Closed-loop microstimulations of the orbitofrontal cortex during real-life gaze interaction enhance dynamic social attention.

Neurons from multiple prefrontal areas encode several key variables of social gaze interaction. To explore the causal roles of the primate prefrontal cortex in real-life gaze interaction, we applied weak closed-loop microstimulations that were precisely triggered by specific social gaze events. Microstimulations of the orbitofrontal cortex, but not the dorsomedial prefrontal cortex or the anterior cingulate cortex, enhanced momentary dynamic social attention in the spatial dimension by decreasing the distance of fixations relative to a partner's eyes and in the temporal dimension by reducing the inter-looking interval and the latency to reciprocate the other's directed gaze. By contrast, on a longer timescale, microstimulations of the dorsomedial prefrontal cortex modulated inter-individual gaze dynamics relative to one's own gaze positions. These findings demonstrate that multiple regions in the primate prefrontal cortex may serve as functionally accessible nodes in controlling different aspects of dynamic social attention and suggest their potential for a therapeutic brain interface.

Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia.

Beliefs-attitudes toward some state of the environment-guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14). Computational analyses indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models, these results have implications for understanding paranoia.

An unbiased method to partition diverse neuronal responses into functional ensembles reveals interpretable population dynamics during innate social behavior.

In neuroscience, understanding how single-neuron firing contributes to distributed neural ensembles is crucial. Traditional methods of analysis have been limited to descriptions of whole population activity, or, when analyzing individual neurons, criteria for response categorization varied significantly across experiments. Current methods lack scalability for large datasets, fail to capture temporal changes and rely on parametric assumptions. There's a need for a robust, scalable, and non-parametric functional clustering approach to capture interpretable dynamics. To address this challenge, we developed a model-based, statistical framework for unsupervised clustering of multiple time series datasets that exhibit nonlinear dynamics into an a-priori-unknown number of parameterized ensembles called Functional Encoding Units (FEUs). FEU outperforms existing techniques in accuracy and benchmark scores. Here, we apply this FEU formalism to single-unit recordings collected during social behaviors in rodents and primates and demonstrate its hypothesis-generating and testing capacities. This novel pipeline serves as an analytic bridge, translating neural ensemble codes across model systems.

Development of a Marmoset Apparatus for Automated Pulling (MarmoAAP) to Study Cooperative Behaviors.

In recent years, the field of neuroscience has increasingly recognized the importance of studying animal behaviors in naturalistic environments to gain deeper insights into ethologically relevant behavioral processes and neural mechanisms. The common marmoset (Callithrix jacchus), due to its small size, prosocial nature, and genetic proximity to humans, has emerged as a pivotal model toward this effort. However, traditional research methodologies often fail to fully capture the nuances of marmoset social interactions and cooperative behaviors. To address this critical gap, we developed the Marmoset Apparatus for Automated Pulling (MarmoAAP), a novel behavioral apparatus designed for studying cooperative behaviors in common marmosets. MarmoAAP addresses the limitations of traditional behavioral research methods by enabling high-throughput, detailed behavior outputs that can be integrated with video and audio recordings, allowing for more nuanced and comprehensive analyses even in a naturalistic setting. We also highlight the flexibility of MarmoAAP in task parameter manipulation which accommodates a wide range of behaviors and individual animal capabilities. Furthermore, MarmoAAP provides a platform to perform investigations of neural activity underlying naturalistic social behaviors. MarmoAAP is a versatile and robust tool for advancing our understanding of primate behavior and related cognitive processes. This new apparatus bridges the gap between ethologically relevant animal behavior studies and neural investigations, paving the way for future research in cognitive and social neuroscience using marmosets as a model organism.

Automated 3D analysis of social head-gaze behaviors in freely moving marmosets.

