Dentate gyrus is needed for memory retrieval.

The hippocampus is crucial for acquiring and retrieving episodic and contextual memories. In previous studies, the inactivation of dentate gyrus (DG) neurons by chemogenetic- and optogenetic-mediated hyperpolarization led to opposing conclusions about DG's role in memory retrieval. One study used Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-mediated clozapine N-oxide (CNO)-induced hyperpolarization and reported that the previously formed memory was erased, thus concluding that denate gyrus is needed for memory maintenance. The other study used optogenetic with halorhodopsin induced hyperpolarization and reported and dentate gyrus is needed for memory retrieval. We hypothesized that this apparent discrepancy could be due to the length of hyperpolarization in previous studies; minutes by optogenetics and several hours by DREADD/CNO. Since hyperpolarization interferes with anterograde and retrograde neuronal signaling, it is possible that the memory engram in the dentate gyrus and the entorhinal to hippocampus trisynaptic circuit was erased by long-term, but not with short-term hyperpolarization. We developed and applied an advanced chemogenetic technology to selectively silence synaptic output by blocking neurotransmitter release without hyperpolarizing DG neurons to explore this apparent discrepancy. We performed in vivo electrophysiology during trace eyeblink in a rabbit model of associative learning. Our work shows that the DG output is required for memory retrieval. Based on previous and recent findings, we propose that the actively functional anterograde and retrograde neuronal signaling is necessary to preserve synaptic memory engrams along the entorhinal cortex to the hippocampal trisynaptic circuit.

Point of care thoracic ultrasound versus chest computed tomography in the approach of febrile neutropenia patients: A diagnostic accuracy cohort study.

Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study. Consecutive patients with febrile neutropenia who underwent CT (Computerized Tomography) underwent TUS evaluation within 24h of CT. Both studies were performed by an expert who was blinded to the clinical information and results of the alternative imaging modalities. 34 patients met the inclusion criteria. The median age was 39.9 years (±17 standard deviation). TUS as a diagnostic test had a sensitivity of 92.9% and specificity of 83.3%, negative predictive value of 71.4%, and positive predictive value of 96.3%. Substantial between-method agreement was demonstrated with a kappa of 0.71 (P = .001) between the TUS and chest CT findings. We obtained a kappa of 1 (P = .001) for the final diagnosis of Pleural Effusion (PE). We concluded that TUS is a promising screening test for immunocompromised individuals. The results showed good diagnostic performance of TUS compared to CT for the detection of pulmonary findings highly suggestive of pathology with high accuracy and reproducibility.

Effect of Propranolol on Motor Cortex Excitability in Essential Tremor: An Exploratory Study.

Background: Essential tremor, the world's most prevalent movement disorder, lacks a clear understanding of its pathophysiology. Propranolol, a non-specific beta-blocker capable of crossing the blood-brain barrier, is a primary choice for essential tremor treatment. While its tremor-reducing effects are generally attributed to peripheral actions, various uses hint at central adrenergic effects. Nevertheless, propranolol's precise impact on the central nervous system in essential tremor subjects remains unexplored. Methods: In this study, we employed transcranial magnetic stimulation to assess the influence of propranolol on the excitability of the primary motor cortex (M1) in patients with essential tremor, compared to an age- and sex-matched control group. Cortical excitability parameters were measured following placebo and propranolol administration, encompassing resting and active motor thresholds, motor evoked potential characteristics, cortical silent period, and the input/output curve. Results: Distinct effects were observed across the two cortical hemispheres. Essential tremor patients displayed inhibition of the left M1 cortex and heightened excitability in the right M1 cortex four hours after propranolol administration, but not following placebo. Conclusions: These findings suggest potential differential noradrenergic excitatory and inhibitory modulation. However, comprehensive understanding necessitates further investigations, including left-handed participants and more diverse essential tremor subpopulations. This study underscores the need for continued exploration to unravel propranolol's complex effects on motor cortex excitability in essential tremor.

Directional uncertainty in chase and escape dynamics.

Intercepting and avoiding collisions with moving targets are crucial skills for survival. However, little is known about how these behaviors are implemented when the trajectory of the moving target introduces variability and ambiguity into the perceptual-motor system. We developed a simple visuomotor task in which participants used a joystick to interact with a computer-controlled dot that moved along two-dimensional trajectories. This virtual system allowed us to define the role of the moving object (predator or prey) and adjust its speed and directional uncertainty (i.e., magnitude and frequency of random directional changes) during chase and escape trials. These factors had a significant impact on participants' performance in both chasing and escaping trials. We developed a simple geometrical model of potential chaser/escaper interactions to distinguish pursuit from interception chasing trajectories. We found that participants initially pursued the target but switched to a late interception strategy. The amount of late interception strategy followed an inverted U-shaped curve with the highest values at intermediate speeds. We tested the applicability of our task and methods in children who showed a robust developmental improvement in task performance and late interception strategy. Our task constitutes a flexible system in a virtual space for studying chasing and escaping behavior in adults and children. Our analytical methods allow detecting subtle changes in interception strategies, a valuable tool for studying the maturation of predictive and prospective systems, with a high potential to contribute to cognitive and developmental research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams.

