleep. Additionally, changes in theta power in CA1d, DG, LS, and HyP correlated with speed and acceleration during AE, indicating that these oscillations dynamically reflect locomotor parameters. Our findings underscore how theta oscillations and neural activity adapt to different brain states to support sensorimotor integration and cognitive functions.
- ItemMind wandering: Investigating the role of low-frequency oscillations and cortical connectivity with intracranial human recordings(2025) Herrero Silva, Joaquín Alfonso; Aboitiz, Francisco; Pontificia Universidad Católica de Chile. Facultad de Medicina; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas; Pontificia Universidad Católica de Chile. Facultad de Química y Farmacias; Pontificia Universidad Católica de Chile. Facultad de Ciencias SocialesMind wandering (MW) is a mental state characterized by attentional decoupling from external stimuli and ongoing tasks. At the neural level, MW has been associated with a decrease in the power of high-frequency oscillations in both the ventral and dorsal attentional networks (VAN and DAN). Concurrently, there is an increase in power within the Default Mode Network (DMN). However, contradictory evidence exists regarding the role of low-frequency oscillations in the neural dynamics underlying the emergence of MW. It has been suggested that changes in the power of theta and alpha frequency bands occur simultaneously with attentional decoupling, potentially facilitating its regulation. Moreover, while low-frequency bands are pertinent to the emergence of high-frequency oscillations, the specifics of their cortical distribution during the onset of MW remain uncertain. Additionally, homeostatic variations related to the inhibitory/excitatory balance within attentional networks and the DMN have yet to be adequately described. Therefore, our aim is to elucidate the neural signature associated with low-frequency oscillations that differentiate selective attention from MW. To achieve our objectives, we present the results from nine epileptic patients with electrocortical recordings (ECoG) who were candidates for surgical intervention. Participants completed a modified Sustained Attention to Response Task (SART), previously developed by our team (Henríquez et al., 2016) , to evaluate attentional states classified as sustained attention (ON state), somnolence (SL state), and MW conditions (OFF state). As anticipated, we observed a high proportion of ON responses (78.9%) compared to OFF (12.4%) and SL responses (8.7%). Furthermore, we found that behavioral variability, calculated across four trials preceding questions, increased before OFF responses. This behavioral variability supports the hypothesis that attentional lapses may unfold several seconds prior to thought sampling questions (TSQ). To understand the oscillatory contributions leading to OFF states, we characterized the electrodes of each participant within their respective networks of interest (VAN, DAN, and DMN). We then conducted spectral analysis of each independent electrode to identify differences in brain activity between the ON and OFF states. During OFF states, we observed a decrease in low-frequency power during both spontaneous and time-evoked windows, with non-specific network patterns. Simultaneously, we noted a decrease in aperiodic components that weredriven solely by the DMN. Connectivity dynamics at low frequencies were found to be heightened within the DMN and between the VAN and DAN. Finally, we linked behavioral data with ongoing brain activity to discern how cortical activity influences spontaneous attentional cycling. We found a significant correlation between behavioral variability and the instantaneous phase of theta oscillations immediately prior to trial onset, but only for OFF responses. Consequently, OFF states appear to be influenced by the phase consistency of the trial start. Overall, during mind wandering, we have documented changes in low_x0002_frequency oscillations that presumably guide inhibitory processes in the parietotemporal areas beyond the DMN. Thus, the inhibitory/excitatory balance at a large-scale cortical level is crucial during shifts in attentional fluctuations.
