Intermittent hypoxia-induced enhancements in corticospinal excitability predict gains in motor learning and metabolic efficiency.

Acute intermittent hypoxia (AIH) enhances human motor function after incomplete spinal cord injury. Although the underlying mechanisms in humans are unknown, emerging evidence indicates that AIH facilitates corticospinal excitability to the upper limb. However, the functional relevance of this plasticity remains unexplored, and it is unclear whether similar plasticity can be induced for lower limb motor areas. We recently demonstrated that AIH improves motor learning and metabolic efficiency during split-belt walking. Thus, we hypothesized that AIH increases lower limb excitability and that these enhancements would predict the magnitude of motor learning and the corresponding reductions in net metabolic power. We assessed tibialis anterior (TA) excitability using transcranial magnetic stimulation and quantified changes in spatiotemporal asymmetries and net metabolic power in response to split-belt speed perturbations. We show that AIH enhances TA excitability and that the magnitude of this facilitation positively correlates with greater spatiotemporal adaptation. Notably, we demonstrate a novel association between increased excitability and reduced net metabolic power during motor learning and savings. Together, our results suggest that AIH-induced gains in excitability predict both the magnitude of motor learning and the associated metabolic efficiency. Determining indices of AIH-induced improvements in motor performance is critical for optimizing its therapeutic reach.

How does empowering men affect intimate partner violence? Evidence from Bangladesh.

This paper investigates the relationship between women's and men's empowerment and intimate partner violence (IPV). To do so, it uses a sample of 4548 households with a husband and a wife who are present in two or three rounds of the Bangladesh Integrated Household Survey (BIHS). Measures of empowerment are constructed separately and symmetrically for husbands and wives. Conditional fixed-effects logistic regressions are employed to examine the statistical association between measures of empowerment and intimate partner violence. Findings indicate that IPV is widespread in rural Bangladesh, as 67.6% and 22.4% of households report experiencing verbal and physical IPV, respectively, in at least one round. Husbands tend to be more empowered than their wives in most, but not all, dimensions. Yet, even in dimensions of empowerment dominated by men on average, the percentage of households in which individual wives are more empowered than their husbands is notable. In regressions, some measures of men's empowerment (e.g., ownership of assets) are negatively associated with verbal and any IPV. Some measures of women's empowerment (e.g., community influence) are associated with verbal, physical, and any IPV, but the signs are mixed. All in all, the findings suggest that men's empowerment may be a determinant of intimate partner violence in rural Bangladesh, and they also underscore the need to extend theories of empowerment.

A single sequence of intermittent hypoxia does not alter stretch reflex excitability in able-bodied individuals.

Spasticity attributable to exaggerated stretch reflex pathways, particularly affecting the ankle plantar flexors, often impairs overground walking in persons with incomplete spinal cord injury. Compelling evidence from rodent models underscores how exposure to acute intermittent hypoxia (AIH) can provide a unique medium to induce spinal plasticity in key inhibitory pathways mediating stretch reflex excitability and potentially affect spasticity. In this study, we quantify the effects of a single exposure to AIH on the stretch reflex in able-bodied individuals. We hypothesized that a single sequence of AIH will increase the stretch reflex excitability of the soleus muscle during ramp-and-hold angular perturbations applied to the ankle joint while participants perform passive and volitionally matched contractions. Our results revealed that a single AIH exposure did not significantly change the stretch reflex excitability during both passive and active matching conditions. Furthermore, we found that able-bodied individuals increased their stretch reflex response from passive to active matching conditions after both sham and AIH exposures. Together, these findings suggest that a single AIH exposure might not engage inhibitory pathways sufficiently to alter stretch reflex responses in able-bodied persons. However, the generalizability of our present findings requires further examination during repetitive exposures to AIH along with potential reflex modulation during functional movements, such as overground walking.

Partial-thickness rotator cuff tears: a review of current literature on evaluation and management.

Rotator cuff disease is a common cause of shoulder pain for which partial-thickness rotator cuff tears occupy a significant proportion. Such tears are often difficult to diagnose and manage in the general clinic setting. A review of the available literature from well-known databases was performed in this study to provide a concise overview of partial-thickness rotator cuff tears to aid physicians in their understanding and management.

Conditional Astrocyte Rac1KO Attenuates Hyperreflexia after Spinal Cord Injury.

