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1.
Cell ; 187(7): 1745-1761.e19, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38518772

RESUMEN

Proprioception tells the brain the state of the body based on distributed sensory neurons. Yet, the principles that govern proprioceptive processing are poorly understood. Here, we employ a task-driven modeling approach to investigate the neural code of proprioceptive neurons in cuneate nucleus (CN) and somatosensory cortex area 2 (S1). We simulated muscle spindle signals through musculoskeletal modeling and generated a large-scale movement repertoire to train neural networks based on 16 hypotheses, each representing different computational goals. We found that the emerging, task-optimized internal representations generalize from synthetic data to predict neural dynamics in CN and S1 of primates. Computational tasks that aim to predict the limb position and velocity were the best at predicting the neural activity in both areas. Since task optimization develops representations that better predict neural activity during active than passive movements, we postulate that neural activity in the CN and S1 is top-down modulated during goal-directed movements.


Asunto(s)
Neuronas , Propiocepción , Animales , Propiocepción/fisiología , Neuronas/fisiología , Encéfalo/fisiología , Movimiento/fisiología , Primates , Redes Neurales de la Computación
2.
Cell ; 184(12): 3242-3255.e10, 2021 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-33979655

RESUMEN

Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta oscillations. Based on studies in rodents, researchers have hypothesized that phase precession may be a general neural pattern for representing sequential events for learning and memory. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal states. Our findings thus extend theta phase precession to humans and suggest that this phenomenon has a broad functional role for the neural representation of both spatial and non-spatial information.


Asunto(s)
Corteza Entorrinal/fisiología , Hipocampo/fisiología , Potenciales de Acción/fisiología , Adulto , Animales , Objetivos , Humanos , Masculino , Neuronas/fisiología , Roedores , Análisis y Desempeño de Tareas , Ritmo Teta/fisiología
3.
Cell ; 171(2): 440-455.e14, 2017 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-28942925

RESUMEN

Corticospinal neurons (CSNs) represent the direct cortical outputs to the spinal cord and play important roles in motor control across different species. However, their organizational principle remains unclear. By using a retrograde labeling system, we defined the requirement of CSNs in the execution of a skilled forelimb food-pellet retrieval task in mice. In vivo imaging of CSN activity during performance revealed the sequential activation of topographically ordered functional ensembles with moderate local mixing. Region-specific manipulations indicate that CSNs from caudal or rostral forelimb area control reaching or grasping, respectively, and both are required in the transitional pronation step. These region-specific CSNs terminate in different spinal levels and locations, therefore preferentially connecting with the premotor neurons of muscles engaged in different steps of the task. Together, our findings suggest that spatially defined groups of CSNs encode different movement modules, providing a logic for parallel-ordered corticospinal circuits to orchestrate multistep motor skills.


Asunto(s)
Médula Cervical/fisiología , Destreza Motora , Vías Nerviosas , Animales , Calcio/análisis , Corteza Cerebral/citología , Corteza Cerebral/fisiología , Médula Cervical/citología , Miembro Anterior/fisiología , Articulaciones/fisiología , Ratones , Ratones Endogámicos C57BL
4.
Proc Natl Acad Sci U S A ; 121(18): e2314224121, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38648482

RESUMEN

Making healthy dietary choices is essential for keeping weight within a normal range. Yet many people struggle with dietary self-control despite good intentions. What distinguishes neural processing in those who succeed or fail to implement healthy eating goals? Does this vary by weight status? To examine these questions, we utilized an analytical framework of gradients that characterize systematic spatial patterns of large-scale neural activity, which have the advantage of considering the entire suite of processes subserving self-control and potential regulatory tactics at the whole-brain level. Using an established laboratory food task capturing brain responses in natural and regulatory conditions (N = 123), we demonstrate that regulatory changes of dietary brain states in the gradient space predict individual differences in dietary success. Better regulators required smaller shifts in brain states to achieve larger goal-consistent changes in dietary behaviors, pointing toward efficient network organization. This pattern was most pronounced in individuals with lower weight status (low-BMI, body mass index) but absent in high-BMI individuals. Consistent with prior work, regulatory goals increased activity in frontoparietal brain circuits. However, this shift in brain states alone did not predict variance in dietary success. Instead, regulatory success emerged from combined changes along multiple gradients, showcasing the interplay of different large-scale brain networks subserving dietary control and possible regulatory strategies. Our results provide insights into how the brain might solve the problem of dietary control: Dietary success may be easier for people who adopt modes of large-scale brain activation that do not require significant reconfigurations across contexts and goals.