- ItemAsociación entre Obesidad Pregestacional y el Fenotipo de Monocitos y Células Progenitoras Hematopoyéticas Fetales: rol de la Endotoxemia Metabólica(2024) Lepez Rivera Macarena Paz; Casanello Toledo, Paola Cecilia; Pontificia Universidad Católica de Chile. Escuela de MedicinaLa obesidad pregestacional representa un importante desafío de salud pública por su asociación con un estado inflamatorio crónico y endotoxemia metabólica, caracterizada por niveles elevados de lipopolisacáridos (LPS) en sangre. Este entorno adverso durante la gestación puede afectar tanto a la madre como al desarrollo inmunológico del feto. Estudios previos han evidenciado que los hijos de mujeres con obesidad pregestacional presentan una mayor susceptibilidad a infecciones y alteraciones inmunológicas en monocitos al nacer, en comparación con hijos de mujeres normopeso. Dado que los monocitos poseen una vida media corta, se planteó que las alteraciones inmunes podrían originarse en las células progenitoras hematopoyéticas (HPCs), las cuales residen en la médula ósea y son responsables de la generación de células inmunes a lo largo de la vida.Este estudio tuvo como objetivo evaluar de forma integral la relación entre obesidad pregestacional y alteraciones inmunes innatas en recién nacidos, utilizando como referencia a hijos de mujeres con normopeso. Se analizaron la endotoxemia metabólica y las características fenotípicas, funcionales y epigenéticas de monocitos y HPCs en sangre de cordón umbilical.Se reclutaron mujeres embarazadas con obesidad pregestacional y normopeso (n=21 por grupo) en los hospitales Clínico UC-Christus y Sótero del Río, bajo aprobación ética (#200920001). En el momento del parto, se obtuvieron muestras de sangre materna y de cordón para cuantificar niveles de LPS (por fotometría), caracterizar subpoblaciones celulares (citometría de flujo), y evaluar expresión génica (RT-qPCR), metilación global del ADN (EPIC 850K array) y metilación específica del gen PPARγ (pirosecuenciación). Se analizó además la respuesta inmune de monocitos y HPCs tras estimulación con LPS y bloqueo del receptor TLR4.Los resultados mostraron un aumento significativo de LPS en sangre materna y fetal en el grupo con obesidad pregestacional. En los recién nacidos de este grupo, se observó un aumento en la proporción de HPCs mieloides tempranas, monocitos con mayor expresión de genes proinflamatorios (IL-6, IL-1β, MCP1) y una reducción en la expresión de PPARγ. Además, se detectó hipometilación global del ADN en monocitos y un aumento específico del 2% en la metilación del gen PPARγ tanto en monocitos como en HPCs. La estimulación con LPS reveló una respuesta inmune atenuada, con menor expresión de citoquinas (IL-6, MCP1, IL-10) y menor producción de IL-6. El bloqueo de TLR4 inhibió significativamente esta producción.En conclusión, la obesidad pregestacional se asocia con alteraciones inmunológicas en los recién nacidos, mediadas por endotoxemia metabólica y reprogramación epigenética de células hematopoyéticas. Estos hallazgos subrayan la importancia de la salud metabólica materna y el valor de los marcadores epigenéticos como predictores tempranos de riesgo inmunológico y metabólico en la descendencia.
