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Neurobiology of Learning and Memory Jun 2024Psilocybin may provide a useful treatment for mood disorders including anxiety and depression but its mechanisms of action for these effects are not well understood....
Psilocybin may provide a useful treatment for mood disorders including anxiety and depression but its mechanisms of action for these effects are not well understood. While recent preclinical work has begun to assess psilocybin's role in affective behaviors through innate anxiety or fear conditioning, there is scant evidence for its role in conflict between reward and punishment. The current study was designed to determine the impact of psilocybin on the learning of reward-punishment conflict associations, as well as its effects after learning, in male and female rats. We utilized a chained schedule of reinforcement that involved execution of safe and risky reward-guided actions under uncertain punishment. Different patterns of behavioral suppression by psilocybin emerged during learning versus after learning of risky action-reward associations. Psilocybin increased behavioral suppression in female rats as punishment associations were learned. After learning, psilocybin decreased behavioral suppression in both sexes. Thus, psilocybin produces divergent effects on action suppression during approach-avoidance conflict depending on when the conflict is experienced. This observation may have implications for its therapeutic mechanism of action.
PubMed: 38909970
DOI: 10.1016/j.nlm.2024.107954 -
Biological Psychiatry. Cognitive... Jun 2024Binge Eating Disorder (BED) is thought of as a disorder of cognitive control but evidence regarding its neurocognitive mechanisms is inconclusive. Key limitations in...
BACKGROUND
Binge Eating Disorder (BED) is thought of as a disorder of cognitive control but evidence regarding its neurocognitive mechanisms is inconclusive. Key limitations in prior research are a lack of consistent separation between effects of BED and obesity, and a disregard for self-report evidence suggesting that neurocognitive alterations may emerge primarily in loss- or harm-avoidance contexts.
METHODS
Addressing these gaps, this longitudinal study investigated behavioral flexibility and its underlying neuro-computational processes in reward-seeking and loss-avoidance contexts. Obese participants with BED (BED), without BED (OB), and healthy normal-weight participants (NW) (N=96) performed a probabilistic reversal learning task during functional imaging, with different blocks focused on obtaining wins or avoiding losses. They were reinvited for a 6-months follow-up.
RESULTS
Analyses informed by computational models of reinforcement learning showed that unlike BED, OB performed worse in the win than the loss condition. Computationally, this was explained by differential learning sensitivities in the win vs loss conditions between groups. In the brain, this was echoed in differential neural learning signals in the ventromedial prefrontal cortex (vmPFC) per condition. The differences were subtle, but scaled with BED symptoms, such that more severe BED symptoms were associated with increasing bias towards improved learning from wins vs losses. Across conditions, OB switched more between choice options than NW. This was reflected in diminished representation of choice certainty in the vmPFC.
CONCLUSIONS
Our study highlights the importance of distinguishing between obesity with and without BED to identify unique neuro-computational alterations underlying different styles of maladaptive eating behavior.
PubMed: 38909896
DOI: 10.1016/j.bpsc.2024.06.002 -
Journal of Ethnopharmacology Jun 2024Sugarcane (Saccharum officinarum L.) is reported by traditional medicine as tonic, stimulating and beneficial in increasing resistance to fatigue. Previous preclinical...
ETHNOPHARMACOLOGICAL RELEVANCE
Sugarcane (Saccharum officinarum L.) is reported by traditional medicine as tonic, stimulating and beneficial in increasing resistance to fatigue. Previous preclinical studies in rats using aqueous extract of sugarcane leaves (AE) revealed pharmacological effects on the central nervous and cardiovascular systems involving the participation of dopaminergic pathways. This neurotransmission system is also related to motor, emotional and cognitive activities, which could, in part, justify the ethnopharmacological information.
AIM OF STUDY
The present study aimed to investigate the motor, emotional and cognitive activities of rats submitted to AE treatment using behavioral tests in order to correlate the pharmacological effects with the therapeutic benefits postulated by traditional medicine. Additionally, the chemical profile of AE was evaluated by HPLC-UV/Vis, and the presence of shikimic acid, vitexin, and ferulic acid, as possible chemical markers, was investigated through comparisons of chemical parameters with the authentic patterns, and a UV-Vis scan of known spectra.