Asunto(s)
Índice de Masa Corporal , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Conducta Alimentaria/fisiología , Imagen por Resonancia Magnética , Encéfalo/fisiología , Autocontrol , Corteza Cerebral/fisiología , Dieta
5.
J Neurosci ; 44(29)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886056

RESUMEN

The small G-protein Ras-related C3 botulinum toxin substrate 1 (Rac1) promotes the formation of filamentous actin (F-actin). Actin is a major component of dendritic spines, and we previously found that alcohol alters actin composition and dendritic spine structure in the nucleus accumbens (NAc) and the dorsomedial striatum (DMS). To examine if Rac1 contributes to these alcohol-mediated adaptations, we measured the level of GTP-bound active Rac1 in the striatum of mice following 7 weeks of intermittent access to 20% alcohol. We found that chronic alcohol intake activates Rac1 in the DMS of male mice. In contrast, Rac1 is not activated by alcohol in the NAc and DLS of male mice or in the DMS of female mice. Similarly, closely related small G-proteins are not activated by alcohol in the DMS, and Rac1 activity is not increased in the DMS by moderate alcohol or natural reward. To determine the consequences of alcohol-dependent Rac1 activation in the DMS of male mice, we inhibited endogenous Rac1 by infecting the DMS of mice with an adeno-associated virus (AAV) expressing a dominant negative form of the small G-protein (Rac1-DN). We found that overexpression of AAV-Rac1-DN in the DMS inhibits alcohol-mediated Rac1 signaling and attenuates alcohol-mediated F-actin polymerization, which corresponded with a decrease in dendritic arborization and spine maturation. Finally, we provide evidence to suggest that Rac1 in the DMS plays a role in alcohol-associated goal-directed learning. Together, our data suggest that Rac1 in the DMS plays an important role in alcohol-dependent structural plasticity and aberrant learning.


Asunto(s)
Cuerpo Estriado , Ratones Endogámicos C57BL , Plasticidad Neuronal , Proteína de Unión al GTP rac1 , Animales , Masculino , Ratones , Proteína de Unión al GTP rac1/metabolismo , Proteína de Unión al GTP rac1/genética , Plasticidad Neuronal/fisiología , Plasticidad Neuronal/efectos de los fármacos , Femenino , Cuerpo Estriado/metabolismo , Cuerpo Estriado/efectos de los fármacos , Etanol/farmacología , Aprendizaje/fisiología , Aprendizaje/efectos de los fármacos , Neuropéptidos/metabolismo , Neuropéptidos/genética , Espinas Dendríticas/metabolismo , Espinas Dendríticas/efectos de los fármacos
6.
J Neurosci ; 44(12)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38290848

RESUMEN

The subthalamic nucleus (STN) receives cortical inputs via the hyperdirect and indirect pathways, projects to the output nuclei of the basal ganglia, and plays a critical role in the control of voluntary movements and movement disorders. STN neurons change their activity during execution of movements, while recent studies emphasize STN activity specific to cancelation of movements. To address the relationship between execution and cancelation functions, we examined STN activity in two Japanese monkeys (Macaca fuscata, both sexes) who performed a goal-directed reaching task with a delay that included Go, Cancel, and NoGo trials. We first examined responses to the stimulation of the forelimb regions in the primary motor cortex and/or supplementary motor area. STN neurons with motor cortical inputs were found in the dorsal somatomotor region of the STN. All these STN neurons showed activity changes in Go trials, suggesting their involvement in execution of movements. Part of them exhibited activity changes in Cancel trials and sustained activity during delay periods, suggesting their involvement in cancelation of planed movements and preparation of movements, respectively. The STN neurons rarely showed activity changes in NoGo trials. Go- and Cancel-related activity was selective to the direction of movements, and the selectivity was higher in Cancel trials than in Go trials. Changes in Go- and Cancel-related activity occurred early enough to initiate and cancel movements, respectively. These results suggest that the dorsal somatomotor region of the STN, which receives motor cortical inputs, is involved in preparation and execution of movements and cancelation of planned movements.