- ItemRole of endothelial dysfunction on tolerance to supine position in patients with acute respiratory distress syndrome on mechanical ventilation(2024) Bachmann Barron, Maria Consuelo; Retamal Montes, Jaime Alejandro; Pontificia Universidad Católica de Chile . Facultad de MedicinaIntroduction: The prone position is a maneuver frequently used to improve oxygenation inpatients with ARDS on mechanical ventilation. Physiologically, optimization of gas exchangeoccurs by recruiting the dorsal regions of the lung, improving the ventilation/perfusion (V/Q)ratio. Despite the benefits, this position presents complications. Therefore, it is important toclearly know its indications and duration time. Prolonged use of the prone position (more than16 hours) can be associated with severe muscle weakness among other complications, whileits use for short and repeated periods is associated with accidents, increase workload, and agreater number of days in IMV. Therefore, it is important to be able to precisely determine themoment in which the patient is ready to be supinated.Through EIT it has been shown that both in healthy and ARDS conditions, the distribution ofpulmonary ventilation is predominantly dorsal in prone, and ventral in supine position. Whileperfusion under normal and pathological conditions presents a dorsal predominance. Itwould be expected that, with adequate endothelial function, the presence of hypoxicpulmonary vasoconstriction allows the redistribution of pulmonary perfusion towardsnormally aerated regions, allowing optimal gas exchange. We hypothesized thatmechanically ventilated in prone position ARDS patients, with endothelial dysfunction are notcapable of regulate pulmonary perfusion and, therefore, increasing their V/Q imbalance, withthe position change worsening oxygenation.Methods: Observational quasi-experimental clinical study in patients admitted to the ICU ofthe UC-CHRISTUS Clinical Hospital, in Santiago, Chile. Patients with diagnosis of ARDSconnected to IMV in prone position were included. Endothelial function was assessed atbaseline through flow-mediated vasodilation and NIRS. Hemodynamic and ventilatoryparameters, ABG, and distribution of ventilation and perfusion through EIT were evaluated inprone and supine for analysis of shunt, dead space, and V/Q mismatch. Lung aeration wasevaluated with lung ultrasound and computed tomography. Supine position intolerance wasdefined as the need for a second prone cycle within the first 24 hours after the switch.Results: This analysis included 20 patients, of whom 13 tolerated the change in position. Nocorrelation was found between the V/Q ratio and tolerance to position change. There werealso no associations found between clinical (NIRS and FMD) and biochemical (bloodmarkers) assessments of endothelial dysfunction and V/Q ratio imbalance. However, othervariables were shown to play a relevant role in tolerance outcomes. The failed group exhibiteda more widespread distribution of lung injury assessed by CT compared to the successfulgroup (local injury). Additionally, the failed group showed significantly higher values of drivingpressure and PaCO2 than the successful group, and these differences were found during boththe prone and supine periods.Conclusions: No relation was observed between tolerance to position change and thepresence of endothelial dysfunction, and we have not been able to find the existence ofpredictive patterns of tolerance. Respiratory mechanics and pulmonary injury distributioncould be the determining factor.
- ItemNeural dynamics of Epistemic Curiosity and Memory(2024) Illesca Matus, Ricardo Sebastián; Rodríguez B., Eugenio; Pontificia Universidad Católica de Chile. Facultad de MedicinaLa curiosidad epistémica es un estado motivacional intrínsecamente gratificante, caracterizado por el deseo de adquirir conocimiento dentro del contexto de incertidumbre, el cual ha sido asociado con el aprendizaje y memoria. Estudios anteriores han vinculado los estados motivacionales y el control cognitivo en contextos inciertos con un aumento del poder de la actividad cerebral oscilatoria theta (3-7 hz) especialmente en áreas frontales. Aún se desconoce si la actividad theta diferencia entre estados altos y bajos de curiosidad epistémica y su papel en el aprendizaje. Para aclarar este asunto, investigamos la actividad oscilatoria asociada con la curiosidad epistémica. Los participantes calificaron su nivel de curiosidad en respuesta a preguntas presentadas en una tarea de trivia mientras se registraba su actividad oscilatoria a través de un electroencefalograma. Posteriormente se les realizó una tarea de recuerdo libre en donde debían escribir todas las respuestas que recordaban de la tarea de trivia. Descubrimos que los estados de alta curiosidad epistémica se asociaron con un aumento significativo en el poder de la actividad theta, en contraste con el ligero aumento en el poder de la actividad theta observado durante los estados de baja curiosidad epistémica. Además, los estados de alta curiosidad epistémica se asociaron con un mayor recuerdo de respuestas en comparación con los estados de baja curiosidad epistémica. Concluimos que la actividad theta proporciona información sobre los mecanismos neuronales subyacentes a la curiosidad epistémica. Nuestros hallazgos sugieren que el aumento en el poder theta puede reflejar el control cognitivo en estados gratificantes de incertidumbre, como la curiosidad epistémica. Además, estos mecanismos también podrían subyacer en los efectos de los estados de alta curiosidad epistémica en el recuerdo de información de interés.