The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for "printing" memory engrams across brain regions, and the role of identified brain circuits in memory retrieval. With advanced genetic methods, we combinatorially blocked presynaptic output and manipulated N-methyl-D-aspartate receptor (NMDAR) in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) before and after cued fear conditioning. Further, we tagged fear-activated neurons during associative learning for optogenetic memory recall. We found that presynaptic mPFC and postsynaptic BLA NMDARs are required for fear memory formation, but not expression. Our results provide strong evidence that NMDAR-dependent synaptic plasticity drives multi-trace systems consolidation for the sequential printing of fear memory engrams from BLA to mPFC and, subsequently, to the other regions, for flexible memory retrieval.

Two-stage reinforcement learning task predicts psychological traits.

External sources of information influence human actions. However, psychological traits (PTs), considered internal variables, also play a crucial role in decision making. PTs are stable across time and contexts and define the set of behavioral repertoires that individuals express. Here, we explored how multiple metrics of adaptive behavior under uncertainty related to several PTs. Participants solved a reversal-learning task with volatile contingencies, from which we characterized a detailed behavioral profile based on their response sequences. We then tested the relationship between this multimetric behavioral profile and scores obtained from self-report psychological questionnaires. The PT measurements were based on the Hierarchical Taxonomy Of Psychopathology (HiTOP) model. By using multiple linear regression models (MLRMs), we found that the learning curves predicted important differences in the PTs and task response times. We confirmed the significance of these relationships by using random permutations of the predictors of the MLRM. Therefore, the behavioral profile configurations predicted the PTs and served as a "fingerprint" to identify participants with a high certainty level. We discuss briefly how this characterization and approach could contribute to better nosological classifications.

Response Time Distributions and the Accumulation of Visual Evidence in Freely Moving Mice.

Response time (RT) distributions are histograms of the observed RTs for discriminative choices, comprising a rich source of empirical information to study perceptual processes. The drift-diffusion model (DDM), a mathematical formulation predicting decision tasks, reproduces the RT distributions, contributing to our understanding of these processes from a theoretical perspective. Notably, although the mouse is a popular model system for studying brain function and behavior, little is known about mouse perceptual RT distributions, and their description from an information-accumulation perspective. We combined an automated visual discrimination task with pharmacological micro-infusions of targeted brain regions to acquire thousands of responses from freely-moving adult mice. Both choices and escape latencies showed a strong dependency on stimulus discriminability. By applying a DDM fit to our experimental data, we found that the rate of incoming evidence (drift rate) increased with stimulus contrast but was reversibly impaired when inactivating the primary visual cortex (V1). Other brain regions involved in the decision-making process, the posterior parietal cortex (PPC) and the frontal orienting fields (FOF), also influenced relevant parameters from the DDM. The large number of empirical observations that we collected for this study allowed us to achieve accurate convergence for the model fit. Therefore, changes in the experimental conditions were mirrored by changes in model parameters, suggesting the participation of relevant brain areas in the decision-making process. This approach could help interpret future studies involving attention, discrimination, and learning in adult mice.

Random noise stimulation in the treatment of patients with neurological disorders.

Random noise stimulation technique involves applying any form of energy (for instance, light, mechanical, electrical, sound) with unpredictable intensities through time to the brain or sensory receptors to enhance sensory, motor, or cognitive functions. Random noise stimulation initially employed mechanical noise in auditory and cutaneous stimuli, but electrical energies applied to the brain or the skin are becoming more frequent, with a series of clinical applications. Indeed, recent evidence shows that transcranial random noise stimulation can increase corticospinal excitability, improve cognitive/motor performance, and produce beneficial aftereffects at the behavioral and psychological levels. Here, we present a narrative review about the potential uses of random noise stimulation to treat neurological disorders, including attention deficit hyperactivity disorder, schizophrenia, amblyopia, myopia, tinnitus, multiple sclerosis, post-stroke, vestibular-postural disorders, and sensitivity loss. Many of the reviewed studies reveal that the optimal way to deliver random noise stimulation-based therapies is with the concomitant use of neurological and neuropsychological assessments to validate the beneficial aftereffects. In addition, we highlight the requirement of more randomized controlled trials and more physiological studies of random noise stimulation to discover another optimal way to perform the random noise stimulation interventions.

Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex.

G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. Researchers frequently study neuromodulation via these GPCR-subtypes on a 'cell-by-cell' basis. Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. Correlation strength increased with age but dropped when randomly removing genes from their corresponding groups. These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. Well-orchestrated interactions by neuromodulatory-GPCR ensembles could be crucial for the brain to function as a highly integrated complex system.

Clustering of neuropsychological traits of preschoolers.

Neuropsychological tests (targeting cognitive, linguistic, motor, and executive abilities) are grouped in neuropsychological domains that are thought to be stable through adulthood. However, this assumption does not always hold true, particularly during young children's early developmental phase. Here, we explored how the neuropsychological profile of typical Spanish-speaking preschoolers varied and consolidated with age. We recruited 643 monolingual Latin-American children from Mexico, Colombia, and Guatemala, with ages spanning from 30 to 71 months of age, and applied a novel neuropsychological examination which combined a total of 52 tests covering five classical neuropsychological domains: receptive, expressive, attention/memory, processing, and executive functions. These tests' scores uncovered a correlational structure across neuropsychological functions that could not be explained by chance. Notably, these correlations' overall strength, but not their interdependence across domains, dramatically increased with age. Moreover, by applying conventional clustering techniques to classify the experimental data, we found a stable representation of two clusters of children with distinctive traits, with cultural factors contributing to this classification scheme. We also found that the tasks were well organized in a network of abilities, where nodes with highest highest interconnectedness were those that required multimodal processing. These results contribute to our understanding of children's 'normal' development and could help identify how failure in particular functions forecasts the emergence of neurodevelopmental disorders. Our analytic methods might become useful to characterize individual differences and improve educational practices and interventions.

Isomorphic decisional biases across perceptual tasks.

Humans adjust their behavioral strategies to maximize rewards. However, in the laboratory, human decisional biases exist and persist in two alternative tasks, even when this behavior leads to a loss in utilities. Such biases constitute the tendency to choose one action over others and emerge from a combination of external and internal factors that are specific for each individual. Here, we explored the idea that internally-mediated decisional biases should stably occur and, hence, be reflected across multiple behavioral tasks. Our experimental results confirm this notion and illustrate how participants exhibited similar choice biases across days and tasks. Moreover, we show how side-choice behavior in a two alternative choice task served to identify participants, suggesting that individual traits could underlie these choice biases. The tasks and analytic tools developed for this study should become instrumental in exploring the interaction between internal and external factors that contribute to decisional biases. They could also serve to detect psychopathologies that involve aberrant levels of choice variability.

The Claustrum is Involved in Cognitive Processes Related to the Classical Conditioning of Eyelid Responses in Behaving Rabbits.

It is assumed that the claustrum (CL) is involved in sensorimotor integration and cognitive processes. We recorded the firing activity of identified CL neurons during classical eyeblink conditioning in rabbits, using a delay paradigm in which a tone was presented as conditioned stimulus (CS), followed by a corneal air puff as unconditioned stimulus (US). Neurons were identified by their activation from motor (MC), cingulate (CC), and medial prefrontal (mPFC) cortices. CL neurons were rarely activated by single stimuli of any modality. In contrast, their firing was significantly modulated during the first sessions of paired CS/US presentations, but not in well-trained animals. Neuron firing rates did not correlate with the kinematics of conditioned responses (CRs). CL local field potentials (LFPs) changed their spectral power across learning and presented well-differentiated CL-mPFC/CL-MC network dynamics, as shown by crossfrequency spectral measurements. CL electrical stimulation did not evoke eyelid responses, even in trained animals. Silencing of synaptic transmission of CL neurons by the vINSIST method delayed the acquisition of CRs but did not affect their presentation rate. The CL plays an important role in the acquisition of associative learning, mostly in relation to the novelty of CS/US association, but not in the expression of CRs.

Extracorporeal Cardiopulmonary Resuscitation in Acute Fulminant Myocarditis: A Case Report and Review of the Literature.