MATERIAL AND METHODS
Rats received water (1.5 mL/kg, p.o.) and AE (0.5, 10 and 500 mg/kg, p.o.) in the absence and presence of haloperidol (0.5 mg/kg, i.p.), 90 min before open field; rotarod; elevated plus maze and inhibitory avoidance tests for investigation of motor; emotional and cognitive responses. As a positive control was used apomorphine (0.25 mg/kg, s.c.). The chemical profile of AE was evaluated by HPLC-UV/Vis and the presence of shikimic acid, vitexin and ferulic acid, as possible chemical markers, was investigated through comparisons with the retention times, an increase of the integral of the peak area determined by co-injection of AE with the authentic patterns, and a UV-Vis scan of known spectra.
RESULTS
In open field, it revealed that AE increased locomotion; reduced rearing but did not change freezing and grooming. Besides, AE increased motor performance in rotarod and reduced anxiety in elevated plus maze. A relation dose-response was observed in these tests where the lowest dose of AE was more effective in developing pharmacological responses. Previous administration of haloperidol inhibited the responses of AE. Inhibitory avoidance test revealed that AE did not modify fast-learning and associative memory.
CONCLUSIONS
Sugarcane induced psychostimulant, anxiolytic-like effects, and improvement of motor performance in rats, with the involvement of dopaminergic pathways. The present study points to AE as a potential adaptogen but, in addition to behavioral assessments, metabolic and molecular aspects, that involve the participation of a variety of regulatory systems, will be investigated in futures studies. Phytochemical analyses showed that AE is a complex matrix and revealed shikimic acid, vitexin, and ferulic acid as potential chemical markers.
PubMed: 38908491
DOI: 10.1016/j.jep.2024.118476 -
Physical Review. E May 2024Using a statistical-mechanics approach, we study the effects of geometry and self-avoidance on the ordering of slender filaments inside nonisotropic containers,...
Using a statistical-mechanics approach, we study the effects of geometry and self-avoidance on the ordering of slender filaments inside nonisotropic containers, considering cortical microtubules in plant cells, and packing of genetic material inside viral capsids as concrete examples. Within a mean-field approximation, we show analytically how the shape of the container, together with self-avoidance, affects the ordering of the stiff rods. We find that the strength of the self-avoiding interaction plays a significant role in the preferred packing orientation, leading to a first-order transition for oblate cells, where the preferred orientation changes from azimuthal, along the equator, to a polar one, when self-avoidance is strong enough. While for prolate spheroids the ground state is always a polar-like order, strong self-avoidance results with a deep metastable state along the equator. We compute the critical surface describing the transition between azimuthal and polar ordering in the three-dimensional parameter space (persistence length, eccentricity, and self-avoidance) and show that the critical behavior of this system is in fact related to the butterfly catastrophe model. We calculate the pressure and shear stress applied by the filament on the surface, and the injection force needed to be applied on the filament in order to insert it into the volume. We compare these results to the pure mechanical study where self-avoidance is ignored, and discuss similarities and differences.
PubMed: 38907449
DOI: 10.1103/PhysRevE.109.054111 -
IEEE Transactions on Pattern Analysis... Jun 2024A desirable objective in self-supervised learning (SSL) is to avoid feature collapse. Whitening loss guarantees collapse avoidance by minimizing the distance between...
A desirable objective in self-supervised learning (SSL) is to avoid feature collapse. Whitening loss guarantees collapse avoidance by minimizing the distance between embeddings of positive pairs under the conditioning that the embeddings from different views are whitened. In this paper, we propose a framework with an informative indicator to analyze whitening loss, which provides a clue to demystify several interesting phenomena and a pivoting point connecting to other SSL methods. We show that batch whitening (BW) based methods do not impose whitening constraints on the embedding but only require the embedding to be full-rank. This full-rank constraint is also sufficient to avoid dimensional collapse. We further demonstrate that the stable rank of the embedding is invariant during training by gradient descent, given the assumption that embedding is updated with an infinitely small learning rate. Based on our analysis, we propose channel whitening with random group partition (CW-RGP), which exploits the advantages of BW-based methods in preventing collapse and avoids their disadvantages requiring large batch size. Experimental results on ImageNet classification and COCO object detection reveal that the proposed CW-RGP possesses a promising potential for learning good representations.