Asunto(s)
Corteza Motora , Núcleo Subtalámico , Masculino , Femenino , Animales , Haplorrinos , Núcleo Subtalámico/fisiología , Ganglios Basales , Corteza Motora/fisiología , Neuronas/fisiología
7.
Brain ; 147(6): 2230-2244, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38584499

RESUMEN

Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how this occurs during arbitration between the two systems in obsessive-compulsive disorder. Inspired by a brain model in which the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to examine whether disruptions in the arbitration process via the fronto-striatal circuit would underlie imbalanced decision-making and compulsions in patients. Thirty patients with obsessive-compulsive disorder [mean (standard deviation) age = 26.93 (6.23) years, 12 females (40%)] and 30 healthy controls [mean (standard deviation) age = 24.97 (4.72) years, 17 females (57%)] underwent functional MRI scans while performing the two-step Markov decision task, which was designed to dissociate goal-directed behaviour from habitual behaviour. We employed a neurocomputational model to account for an uncertainty-based arbitration process, in which a prefrontal arbitrator (i.e. inferior frontal gyrus) allocates behavioural control to a more reliable strategy by selectively gating the putamen. We analysed group differences in the neural estimates of uncertainty of each strategy. We also compared the psychophysiological interaction effects of system preference (goal-directed versus habitual) on fronto-striatal coupling between groups. We examined the correlation between compulsivity score and the neural activity and connectivity involved in the arbitration process. The computational model captured the subjects' preferences between the strategies. Compared with healthy controls, patients had a stronger preference for the habitual system (t = -2.88, P = 0.006), which was attributed to a more uncertain goal-directed system (t = 2.72, P = 0.009). Before the allocation of controls, patients exhibited hypoactivity in the inferior frontal gyrus compared with healthy controls when this region tracked the inverse of uncertainty (i.e. reliability) of goal-directed behaviour (P = 0.001, family-wise error rate corrected). When reorienting behaviours to reach specific goals, patients exhibited weaker right ipsilateral ventrolateral prefronto-putamen coupling than healthy controls (P = 0.001, family-wise error rate corrected). This hypoconnectivity was correlated with more severe compulsivity (r = -0.57, P = 0.002). Our findings suggest that the attenuated top-down control of the putamen by the prefrontal arbitrator underlies compulsivity in obsessive-compulsive disorder. Enhancing fronto-striatal connectivity may be a potential neurotherapeutic approach for compulsivity and adaptive decision-making.


Asunto(s)
Toma de Decisiones , Objetivos , Imagen por Resonancia Magnética , Trastorno Obsesivo Compulsivo , Humanos , Femenino , Adulto , Masculino , Imagen por Resonancia Magnética/métodos , Trastorno Obsesivo Compulsivo/fisiopatología , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/psicología , Incertidumbre , Toma de Decisiones/fisiología , Adulto Joven , Modelos Neurológicos , Conducta Compulsiva/fisiopatología , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Putamen/fisiopatología , Putamen/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Simulación por Computador
8.
J Neurophysiol ; 132(4): 1126-1141, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39196679