Social communication relies on the ability to perceive and interpret the direction of others' attention, which is commonly conveyed through head orientation and gaze direction in both humans and non-human primates. However, traditional social gaze experiments in non-human primates require restraining head movements, which significantly limit their natural behavioral repertoire. Here, we developed a novel framework for accurately tracking facial features and three-dimensional head gaze orientations of multiple freely moving common marmosets (Callithrix jacchus). To accurately track the facial features of marmoset dyads in an arena, we adapted computer vision tools using deep learning networks combined with triangulation algorithms applied to the detected facial features to generate dynamic geometric facial frames in 3D space, overcoming common occlusion challenges. Furthermore, we constructed a virtual cone, oriented perpendicular to the facial frame, to model the head gaze directions. Using this framework, we were able to detect different types of interactive social gaze events, including partner-directed gaze and jointly-directed gaze to a shared spatial location. We observed clear effects of sex and familiarity on both interpersonal distance and gaze dynamics in marmoset dyads. Unfamiliar pairs exhibited more stereotyped patterns of arena occupancy, more sustained levels of social gaze across inter-animal distance, and increased gaze monitoring. On the other hand, familiar pairs exhibited higher levels of joint gazes. Moreover, males displayed significantly elevated levels of gazes toward females' faces and the surrounding regions irrespective of familiarity. Our study lays the groundwork for a rigorous quantification of primate behaviors in naturalistic settings.

Radiographic and Clinical Outcomes After Stand-Alone Anterior Lumbar Interbody Fusion for Symptomatic L5-S1 Retrolisthesis.

BACKGROUND AND OBJECTIVES: Degenerative lumbar spondylolisthesis is associated with significant pain and disability. The literature on the treatment options and clinical outcomes for lumbar anterolisthesis is robust, but very few reports specifically evaluate lumbar retrolisthesis. This study investigated surgical outcomes for symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 anterior lumbar interbody fusion (ALIF). METHODS: All patients with symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 ALIF at a single institution over a 7-year period were identified. Exhaustive nonoperative management had failed for all patients. Patients with previous lumbar fusion were excluded. Preoperative and postoperative radiographic images and patient-reported outcome measures for 20 patients (14 males and 6 females; mean [SD] age, 50.3 [13.7] years) were analyzed. RESULTS: The mean (SD) follow-up was 43.0 (23.7) months (range, 12.1-102.5 months). Patients experienced postoperative improvements in L5-S1 retrolisthesis (P = .048), L5-S1 disk height and angle (P < .001), L5 foraminal height (P < .001), L5-S1 lordosis (P < .001), and lumbar lordosis (P = .01). There were no significant changes in spinopelvic parameters. At the most recent follow-up, minimal clinically important differences in Oswestry Disability Index score, 36-Item Short-Form Survey (SF-36), and numerical rating scale score for leg pain were achieved in 11 of 20 (55%), 7 of 14 (50%), and 7 of 13 (54%) patients, respectively. All patients demonstrated fusion with no graft subsidence at up to 32 months. No patient experienced intraoperative complications, was readmitted, or required a subsequent posterior decompression or fusion because of refractory symptoms. CONCLUSION: In our cohort, stand-alone L5-S1 ALIF was associated with radiographic and clinical improvement in patients with symptomatic L5-S1 retrolisthesis.

Pseudarthrosis after four-level anterior cervical discectomy and fusion without posterior fixation.