PubMed: 38905085
DOI: 10.1109/TPAMI.2024.3417438 -
JBJS Essential Surgical Techniques 2024A number of techniques have been described to enter the capsule and gain access to the hip joint during hip arthroscopy. Among these, the interportal and T-capsulotomies...
BACKGROUND
A number of techniques have been described to enter the capsule and gain access to the hip joint during hip arthroscopy. Among these, the interportal and T-capsulotomies are the most commonly utilized; however, these approaches transect the iliofemoral ligament, which normally resists anterior subluxation and stabilizes extension. Thus, these approaches may introduce capsuloligamentous instability and have been associated with complications such as dislocation, postoperative pain, microinstability, seroma, and heterotopic ossification. Although prior literature has demonstrated durable mid-term results for patients undergoing capsulotomies with capsular closure, avoidance of iatrogenic injury to the hip capsule altogether is preferable. Thus, the puncture capsulotomy technique we present is minimally invasive, preserves the biomechanics of the hip joint and capsule without disrupting the iliofemoral ligament, and allows for appropriate visualization of the joint through placement of multiple small portals.
DESCRIPTION
Following induction of anesthesia and with the patient supine on a hip traction table, the nonoperative leg is positioned at 45° abduction with support of a well-padded perineal post, and the operative hip is placed into valgus against the post. Intra-articular fluid distention with normal saline solution is utilized to achieve approximately 9 mm of inferior migration of the femoral head and decrease risk of iatrogenic nerve injury. Then, under fluoroscopic guidance, an anterolateral portal is created 1 cm anterior and 1 cm superior to the greater trochanter at an approximately 15° to 20° angle. Second, via arthroscopic visualization, the anterior portal is created 1 cm distal and 1 cm lateral to the intersection of a vertical line drawn at the anterior superior iliac spine and a horizontal line at the level of the anterolateral portal. Third, equidistant between the anterior and anterolateral portals, the mid-anterior portal is created distally. Finally, at one-third of the distance between the anterior superior iliac spine and the anterolateral portal, the Dienst portal is created. Thus, these 4 portals form a quadrilateral arrangement through which puncture capsulotomy can be performed.
ALTERNATIVES
Alternative approaches to the hip capsule include interportal and T-capsulotomies, with or without capsular closure. Although the most frequently utilized, these approaches transect the iliofemoral ligament and thus may introduce capsuloligamentous instability.
RATIONALE
The puncture capsulotomy technique has the advantage of maintaining the integrity of the capsule through the placement of 4 small portals. The technique does not transect the iliofemoral ligament and thus does not introduce capsuloligamentous instability. Furthermore, although good mid-term outcomes have been reported with capsular closure, the present technique avoids creating unnecessary injury to the capsule and complications of an unrepaired capsule or, conversely, of plication.
EXPECTED OUTCOMES
Patients who underwent the puncture capsulotomy technique showed significant improvements in multiple functional outcome scores at a mean follow-up of 30.4 months, including the International Hip Outcome Tool (iHOT-33) (39.6 preoperatively to 76.1 postoperatively), Hip Outcome Score-Activities of Daily Living subscale (HOS-ADL) (70.0 to 89.3), HOS Sport-Specific Subscale (HOS-SSS) (41.8 to 75.7), and modified Harris hip score (mHHS) (60.1 to 84.9). At 2 years postoperatively with respect to iHOT-33, 81.0% of patients achieved the minimal clinically important difference, 62.0% achieved the patient acceptable symptom state, and 58.9% achieved substantial clinical benefit. In addition, mean visual analog scale pain scores improved significantly over the follow-up period (6.3 to 2.2; p < 0.001). Finally, there were zero occurrences of infection, osteonecrosis of the femoral head, dislocation or instability, or femoral neck fracture in patients treated with puncture capsulotomy.