RESUMEN

Walking in natural environments requires visually guided modifications, which can be more challenging when involving sideways steps rather than longer steps. This exploratory study investigated whether these two types of modifications involve different changes in the central drive to spinal motor neurons of leg muscles. Fifteen adults [age: 36 ± 6 (SD) years] walked on a treadmill (4 km/h) while observing a screen displaying the real-time position of their toes. At the beginning of the swing phase, a visual target appeared in front (forward) or medial-lateral (sideways) of the ground contact in random step cycles (approximately every third step). We measured three-dimensional kinematics and electromyographic activity from leg muscles bilaterally. Intermuscular coherence was calculated in the alpha (5-15 Hz), beta (15-30 Hz), and gamma bands (30-45 Hz) approximately 230 ms before and after ground contact in control and target steps. Results showed that adjustments toward sideways targets were associated with significantly higher error, lower foot lift, and higher cocontraction between antagonist ankle muscles. Movements toward sideways targets were associated with larger beta-band soleus (SOL): medial gastrocnemius (MG) coherence and a more narrow and larger peak of synchronization in the cumulant density before ground contact. In contrast, movements toward forward targets showed no significant differences in coherence or synchronization compared with control steps. Larger SOL:MG beta-band coherence and short-term synchronization were observed during sideways, but not forward, gait modifications. This suggests that visually guided gait modifications may involve differences in the central drive to spinal ankle motor neurons dependent on the level of task difficulty.NEW & NOTEWORTHY This exploratory study suggests a specific and temporally restricted increase of central (likely corticospinal) drive to ankle muscles in relation to visually guided gait modifications. The findings indicate that a high level of visual attention to control the position of the ankle joint precisely before ground contact may involve increased central drive to ankle muscles. These findings are important for understanding the neural mechanisms underlying visually guided gait and may help develop rehabilitation interventions.


Asunto(s)
Marcha , Neuronas Motoras , Músculo Esquelético , Humanos , Adulto , Masculino , Femenino , Músculo Esquelético/fisiología , Neuronas Motoras/fisiología , Marcha/fisiología , Fenómenos Biomecánicos/fisiología , Electromiografía , Percepción Visual/fisiología , Médula Espinal/fisiología , Desempeño Psicomotor/fisiología , Persona de Mediana Edad , Caminata/fisiología , Pierna/fisiología
9.
Eur J Neurosci ; 60(6): 5300-5327, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39161082

RESUMEN

To better understand neural processing during adaptive learning of stimulus-response-reward contingencies, we recorded synchrony of neuronal activity in anterior cingulate cortex (ACC) and hippocampal rhythms in male rats acquiring and switching between spatial and visual discrimination tasks in a Y-maze. ACC population activity as well as single unit activity shifted shortly after task rule changes or just before the rats adopted different task strategies. Hippocampal theta oscillations (associated with memory encoding) modulated an elevated proportion of rule-change responsive neurons (70%), but other neurons that were correlated with strategy-change, strategy value and reward-rate were not. However, hippocampal sharp wave-ripples modulated significantly higher proportions of rule-change, strategy-change and reward-rate responsive cells during post-session sleep but not pre-session sleep. This suggests an underestimated mechanism for hippocampal mismatch and contextual signals to facilitate ACC to detect contingency changes for cognitive flexibility, a function that is attenuated after it is damaged.


Asunto(s)
Giro del Cíngulo , Hipocampo , Neuronas , Ritmo Teta , Animales , Giro del Cíngulo/fisiología , Ritmo Teta/fisiología , Masculino , Hipocampo/fisiología , Neuronas/fisiología , Ratas , Aprendizaje por Laberinto/fisiología , Recompensa , Ratas Long-Evans , Sueño/fisiología
10.
Eur J Neurosci ; 60(4): 4518-4535, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38973167

RESUMEN

The balance between goal-directed and habitual control has been proposed to determine the flexibility of instrumental behaviour, in both humans and animals. This view is supported by neuroscientific studies that have implicated dissociable neural pathways in the ability to flexibly adjust behaviour when outcome values change. A previous Diffusion Tensor Imaging study provided preliminary evidence that flexible instrumental performance depends on the strength of parallel cortico-striatal white-matter pathways previously implicated in goal-directed and habitual control. Specifically, estimated white-matter strength between caudate and ventromedial prefrontal cortex correlated positively with behavioural flexibility, and posterior putamen-premotor cortex connectivity correlated negatively, in line with the notion that these pathways compete for control. However, the sample size of the original study was limited, and so far, there have been no attempts to replicate these findings. In the present study, we aimed to conceptually replicate these findings by testing a large sample of 205 young adults to relate cortico-striatal connectivity to performance on the slips-of-action task. In short, we found only positive neural correlates of goal-directed performance, including striatal connectivity (caudate and anterior putamen) with the dorsolateral prefrontal cortex. However, we failed to provide converging evidence for the existence of a neural habit system that puts limits on the capacity for flexible, goal-directed action. We discuss the implications of our findings for dual-process theories of instrumental action.