Spasticity is a hyperexcitability disorder that adversely impacts functional recovery and rehabilitative efforts after spinal cord injury (SCI). The loss of evoked rate-dependent depression (RDD) of the monosynaptic H-reflex is indicative of hyperreflexia, a physiological sign of spasticity. Given the intimate relationship between astrocytes and neurons, that is, the tripartite synapse, we hypothesized that astrocytes might have a significant role in post-injury hyperreflexia and plasticity of neighboring neuronal synaptic dendritic spines. Here, we investigated the effect of selective Rac1KO in astrocytes (i.e., adult male and female mice, transgenic cre-flox system) on SCI-induced spasticity. Three weeks after a mild contusion SCI, control Rac1wt animals displayed a loss of H-reflex RDD, that is, hyperreflexia. In contrast, transgenic animals with astrocytic Rac1KO demonstrated near-normal H-reflex RDD similar to pre-injury levels. Reduced hyperreflexia in astrocytic Rac1KO animals was accompanied by a loss of thin-shaped dendritic spine density on α-motor neurons in the ventral horn. In SCI-Rac1wt animals, as expected, we observed the development of dendritic spine dysgenesis on α-motor neurons associated with spasticity. As compared with WT animals, SCI animals with astrocytic Rac1KO expressed increased levels of the glial-specific glutamate transporter, glutamate transporter-1 in the ventral spinal cord, potentially enhancing glutamate clearance from the synaptic cleft and reducing hyperreflexia in astrocytic Rac1KO animals. Taken together, our findings show for the first time that Rac1 activity in astrocytes can contribute to hyperreflexia underlying spasticity following SCI. These results reveal an opportunity to target cell-specific molecular regulators of H-reflex excitability to manage spasticity after SCI.Significance Statement Spinal cord injury leads to stretch reflex hyperexcitability, which underlies the clinical symptom of spasticity. This study shows for the first time that astrocytic Rac1 contributes to the development of hyperreflexia after SCI. Specifically, astrocytic Rac1KO reduced SCI-related H-reflex hyperexcitability, decreased dendritic spine dysgenesis on α-motor neurons, and elevated the expression of the astrocytic glutamate transporter-1 (GLT-1). Overall, this study supports a distinct role for astrocytic Rac1 signaling within the spinal reflex circuit and the development of SCI-related spasticity.

Large volume subcutaneous delivery using multi-orifice jet injection.

Needle-free jet injection is an alternative drug delivery technique that uses the liquid drug itself to penetrate through the skin. This technology is not only a promising alternative to hypodermic needles but also has the potential to replace intravenous delivery with rapid, needle-free subcutaneous delivery for large-volume treatments. In this work we propose a parallelised, 'multi-orifice' approach to overcome the volume constraints of subcutaneous tissue. We present a prototype multi-orifice nozzle with up to seven orifices and use this nozzle to perform injections into samples of ex vivo porcine tissue. These injections demonstrated the rapid (<0.15 s) delivery of up to 2 mL into the tissue using both three and seven orifices. Delivery success (measured as the percentage of fluid deposited in the tissue relative to the total volume that left the device) was very similar when using three versus seven injection orifices. A computational fluid dynamic model of multi-orifice jet injection is also presented. This model predicts that jet production is largely unaffected as the spacing between orifices is changed from 3 mm to 48 mm. This finding is supported by measurements of the speed, volume, and shape of the jets produced by the prototype nozzle that showed very similar jets were produced through all seven orifices. These findings demonstrate the feasibility of multi-orifice jet injection for needle-free delivery of large volumes. This promising technique has the potential to improve patient experience and reduce healthcare costs in large volume parenteral delivery applications.

Rotatable Orifice for Needle-Free Jet Injection.