IMPORTANT TIPS
Anterolateral portal placement should be performed using the intra-articular fluid distention technique with fluoroscopy to avoid risk of iatrogenic labral damage and distraction-induced neurapraxia. Subsequent portals must then be placed under direct arthroscopic visualization.On establishment of the anterolateral portal, the scope should be switched to the anterior portal to ensure that the anterolateral portal has not been placed through the labrum and to adjust its placement to better access pathology. This portal, as well as all others, may be subsequently modified by adjusting the angle of the cannula, without making a new skin incision.If a cam lesion is located more anteromedially or posterolaterally, an additional accessory portal may be made distal or proximal to the anterolateral portal, respectively, in order to enhance visualization.Intermittent traction is utilized throughout the surgery. No traction is utilized during preparing and draping, suture tensioning and tie-down, and femoroplasty, with minimal traction during acetabuloplasty; these precautions serve to prevent iatrogenic superficial peroneal nerve injury.There can be a steep learning curve for this technique. In particular, greater surgical experience is required to perform adequate femoral osteoplasty for large cam lesions with this approach.Instrument maneuverability and visualization can be somewhat constrained with this approach.It is more difficult to perform certain procedures with this technique, including segmental and circumferential labral reconstructions, particularly with remote grafts.
ACRONYMS AND ABBREVIATIONS
iHOT-33 = International Hip Outcome Tool-33HOS-ADL = Hip Outcome Score-Activities of Daily Living subscaleHOS-SSS = Hip Outcome Score-Sport-Specific SubscaleAP = anteroposteriorMRA = magnetic resonance arthrogramMRI = magnetic resonance imagingCT = computed tomographyASIS = anterior superior iliac spinemHHS = modified Harris hip score.
PubMed: 38903605
DOI: 10.2106/JBJS.ST.23.00061 -
Frontiers in Neuroscience 2024Reward-seeking behavior is frequently associated with risk of punishment. There are two types of punishment: positive punishment, which is defined as addition of an...
Reward-seeking behavior is frequently associated with risk of punishment. There are two types of punishment: positive punishment, which is defined as addition of an aversive stimulus, and negative punishment, involves the omission of a rewarding outcome. Although the medial prefrontal cortex (mPFC) is important in avoiding punishment, whether it is important for avoiding both positive and negative punishment and how it contributes to such avoidance are not clear. In this study, we trained male mice to perform decision-making tasks under the risks of positive (air-puff stimulus) and negative (reward omission) punishment, and modeled their behavior with reinforcement learning. Following the training, we pharmacologically inhibited the mPFC. We found that pharmacological inactivation of mPFC enhanced the reward-seeking choice under the risk of positive, but not negative, punishment. In reinforcement learning models, this behavioral change was well-explained as an increase in sensitivity to reward, rather than a decrease in the strength of aversion to punishment. Our results suggest that mPFC suppresses reward-seeking behavior by reducing sensitivity to reward under the risk of positive punishment.
PubMed: 38903603
DOI: 10.3389/fnins.2024.1412509 -
Progress in Neuro-psychopharmacology &... Jun 2024The ventral pallidum (VP) receives its primary inputs from the nucleus accumbens (NAC) and the basolateral amygdala (BLA). We demonstrated recently that in the VP, the...