Fulminant myocarditis is a life-threatening fast progressive condition. We present a 7-year-old female patient admitted with a diagnosis of acute myocarditis with a rapidly progressive cardiac dysfunction despite conventional vasoactive and inotropic treatment. The patient presented with ventricular fibrillation and subsequent cardiac arrest. Cardiopulmonary resuscitation (CPR) was performed during 105 minutes before extracorporeal membrane oxygenation (ECMO) cannulation was performed. Effective hemodynamic function was obtained, and ECMO was weaned after 7 days, without neurological complications. There are not established extracorporeal cardiopulmonary resuscitation (eCPR) treatment criteria, and some international guidelines consider up to 100 minutes of "low flow" phase as a time limit to start the support. Some mortality risk factors for ECMO treatment mortality are female gender, renal failure, and arrhythmias. Pre-ECMO good prognostic factors are high levels of pH and blood lactate.

Distributed processing of side-choice biases.

Psychophysics describes how variations in stimulus strength lead to changes in perceptual performance. Yet, the contribution of non-sensory information processing to perceptual decision making is still not fully understood. For instance, in two-alternative forced-choice tasks, observers can exhibit tendencies to choose more one alternative over another, with no apparent goal or function. Such choice biases are highly prevalent in mice and, in free-choice tasks, they are insensitive to changes in stimulus discriminability. Thus, a reasonable proposal is that these side-choice biases could derive from functional asymmetries in sensory processing, decision making, or both. Here, we explored how different circuits participate in the production of choice biases in adult mice. We found that the magnitude of the changes in biased choice behavior depended on the inactivated region. Indeed, contralateral, but not ipsilateral, inactivations of the primary visual and posterior parietal cortices reduced the probability of mice choosing their preferred side. In contrast, ipsilateral inactivations of the subtantia nigra pars reticulata and of the frontal orienting fields, reduced and increased the probabilities of mice choosing their preferred side, respectively. These results demonstrate that internal circuit processing contributes to side-choice behavior and illustrates how distinct brain regions could participate in producing normal to aberrant levels of choice variability.

Adaptive Choice Biases in Mice and Humans.

The contribution of non-sensory information processing to perceptual decision making is not fully understood. Choice biases have been described for mice and humans and are highly prevalent even if they decrease rewarding outcomes. Choice biases are usually reduced by discriminability because stimulus strength directly enables the adjustments in the decision strategies used by decision-makers. However, choice biases could also derive from functional asymmetries in sensory processing, decision making, or both. Here, we tested how particular experimental contingencies influenced the production of choice biases in mice and humans. Our main goal was to establish the tasks and methods to jointly characterize psychometric performance and innate side-choice behavior in mice and humans. We implemented forced and un-forced visual tasks and found that both species displayed stable levels of side-choice biases, forming continuous distributions from low to high levels of choice stereotypy. Interestingly, stimulus discriminability reduced the side-choice biases in forced-choice, but not in free-choice tasks. Choice biases were stable in appearance and intensity across experimental days and could be employed to identify mice and human participants. Additionally, side- and alternating choices could be reinforced for both mice and humans, implying that choice biases were adaptable to non-visual manipulations. Our results highlight the fact that internal and external elements can influence the production of choice biases. Adaptations of our tasks could become a helpful diagnostic tool to detect aberrant levels of choice variability.

Non-stationary Salience Processing During Perceptual Training in Humans.

Performance in sensory tasks improves with practice. Some theories suggest that the generalization of learning depends on task difficulty. In consequence, most studies have focused on measuring learning specificity, and perceptual impact after training completes. However, how exactly sustained changes in task difficulty influence the learning curves and how this affects the efficiency of perceptual discrimination is not well understood. Here, we adapted a visual task for humans by creating monocular training programs with increasing (SIMinc) and decreasing (SIMdec) stimulus similarities. We found a marked improvement in all participants after 10 days of training, with an almost complete transfer of learning to the untrained eyes. Interestingly, the training paradigms led to drastically different learning curves for the SIMinc and SIMdec groups. The learning curves were best predicted by an associative learning model that allowed stimuli to gain or lose salience depending on how the subject's learned about them. On addition, a non-stationary sequential sampling model that jointly accounts for choice and RT distributions revealed that the SIMinc group led to faster evidence accumulation rate relative to the SIMdec group. Altogether, our results illustrate how different learning trajectories influenced attentional salience processing leading to distinctive stimulus processing efficiencies. This crucial interdependence determines how observers learn to guide their attention towards visual stimuli in search for a decision.

Fictive Scratching Patterns in Brain Cortex-Ablated, Midcollicular Decerebrate, and Spinal Cats.