This research explores a new development in orifice technology for needle-free jet injection. The premise lies in the ability to control the angle at which the drug is delivered into the tissue to increase the lateral dispersion of the drug. Towards this aim, a spherical orifice that can rotate to adjust the injection angle is explored. This work tests the design and feasibility of the spherical orifice, its housing, and the orifice seats. The results show that the most successful way to create a fluid seal within the housing was to use an o-ring to create a fluid seal at the inlet side of the sphere and an extended brass seat on the outlet side of the sphere. This allowed jet speeds up to approximately 123 m/s through a 0.2 mm orifice machined into 9.5 mm diameter brass sphere. Jet speeds large enough to penetrate porcine tissue were reached at jet angles of 0° to 50° relative to the base of the injector. Although the jets successfully penetrated the tissue, the amount of fluid delivered varied depending on the injection angle. With a shallow angle injection, the fluid retention rate (the percentage of the ejected fluid from the injector which the tissue sample retained) was on average 44%. When the spherical orifice was at its maximum angle, the injection achieved an average fluid retention rate of 22%. At its widest angle, lateral dispersion of the drug also increased by approximately 40%, in comparison to conventional needles and traditional perpendicular jet injection. In summary, a spherical orifice needle-free injection system successfully produced high-speed jets and delivered liquid into porcine tissue at injection angles from 0° to 50°, demonstrating the feasibility of this technique that offers unique advantages over typical orifice plates and conventional needles.Clinical Relevance-A rotatable nozzle can be used to control the angle of needle-free drug delivery.

Enhanced motor learning and motor savings after acute intermittent hypoxia are associated with a reduction in metabolic cost.

Breathing mild bouts of low oxygen air (i.e. acute intermittent hypoxia, AIH) has been shown to improve locomotor function in humans after a spinal cord injury. How AIH-induced gains in motor performance are achieved remains unclear. We examined the hypothesis that AIH augments motor learning and motor retention during a locomotor adaptation task. We further hypothesized that gains in motor learning and retention will be associated with reductions in net metabolic power, consistent with the acquisition of energetically favourable mechanics. Thirty healthy individuals were randomly allocated into either a control group or an AIH group. We utilized a split-belt treadmill to characterize adaptations to an unexpected belt speed perturbation of equal magnitude during an initial exposure and a second exposure. Adaptation was characterized by changes in spatiotemporal step asymmetry, anterior-posterior force asymmetry, and net metabolic power. While both groups adapted by reducing spatial asymmetry, only the AIH group achieved significant reductions in double support time asymmetry and propulsive force asymmetry during both the initial and the second exposures to the belt speed perturbation. Net metabolic power was also significantly lower in the AIH group, with significant reductions from the initial perturbation exposure to the second. These results provide the first evidence that AIH mediates improvements in both motor learning and retention. Further, our results suggest that reductions in net metabolic power continue to be optimized upon subsequent learning and are driven by more energetically favourable temporal coordination strategies. Our observation that AIH facilitates motor learning and retention can be leveraged to design rehabilitation interventions that promote functional recovery. KEY POINTS: Brief exposures to low oxygen air, known as acute intermittent hypoxia (AIH), improves locomotor function in humans after a spinal cord injury, but it remains unclear how gains in motor performance are achieved. In this study, we tested the hypothesis that AIH induces enhancements in motor learning and retention by quantifying changes in interlimb coordination, anterior-posterior force symmetry and metabolic cost during a locomotor adaptation task. We show the first evidence that AIH improves both motor learning and savings of newly learned temporal interlimb coordination strategies and force asymmetry compared to untreated individuals. We further demonstrate that AIH elicits greater reductions in metabolic cost during motor learning that continues to be optimized upon subsequent learning. Our findings suggest that AIH-induced gains in locomotor performance are facilitated by enhancements in motor learning and retention of more energetically favourable coordination strategies.

Increased astrocytic GLT-1 expression in tripartite synapses is associated with SCI-induced hyperreflexia.