Asunto(s)
Cuerpo Estriado , Objetivos , Vías Nerviosas , Sustancia Blanca , Humanos , Sustancia Blanca/fisiología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/anatomía & histología , Masculino , Femenino , Adulto , Cuerpo Estriado/fisiología , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/anatomía & histología , Adulto Joven , Vías Nerviosas/fisiología , Adolescente , Corteza Cerebral/fisiología , Corteza Cerebral/diagnóstico por imagen , Imagen de Difusión Tensora/métodos
11.
Am J Transplant ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38880177

RESUMEN

Delayed graft function (DGF) increases morbidity and mortality in kidney transplant recipients. Operative parameters, including hemodynamic manipulation through vasopressors and fluids, can impact perfusion to the newly transplanted kidney and influence DGF incidence. We analyzed intraoperative time-series data in 5-minute intervals from kidney transplant recipient operations (N = 545) in conjunction with pretransplant characteristics and postsurgical outcomes, including DGF incidence, 60-day creatinine, and graft survival. Of the operations, 127 DGF events were captured in our cohort from a single academic transplant center (57/278 donations after brainstem death [DBDs], 65/150 donations after circulatory/cardiac death [DCDs], 5/117 live donations). In multiple regression, postanastomosis hypotension defined as mean arterial pressure (MAP) <75 mmHg was a risk factor for DGF independent of conventional predictors of DGF in DCD and DBD kidneys. DCD recipients with DGF had lower average postanastomosis MAP (DGF: 80.1 ± 8.1 mmHg vs no DGF: 76.4 ± 6.7 mmHg, P = .004). Interaction analysis demonstrated above-average doses of vasopressors and crystalloids were associated with improved outcomes when used at MAPs ≤75 mmHg, but they were associated with increased DGF at MAPs >75 mmHg, suggesting that the incidence of DGF can be highly influenced by intraoperative hemodynamic controls. This analysis of surgical time courses has identified potential new strategies for goal-directed anesthesia in renal transplantation.

12.
Oncologist ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940449

RESUMEN

BACKGROUND: Given the typical trajectory of glioblastoma, many patients lose decision-making capacity over time, which can lead to inadequate advance care planning (ACP) and end-of-life (EOL) care. We aimed to evaluate patients' current ACP and EOL care status. PATIENTS AND METHODS: We conducted a cohort study on 205 patients referred to oncologists at a Korean tertiary hospital between 2017 and 2022. We collected information on sociodemographic factors, cancer treatment, palliative care consultation, ACP, legal documents on life-sustaining treatment (LST) decisions, and aggressiveness of EOL care. RESULTS: With a median follow-up time of 18.3 months: 159 patients died; median overall survival: 20.3 months. Of the 159 patients, 11 (6.9%) and 63 (39.6%) had advance directive (AD) and LST plans, respectively, whereas 85 (53.5%) had neither. Among the 63 with LST plans, 10 (15.9%) and 53 (84.1%) completed their forms through self-determination and family determination, respectively. Of the 159 patients who died, 102 (64.2%) received palliative care consultation (median time: 44 days from the first consultation to death) and 78 (49.1%) received aggressive EOL care. Those receiving palliative care consultations were less likely to receive aggressive EOL care (83.3% vs 32.4%, P < .001), and more likely to use more than 3 days of hospice care at EOL (19.6% vs 68.0%, P < .001). CONCLUSIONS: The right to self-determination remains poorly protected among patients with glioblastoma, with nearly 90% not self-completing AD or LST plan. As palliative care consultation is associated with less aggressive EOL care and longer use of hospice care, physicians should promptly introduce patients to ACP conversations and palliative care consultations.