OBJECTIVE: Fusion rates and long-term outcomes are well established for anterior cervical discectomy and fusion (ACDF) of 3 levels or fewer, but there is a paucity of similar data on 4-level fusions. The authors evaluated long-term fusion rates and clinical outcomes after 4-level ACDF without supplemental posterior instrumentation. METHODS: The authors retrospectively reviewed patients who underwent 4-level ACDF at a single institution with at least 1-year of radiological follow-up. Fusion was determined by measuring change in interspinous distance at each segment on dynamic radiographs or by the presence of bridging bone on CT scans at minimum 1-year follow-up. Clinical outcomes were assessed using Neck Disability Index and Short Form-36. RESULTS: A total of 63 patients (252 levels) met the inclusion criteria for the study, with a mean follow-up of 2.6 years. Complete radiographic fusion at all 4 levels was observed in 26 patients (41.3%). Of the 37 patients (58.7%) with radiographic pseudarthrosis, there was a mean of 1.35 nonfused levels. The fusion rate per level, however, was 80.2% (202/252 levels). The most common level demonstrating nonunion was the distal segment (C6-7), showing pseudarthrosis in 29 patients (46.8%), followed by the most proximal segment (C3-4) demonstrating nonunion in 9 patients (14.5%). The mean improvement in Neck Disability Index and Short Form-36 was 15.7 (p < 0.01) and 5.8 (p = 0.14), respectively, with improvement in both scores surpassing the minimum clinically important difference. One patient (1.6%) required revision surgery for symptomatic pseudarthrosis, and 5 patients (7.9%) underwent revision for symptomatic adjacent-segment disease. Patient-reported outcomes results are limited by the low rate of 1-year follow-up (50.8%), whereas reoperation data were available for all 63 patients. CONCLUSIONS: More than half of patients undergoing 4-level ACDF without posterior fixation demonstrated pseudarthrosis of at least 1 level-most commonly the distal C6-7 level. One patient required revision for symptomatic pseudarthrosis. Patient-reported outcomes showed significant improvements at 1-year follow-up, but clinical follow-up was limited. This is the largest series to date to evaluate fusion outcomes in 4-level ACDF.

The orbitofrontal cortex: A goal-directed cognitive map framework for social and non-social behaviors.

The orbitofrontal cortex (OFC) is regarded as one of the core brain areas in a variety of value-based behaviors. Over the past two decades, tremendous knowledge about the OFC function was gained from studying the behaviors of single subjects. As a result, our previous understanding of the OFC's function of encoding decision variables, such as the value and identity of choices, has evolved to the idea that the OFC encodes a more complex representation of the task space as a cognitive map. Accumulating evidence also indicates that the OFC importantly contributes to behaviors in social contexts, especially those involved in cooperative interactions. However, it remains elusive how exactly OFC neurons contribute to social functions and how non-social and social behaviors are related to one another in the computations performed by OFC neurons. In this review, we aim to provide an integrated view of the OFC function across both social and non-social behavioral contexts. We propose that seemingly complex functions of the OFC may be explained by its role in providing a goal-directed cognitive map to guide a wide array of adaptive reward-based behaviors in both social and non-social domains.

Dissociation of vicarious and experienced rewards by coupling frequency within the same neural pathway.

Vicarious reward, essential to social learning and decision making, is theorized to engage select brain regions similarly to experienced reward to generate a shared experience. However, it is just as important for neural systems to also differentiate vicarious from experienced rewards for social interaction. Here, we investigated the neuronal interaction between the primate anterior cingulate cortex gyrus (ACCg) and the basolateral amygdala (BLA) when social choices made by monkeys led to either vicarious or experienced reward. Coherence between ACCg spikes and BLA local field potential (LFP) selectively increased in gamma frequencies for vicarious reward, whereas it selectively increased in alpha/beta frequencies for experienced reward. These respectively enhanced couplings for vicarious and experienced rewards were uniquely observed following voluntary choices. Moreover, reward outcomes had consistently strong directional influences from ACCg to BLA. Our findings support a mechanism of vicarious reward where social agency is tagged by interareal coordination frequency within the same shared pathway.

Beyond cortex: The evolution of the human brain.

Human evolution has been marked by a striking increase in total brain volume relative to body size. While a prominent and characteristic feature of this volumetric shift has been the disproportionate expansion of association cortex across our evolutionary lineage, descent with modification is apparent throughout all neural systems in both human and nonhuman primates. However, despite evidence for the ubiquitous and complex influence of evolutionary forces on brain biology, within the psychological sciences the vast majority of the literature on human brain evolution is entirely corticocentric. This selective focus has contributed to a flawed theoretical framework in which the evolution of association cortex is viewed as an isolated process, removed from the rest of the brain. Here, we review our current understanding of how evolutionary pressures have acted across anatomically and functionally coupled networks, highlighting the diverse set of rules and principles that govern human brain development. In doing so we challenge the systemic mischaracterization of human cognition and behavior as a competition that pits phylogenetically recent cortical territories against evolutionarily ancient subcortical and cerebellar systems. Rather, we propose a comprehensive view of human brain evolution with critical importance for the use of animal models, theory development, and network-focused approaches in the study of behavior across health and disease. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Impact of exercise on physical health status in bladder cancer patients.