Background: The spinal cord's central pattern generators (CPGs) have been explained by the symmetrical half-center hypothesis, the bursts generator, computational models, and more recently by connectome circuits. Asymmetrical models, at odds with the half-center paradigm, are composed of extensor and flexor CPG modules. Other models include not only flexor and extensor motoneurons but also motoneuron pools controlling biarticular muscles. It is unknown whether a preferred model can explain some particularities that fictive scratching (FS) in the cat presents. The first aim of this study was to investigate FS patterns considering the aiming and the rhythmic periods, and second, to examine the effects of serotonin (5HT) on and segmental inputs to FS. Methods: The experiments were carried out first in brain cortex-ablated cats (BCAC), then spinalized (SC), and for the midcollicular (MCC) preparation. Subjects were immobilized and the peripheral nerves were used to elicit the Monosynaptic reflex (MR), to modify the scratching patterns and for electroneurogram recordings. Results: In BCAC, FS was produced by pinna stimulation and, in some cases, by serotonin. The scratching aiming phase (AP) initiates with the activation of either flexor or extensor motoneurons. Serotonin application during the AP produced simultaneous extensor and flexor bursts. Furthermore, WAY 100635 (5HT1A antagonist) produced a brief burst in the tibialis anterior (TA) nerve, followed by a reduction in its electroneurogram (ENG), while the soleus ENG remained silent. In SC, rhythmic phase (RP) activity was recorded in the soleus motoneurons. Serotonin or WAY produced FS bouts. The electrical stimulation of Ia afferent fibers produced heteronymous MRes waxing and waning during the scratch cycle. In MCC, FS began with flexor activity. Electrical stimulation of either deep peroneus (DP) or superficial peroneus (SP) nerves increased the duration of the TA electroneurogram. Medial gastrocnemius (MG) stretching or MG nerve electrical stimulation produced a reduction in the TA electroneurogram and an initial MG extensor burst. MRes waxed and waned during the scratch cycle. Conclusion: Descending pathways and segmental afferent fibers, as well as 5-HT and WAY, can change the FS pattern. To our understanding, the half-center hypothesis is the most suitable for explaining the AP in MCC.

Adrenergic Modulation of Visually-Guided Behavior.

Iontophoretic application of norepinephrine (NE) into the primary visual cortex (V1) in vivo reduces spontaneous and evoked activity, without changing the functional selectivity of cortical units. One possible consequence of this phenomenon is that adrenergic receptors (ARs) regulate the signal-to-noise ratio (SNR) of neural responses in this circuit. However, despite such strong inhibitory action of NE on neuronal firing patterns in V1, its specific action on visual behavior has not been studied. Furthermore, the majority of observations regarding cortical NE from in vivo recordings have been performed in anesthetized animals and have not been tested behaviorally. Here, we describe how micro-infusion of AR agonists/antagonists into mouse V1 influences visually-guided behavior at different contrasts and spatial frequencies. We found that cortical activation of α1- and ß-AR produced a substantial reduction in visual discrimination performance at high contrasts and low spatial frequencies, consistent with a divisive effect. This reduction was reversible and was accompanied by a rise in escape latencies as well as an increase in the group averaged choice variance as a function of stimulus contrast. We conclude that pharmacological activation of cortical AR regulates visual perception and adaptive behavior through a divisive gain control of visual responses.

An Automated Water Task to Test Visual Discrimination Performance, Adaptive Strategies and Stereotyped Choices in Freely Moving Mice.

We describe an automated training/testing system for adult mice that allows reliable quantification of visual discrimination capacities, adaptive swimming strategies, and stereotyped choices with minimal human intervention. The experimental apparatus consists of a hexagonal swimming pool with an internal decision zone leading to three interior arms with two software-controlled platforms inside of each arm. Each experimental trial consists in projecting a "positive" conditioned discriminative stimulus (SD) in one randomly chosen arm, whereas the other two arms project non-reinforced stimuli (the delta stimuli, SΔ). By employing a classical behavioral training schedule, the mice learn to swim toward the arm that displays the SD, because it predicts the presence of two elevated platforms located symmetrically to the left and right side of the projecting monitor. Separate behavioral components for discriminative and stereotyped choice behavior can be identified through this geometric arrangement. In addition, the projection in real-time of either static or dynamic visual stimuli allows the usage of training programs contingent on current behavioral performance. We validated the system by characterizing the visual acuity and contrast sensitivities in a group of trained mice. By employing pharmacological manipulations, we found that the mice required an intact functioning of the primary visual cortex (V1) to solve the hexagonal pool. Overall, the automated training system constitutes a reliable, rapid, and inexpensive method to quantify visual capacities of mice. It can be used to characterize visual and non-visual factors of choice behavior. It can also be combined with manipulations of visual experience and pharmacological micro-infusions to investigate integrated brain function and learning processes in adult mice over consecutive days.