13.
Hum Brain Mapp ; 45(10): e26770, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38970217

RESUMEN

Alpha oscillations are known to play a central role in several higher-order cognitive functions, especially selective attention, working memory, semantic memory, and creative thinking. Nonetheless, we still know very little about the role of alpha in the generation of more remote semantic associations, which is key to creative and semantic cognition. Furthermore, it remains unclear how these oscillations are shaped by the intention to "be creative," which is the case in most creativity tasks. We aimed to address these gaps in two experiments. In Experiment 1, we compared alpha oscillatory activity (using a method which distinguishes genuine oscillatory activity from transient events) during the generation of free associations which were more vs. less distant from a given concept. In Experiment 2, we replicated these findings and also compared alpha oscillatory activity when people were generating free associations versus associations with the instruction to be creative (i.e. goal-directed). We found that alpha was consistently higher during the generation of more distant semantic associations, in both experiments. This effect was widespread, involving areas in both left and right hemispheres. Importantly, the instruction to be creative seems to increase alpha phase synchronisation from left to right temporal brain areas, suggesting that intention to be creative changed the flux of information in the brain, likely reflecting an increase in top-down control of semantic search processes. We conclude that goal-directed generation of remote associations relies on top-down mechanisms compared to when associations are freely generated.


Asunto(s)
Ritmo alfa , Creatividad , Objetivos , Semántica , Humanos , Ritmo alfa/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Asociación , Electroencefalografía , Adolescente
14.
Cogn Affect Behav Neurosci ; 24(3): 469-490, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38291308

RESUMEN

Psychological research on human motivation repeatedly observed that approach goals (i.e., goals to attain success) increase task enjoyment and intrinsic motivation more strongly than avoidance goals (i.e., goals to avoid failure). The present study sought to address how the reward network in the brain-including the striatum and ventromedial prefrontal cortex-is involved when individuals engage in the same task with a focus on approach or avoidance goals. Participants reported stronger positive emotions when they focused on approach goals, but stronger anxiety and disappointment when they focused on avoidance goals. The fMRI analyses revealed that the reward network in the brain showed similar levels of activity to cues predictive of approach and avoidance goals. In contrast, the two goal states were associated with different patterns of activity in the visual cortex, hippocampus, and cerebellum during success and failure outcomes. Representation similarity analysis further revealed shared and different representations within the striatum and vmPFC between the approach and avoidance goal states, suggesting both the similarity and uniqueness of the mechanisms behind the two goal states. In addition, the distinct patterns of activation in the striatum were associated with distinct subjective experiences participants reported between the approach and the avoidance conditions. These results suggest the importance of examining the pattern of striatal activity in understanding the mechanisms behind different motivational states in humans.


Asunto(s)
Ansiedad , Mapeo Encefálico , Encéfalo , Objetivos , Imagen por Resonancia Magnética , Motivación , Recompensa , Humanos , Masculino , Femenino , Motivación/fisiología , Adulto Joven , Ansiedad/fisiopatología , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Adulto , Reacción de Prevención/fisiología , Felicidad , Adolescente
15.
Neurobiol Learn Mem ; 211: 107915, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38527649

RESUMEN

Rat autoshaping procedures generate two readily measurable conditioned responses: During lever presentations that have previously signaled food, rats approach the food well (called goal-tracking) and interact with the lever itself (called sign-tracking). We investigated how reinforced and nonreinforced trials affect the overall and temporal distributions of these two responses across 10-second lever presentations. In two experiments, reinforced trials generated more goal-tracking than sign-tracking, and nonreinforced trials resulted in a larger reduction in goal-tracking than sign-tracking. The effect of reinforced trials was evident as an increase in goal-tracking and reduction in sign-tracking across the duration of the lever presentations, and nonreinforced trials resulted in this pattern transiently reversing and then becoming less evident with further training. These dissociations are consistent with a recent elaboration of the Rescorla-Wagner model, HeiDI (Honey, R.C., Dwyer, D.M., & Iliescu, A.F. (2020a). HeiDI: A model for Pavlovian learning and performance with reciprocal associations. Psychological Review, 127, 829-852.), a model in which responses related to the nature of the unconditioned stimulus (e.g., goal-tracking) have a different origin than those related to the nature of the conditioned stimulus (e.g., sign-tracking).