INTRODUCTION: There is a scarcity of data on the impact of behavioral habits, such as exercise, on physical health in patients with bladder cancer. We investigated the association of exercise on self-reported physical health status and examined the prevalence of bladder cancer patients with sedentary lifestyle. METHODS: We examined cross-sectional data of participants diagnosed with bladder cancer within the Behavioral Risk Factor Surveillance System (BRFSS) from 2016-2020. Patient health status was surveyed using self-reported measures, such as the total days per month when their "physical health is not good." The primary outcome was patient-reported poor physical health for more than 14 days within a one-month period. RESULTS: Out of 2 193 981 survey participants, we identified 936 with a history of bladder cancer. Nearly one in three bladder cancer patients reported being sedentary within the last month, as a total of 307 (32.8%) patients reported no exercise within the last 30 days. The remaining 628 (67.2%) reported exercising for at least one day within the last month. In multivariable logistic regression model analysis, we found that exercise is protective for self-reported poor physical health status (odds ratio 0.37, 95% confidence interval 0.25-0.56, p<0.001). Patients that exercised were less likely to report bad physical health. CONCLUSIONS: Approximately one in three bladder cancer patients report no exercise within 30 days, suggesting a sedentary lifestyle. Patients that are active are less likely to self-report poor physical health status. Implementation of exercise programs for bladder cancer patients could be promising in improving health status.

Closed-loop microstimulations of the orbitofrontal cortex during real-life gaze interaction enhance dynamic social attention.

The prefrontal cortex is extensively involved in social exchange. During dyadic gaze interaction, multiple prefrontal areas exhibit neuronal encoding of social gaze events and context-specific mutual eye contact, supported by a widespread neural mechanism of social gaze monitoring. To explore causal manipulation of real-life gaze interaction, we applied weak closed-loop microstimulations that were precisely triggered by specific social gaze events to three prefrontal areas in monkeys. Microstimulations of orbitofrontal cortex (OFC), but not dorsomedial prefrontal or anterior cingulate cortex, enhanced momentary dynamic social attention in the spatial dimension by decreasing distance of one's gaze fixations relative to partner monkey's eyes. In the temporal dimension, microstimulations of OFC reduced the inter-looking interval for attending to another agent and the latency to reciprocate other's directed gaze. These findings demonstrate that primate OFC serves as a functionally accessible node in controlling dynamic social attention and suggest its potential for a therapeutic brain interface.

Single-Position Anterior and Lateral Lumbar Fusion in the Supine Position: A Novel Technique for Multilevel Arthrodesis.

OBJECTIVE: Anterior lumbar interbody fusion (ALIF) and lateral lumbar interbody fusion are common techniques that typically require staged procedures when performed in combination. Interest is emerging in single-position surgery to increase operative efficiency. We report a novel surgical technique, supine extended reach lateral fusion, to perform ALIF and lateral lumbar interbody fusion with the patient in a single supine position. METHODS: A man in his fifties presented with degenerative levoscoliosis, spondylolisthesis, sagittal plane deformity, and progressive low back pain. He was offered L3-S1 anterolateral fusion. RESULTS: With the patient supine, a left abdominal paramedian incision was performed to gain anterior retroperitoneal access, and standard L5-S1 and L4-5 ALIFs were performed. The anterior incision was used for direct visualization, retraction, and bimanual dissection. A left lateral incision was then made to perform an L3-4 lateral lumbar interbody fusion. He subsequently underwent a second-stage L3-S1 posterior percutaneous fixation. The patient tolerated the procedures well, without complications. His postoperative radiograph findings confirmed acceptable implant positioning. He was discharged home in stable condition and was doing well at follow-up. CONCLUSIONS: This case description is the first report of the supine extended reach technique, which allows incorporation of anterior and lateral fusion constructs at adjacent levels without changing patient positioning. Many surgeons believe the ALIF to be the most powerful technique for achieving lordosis, and this technique enables concomitant lateral access in a supine position. It can also be used as an alternative strategy when anterior access to the disc space is unobtainable. Further clinical investigation of this technique is warranted.