The ventral pallidum (VP) receives its primary inputs from the nucleus accumbens (NAC) and the basolateral amygdala (BLA). We demonstrated recently that in the VP, the D2 DA receptor (DR) agonist quinpirole dose-dependently facilitates memory consolidation in inhibitory avoidance and spatial learning. In the VP, DR can be found both on NAC and BLA terminals. According to our hypothesis, quinpirole microinjected into the VP can facilitate memory consolidation via modulation of synaptic plasticity on NAC and/or BLA terminals. The effect of intra-VP quinpirole on BLA-VP and NAC shell-VP synapses was investigated via a high frequency stimulation (HFS) protocol. Quinpirole was administered in three doses into the VP of male Sprague-Dawley rats after HFS; controls received vehicle. To examine whether an interaction between the NAC shell and the BLA at the level of the VP was involved, tetrodotoxin (TTX) was microinjected into one of the nuclei while stimulating the other nucleus. Our results showed that quinpirole dose-dependently modulates BLA-VP and NAC shell-VP synapses, similar to those observed in inhibitory avoidance and spatial learning, respectively. The lower dose inhibits BLA inputs, while the larger doses facilitates NAC shell inputs. The experiments with TTX demonstrates that the two nuclei do not influence each others' evoked responses in the VP. Power spectral density analysis demonstrated that independent from the synaptic facilitation, intra-VP quinpirole increases the amplitude of gamma frequency band after NAC HFS, and BLA tonically suppresses the NAC's HFS-induced gamma facilitation. In contrast, HFS of the BLA results in a delayed, transient increase in the amplitude of the gamma frequency band correlating with the LTP of the P1 component of the VP response to BLA stimulation. Furthermore, our results demonstrate that the BLA plays a prominent role in the generation of the delta oscillations: HFS of the BLA leads to a gradually increasing delta frequency band facilitation over time, while BLA inhibition blocks the NAC's HFS induced strong delta facilitation. These findings demonstrate that there is a complex interaction between the NAC shell region and the VP, as well as the BLA and the VP, and support the important role of VP DRs in the regulation of limbic information flow.
PubMed: 38901759
DOI: 10.1016/j.pnpbp.2024.111059 -
Preventive Medicine Jun 2024To investigate the relationship between Body Mass Index (BMI) and adherence to recommended screening tests, addressing gaps in previous literature by utilizing a large...
OBJECTIVE
To investigate the relationship between Body Mass Index (BMI) and adherence to recommended screening tests, addressing gaps in previous literature by utilizing a large cohort, while considering longitudinal changes in weight and the type of screening.
METHODS
Data from Clalit Health Services in Israel were retrospectively analyzed, including participants aged 50 and above from 2002 to 2021. BMI measurements and various screening test records were examined. Generalized Estimating Equations were employed for analysis, adjusting for potential confounding variables, including age, gender, geographic location, and socioeconomic status.
RESULTS
The study included 634,879 participants with 4,630,030 BMI measurements and 56,453,659 test records. Participants were categorized into BMI cohorts at the time of the test, with overweight and obese individuals showing lower odds of undergoing intimate examination-based screening tests (mammography, PAPS, and skin examination), as opposed to higher odds of several non-intimate tests (e.g., diabetes and eye disorder screenings).
DISCUSSION
Our findings suggest that individuals with overweight and obesity are less likely to undergo screenings involving intimate physical examinations, potentially due to weight stigma and discomfort. This avoidance behavior may contribute to increased morbidity rates in these populations. Interventions addressing weight stigma, improving access to care, and enhancing patient engagement are warranted.
PubMed: 38901741
DOI: 10.1016/j.ypmed.2024.108045 -
Frontiers in Robotics and AI 2024Soft robots exhibit complex nonlinear dynamics with large degrees of freedom, making their modelling and control challenging. Typically, reduced-order models in time or...
Soft robots exhibit complex nonlinear dynamics with large degrees of freedom, making their modelling and control challenging. Typically, reduced-order models in time or space are used in addressing these challenges, but the resulting simplification limits soft robot control accuracy and restricts their range of motion. In this work, we introduce an end-to-end learning-based approach for fully dynamic modelling of any general robotic system that does not rely on predefined structures, learning dynamic models of the robot directly in the visual space. The generated models possess identical dimensionality to the observation space, resulting in models whose complexity is determined by the sensory system without explicitly decomposing the problem. To validate the effectiveness of our proposed method, we apply it to a fully soft robotic manipulator, and we demonstrate its applicability in controller development through an open-loop optimization-based controller. We achieve a wide range of dynamic control tasks including shape control, trajectory tracking and obstacle avoidance using a model derived from just 90 min of real-world data. Our work thus far provides the most comprehensive strategy for controlling a general soft robotic system, without constraints on the shape, properties, or dimensionality of the system.
PubMed: 38899065
DOI: 10.3389/frobt.2024.1403733