Asunto(s)
Condicionamiento Clásico , Refuerzo en Psicología , Animales , Masculino , Ratas , Condicionamiento Clásico/fisiología , Condicionamiento Operante/fisiología , Objetivos , Conducta Animal/fisiología
16.
Microvasc Res ; 152: 104630, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38048876

RESUMEN

OBJECTIVE: Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid - compared to crystalloid - therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury. METHODS: This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function. RESULTS: Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2-860.1) vs. 595.6 (496.3-694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2-592.1) vs. 442.1 (361.2-523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7-701.8) vs. 548.7 (444.0-653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid - compared to crystalloid - therapy also had less small intestinal, but not renal and hepatic, histopathological damage. CONCLUSIONS: Goal-directed isooncotic hydroxyethyl-starch colloid - compared to balanced isotonic crystalloid - therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.


Asunto(s)
Objetivos , Daño por Reperfusión , Humanos , Animales , Porcinos , Soluciones Cristaloides , Microcirculación , Fluidoterapia/métodos , Derivados de Hidroxietil Almidón/farmacología , Derivados de Hidroxietil Almidón/uso terapéutico , Isquemia/terapia , Coloides/uso terapéutico , Reperfusión , Soluciones Isotónicas/farmacología , Soluciones Isotónicas/uso terapéutico
17.
Transfusion ; 64 Suppl 2: S191-S200, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38566492

RESUMEN

INTRODUCTION: The VCM is a point-of-care analyzer using a new viscoelastometry technique for rapid assessment of hemostasis on fresh whole blood. Its characteristics would make it suitable for use in austere environments. The purpose of this study was to evaluate the VCM in terms of repeatability, reproducibility and interanalyzer correlation, reference values in our population, correlation with standard coagulation assays and platelet count, correlation with the TEG5000 analyzer and resistance to stress conditions mimicking an austere environment. METHODS: Repeatability, reproducibility, and interanalyzer correlation were performed on quality control samples (n = 10). Reference values were determined from blood donor samples (n = 60). Correlations with standard biological assays were assessed from ICU patients (n = 30) and blood donors (n = 60) samples. Correlation with the TEG5000 was assessed from blood donor samples. Evaluation of vibration resistance was performed on blood donor (n = 5) and quality control (n = 5) samples. RESULTS: The CVs for repeatability and reproducibility ranged from 0% to 11%. Interanalyzer correlation found correlation coefficients (r2) ranging from 0.927 to 0.997. Our reference values were consistent with those provided by the manufacturer. No robust correlation was found with conventional coagulation tests. The correlation with the TEG5000 was excellent with r2 ranging from 0.75 to 0.92. Resistance to stress conditions was excellent. CONCLUSION: The VCM analyzer is a reliable, easy-to-use instrument that correlates well with the TEG5000. Despite some logistical constraints, the results suggest that it can be used in austere environments. Further studies are required before its implementation.


Asunto(s)
Sistemas de Atención de Punto , Humanos , Sistemas de Atención de Punto/normas , Reproducibilidad de los Resultados , Valores de Referencia , Tromboelastografía/métodos , Tromboelastografía/instrumentación , Femenino , Masculino , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/instrumentación , Pruebas de Coagulación Sanguínea/normas , Recuento de Plaquetas/métodos , Recuento de Plaquetas/instrumentación , Donantes de Sangre
18.
Horm Behav ; 158: 105468, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38101144