Amygdala connectivity and implications for social cognition and disorders.

The amygdala is a hub of subcortical region that is crucial in a wide array of affective and motivation-related behaviors. While early research contributed significantly to our understanding of this region's extensive connections to other subcortical and cortical regions, recent methodological advances have enabled researchers to better understand the details of these circuits and their behavioral contributions. Much of this work has focused specifically on investigating the role of amygdala circuits in social cognition. In this chapter, we review both long-standing knowledge and novel research on the amygdala's structure, function, and involvement in social cognition. We focus specifically on the amygdala's circuits with the medial prefrontal cortex, the orbitofrontal cortex, and the hippocampus, as these regions share extensive anatomic and functional connections with the amygdala. Furthermore, we discuss how dysfunction in the amygdala may contribute to social deficits in clinical disorders including autism spectrum disorder, social anxiety disorder, and Williams syndrome. We conclude that social functions mediated by the amygdala are orchestrated through multiple intricate interactions between the amygdala and its interconnected brain regions, endorsing the importance of understanding the amygdala from network perspectives.

Interplay between the oxytocin and opioid systems in regulating social behaviour.

The influence of neuromodulators on brain activity and behaviour is undeniably profound, yet our knowledge of the underlying mechanisms, or ability to reliably reproduce effects across varying conditions, is still lacking. Oxytocin, a hormone that acts as a neuromodulator in the brain, is an example of this quandary; it powerfully shapes behaviours across nearly all mammalian species, yet when manipulated exogenously can produce unreliable or sometimes unexpected behavioural results across varying contexts. While current research is rapidly expanding our understanding of oxytocin, interactions between oxytocin and other neuromodulatory systems remain underappreciated in the current literature. This review highlights interactions between oxytocin and the opioid system that serve to influence social behaviour and proposes a parallel-mechanism hypothesis to explain the supralinear effects of combinatorial neuropharmacological approaches. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.

Prefrontal circuits guiding social preference: Implications in autism spectrum disorder.

Although Autism Spectrum Disorder (ASD) is increasing in diagnostic prevalence, treatment options are inadequate largely due to limited understanding of ASD's underlying neural mechanisms. Contributing to difficulties in treatment development is the vast heterogeneity of ASD, from physiological causes to clinical presentations. Recent studies suggest that distinct genetic and neurological alterations may converge onto similar underlying neural circuits. Therefore, an improved understanding of neural circuit-level dysfunction in ASD may be a more productive path to developing broader treatments that are effective across a greater spectrum of ASD. Given the social preference behavioral deficits commonly seen in ASD, dysfunction in circuits mediating social preference may contribute to the atypical development of social cognition. We discuss some of the animal models used to study ASD and examine the function and effects of dysregulation of the social preference circuits, notably the medial prefrontal cortex-amygdala and the medial prefrontal cortex-nucleus accumbens circuits, in these animal models. Using the common circuits underlying similar behavioral disruptions of social preference behaviors as an example, we highlight the importance of identifying disruption in convergent circuits to improve the translational success of animal model research for ASD treatment development.

Widespread implementations of interactive social gaze neurons in the primate prefrontal-amygdala networks.

Social gaze interaction powerfully shapes interpersonal communication. However, compared with social perception, very little is known about the neuronal underpinnings of real-life social gaze interaction. Here, we studied a large number of neurons spanning four regions in primate prefrontal-amygdala networks and demonstrate robust single-cell foundations of interactive social gaze in the orbitofrontal, dorsomedial prefrontal, and anterior cingulate cortices, in addition to the amygdala. Many neurons in these areas exhibited high temporal heterogeneity for social discriminability, with a selectivity bias for looking at a conspecific compared with an object. Notably, a large proportion of neurons in each brain region parametrically tracked the gaze of self or other, providing substrates for social gaze monitoring. Furthermore, several neurons displayed selective encoding of mutual eye contact in an agent-specific manner. These findings provide evidence of widespread implementations of interactive social gaze neurons in the primate prefrontal-amygdala networks during social gaze interaction.