RESUMEN

Hormonal contraceptives are utilized by millions of women worldwide. However, it remains unclear if these powerful endocrine modulators may alter cognitive function. Habit formation involves the progression of instrumental learning as it goes from being a conscious goal-directed process to a cue-driven automatic habitual motor response. Dysregulated goal and/or habit is implicated in numerous psychopathologies, underscoring the relevance of examining the effect of hormonal contraceptives on goal-directed and habitual behavior. This study examined the effect of levonorgestrel (LNG), a widely used progestin-type contraceptive, on the development of habit in intact female rats. Rats were implanted with subcutaneous capsules that slowly released LNG over the course of the experiment or cholesterol-filled capsules. All female rats underwent operant training followed by reward devaluation to test for habit. One group of females was trained at a level that is sub-threshold to habit, while another group of females was trained to a level well over the habit threshold observed in intact females. The results reveal that all sub-threshold trained rats remained goal-directed irrespective of LGN treatment, suggesting LNG is not advancing habit formation in female rats at this level of reinforcement. However, in rats that were overtrained well above the threshold, cholesterol females showed habitual behavior, thus replicating a portion of our original studies. In contrast, LNG-treated habit-trained rats remained goal-directed, indicating that LNG impedes the development and/or expression of habit following this level of supra-threshold to habit training. Thus, LNG may offset habit formation by sustaining attentional or motivational processes during learning in intact female rats. These results may be clinically relevant to women using this type of hormonal contraceptive as well as in other progestin-based hormone therapies.


Asunto(s)
Objetivos , Levonorgestrel , Humanos , Ratas , Femenino , Animales , Levonorgestrel/farmacología , Progestinas/farmacología , Condicionamiento Operante/fisiología , Hábitos , Colesterol/farmacología , Anticonceptivos/farmacología
19.
J Exp Biol ; 227(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38690630

RESUMEN

Desert ants stand out as some of the most intriguing insect navigators, having captured the attention of scientists for decades. This includes the structure of walking trajectories during goal approach and search behaviour for the nest and familiar feeding sites. In the present study, we analysed such trajectories with regard to changes in walking direction. The directional change of the ants was quantified, i.e. an angle θ between trajectory increments of a given arclength λ was computed. This was done for different length scales λ, according to our goal of analysing desert ant path characteristics with respect to length scale. First, varying λ through more than two orders of magnitude demonstrated Brownian motion characteristics typical of the random walk component of search behaviour. Unexpectedly, this random walk component was also present in - supposedly rather linear - approach trajectories. Second, there were small but notable deviations from a uniform angle distribution that is characteristic of random walks. This was true for specific search situations, mostly close to the (virtual) goal position. And third, experience with a feeder position resulted in straighter approaches and more focused searches, which was also true for nest searches, albeit to a lesser extent. Taken together, these results both verify and extend previous studies on desert ant path characteristics. Of particular interest are the ubiquitous Brownian motion signatures and specific deviations thereof close to the goal position, indicative of unexpectedly structured search behaviour.


Asunto(s)
Hormigas , Clima Desértico , Caminata , Animales , Hormigas/fisiología , Caminata/fisiología , Navegación Espacial/fisiología
20.
J Exp Biol ; 227(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38813909

RESUMEN

Desert ants stand out as some of the most intriguing insect navigators, having captured the attention of scientists for decades. This includes the structure of walking trajectories during goal approach and search behaviour for the nest and familiar feeding sites. In the present study, we analysed such trajectories with regard to changes in walking direction. The directional change of the ants was quantified, i.e. an angle θ between trajectory increments of a given arclength λ was computed. This was done for different length scales λ, according to our goal of analysing desert ant path characteristics with respect to length scale. First, varying λ through more than two orders of magnitude demonstrated Brownian motion characteristics typical of the random walk component of search behaviour. Unexpectedly, this random walk component was also present in - supposedly rather linear - approach trajectories. Second, there were small but notable deviations from a uniform angle distribution that is characteristic of random walks. This was true for specific search situations, mostly close to the (virtual) goal position. And third, experience with a feeder position resulted in straighter approaches and more focused searches, which was also true for nest searches, albeit to a lesser extent. Taken together, these results both verify and extend previous studies on desert ant path characteristics. Of particular interest are the ubiquitous Brownian motion signatures and specific deviations thereof close to the goal position, indicative of unexpectedly structured search behaviour.


Asunto(s)
Hormigas , Clima Desértico , Caminata , Animales , Hormigas/fisiología , Caminata/fisiología , Navegación Espacial/fisiología
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