Spasticity is a chronic neurological complication associated with spinal cord injury (SCI), characterized by increased muscle tone and stiffness. A physiological sign of spasticity is hyperreflexia, evident by the loss of evoked rate-dependent depression (RDD) in the H-reflex. Although previous work has shown that SCI-induced astrogliosis contributes to hyperexcitability disorders, including neuropathic pain and spasticity, it is unclear how reactive astrocytes can modulate synaptic transmission within the injured spinal cord. To study astrocytes' role in post-SCI hyperreflexia, we examined glutamate transporter-1 (GLT-1) and postsynaptic density protein 95 (PSD-95) proteins in astrocytes and neurons, respectively, within the ventral horn (lamina IX) below the level of injury (spinal segment L4-5). The close juxtaposition of GLT-1 and PSD-95 markers is a molecular correlate of tripartite synapses and is thought to be a key element in the astrocyte-induced plasticity of neuronal synapses. Our study compared animals with and without SCI-induced hyperreflexia and spasticity and investigated potential synaptic abnormalities associated with astrocyte involvement. As expected, 4 wk after SCI, we observed a loss in evoked H-reflex RDD in hindlimb electromyogram recordings, i.e., hyperreflexia, in contrast to uninjured sham. Importantly, our main findings show a significant increase in the presence of GLT-1-PSD-95 tripartite synapses in the ventral spinal cord motor regions of animals exhibiting SCI-induced hyperreflexia. Taken together, our study suggests the involvement of astrocyte-neuron synaptic complexes in the plasticity-driven progression of chronic spasticity.NEW & NOTEWORTHY The role of astrocytes in H-reflex hyperexcitability following SCI remains understudied. Our findings establish a relationship between GLT-1 expression, its proximity to neuronal PSD-95 in the spinal cord ventral horn, and the loss of H-reflex RDD, i.e., hyperreflexia. Our findings provide a new perspective on synaptic alterations and the development of SCI-related spasticity.

Both Adjustable and Fixed Loop Hamstring Tendon Graft Fixation Have Similar Clinical and Patient-Reported Outcomes in Anterior Cruciate Ligament Reconstruction.

Purpose: This study aims to compare the outcomes of fixed-loop device (FLD) vs adjustable-loop device (ALD) graft fixation with up to 2-year follow-up in patients undergoing primary anterior cruciate ligament reconstruction (ACLR) in a predominantly Asian setting. Methods: Prospectively collected outcome measures as well as clinical records of patients who underwent primary ACLR using either FLD or ALD fixation of hamstring tendon autograft performed by a single surgeon were reviewed. The surgeon in this study used a fixed-loop device from 2018 to 2019 and then changed to adjustable loop from 2019 to 2020. Suspensory fixation was performed on the femoral side, and aperture (interference screw) fixation was performed on the tibial side. Outcome measures included knee range of motion, KT-1000 arthrometer testing, Lysholm knee score, and Tegner activity scale. Patients were assessed preoperatively and postoperatively at regular intervals of 6, 12, and 24 months. Results: A total of 105 patients were identified. Forty-six were excluded due to incomplete follow-up data, so 59 patients with full 2-year follow-up were included in the final study group. Both groups (FLD vs ALD) were similar in demographics except for age (P = .042). Out of 105, there were 59 patients remaining in the study group with 2-year follow-up data. No significant differences were observed between the 2 groups at all respective testing intervals. Conclusions: FLDs and ALDs for suspensory fixation of hamstring tendon autograft in ACLR had similar clinical outcomes with a minimum of 2-year follow up. There is no evidence of graft loosening from loop lengthening. Level of Evidence: Level III, retrospective comparative trial.

Acute hospital-community hospital care bundle for elderly orthopedic surgery patients: A propensity score-matched economic analysis.

BACKGROUND: While Singapore attains good health outcomes, Singapore's healthcare system is confronted with bed shortages and prolonged stays for elderly people recovering from surgery in acute hospitals. An Acute Hospital-Community Hospital (AH-CH) care bundle has been developed to assist patients in postoperative rehabilitation. The core concept is to transfer patients out of AHs when clinically recommended and into CHs, where they can receive more beneficial dedicated care to aid in their recovery, while freeing up bed capacities in AHs. AIM: To analyze the AH length of stay (LOS), costs, and savings associated with the AH-CH care bundle intervention initiated and implemented in elderly patients aged 75 years and above undergoing elective orthopedic surgery. METHODS: A total of 862 1:1 propensity score-matched patients aged 75 years and above who underwent elective orthopedic surgery in Singapore General Hospital (SGH) before (2017-2018) and after (2019-2021) the care bundle intervention period was analyzed. Outcome measures were AH LOS, CH LOS, hospitalization metrics, postoperative 30-d mortality, and modified Barthel Index (MBI) scores. The costs of AH inpatient hospital stay in the matched cohorts were compared using cost data in Singapore dollars. RESULTS: Of the 862 matched elderly patients undergoing elective orthopedic surgery before and after the care bundle intervention, the age distribution, sex, American Society of Anesthesiologists classification, Charlson Comorbidity Index, and surgical approach were comparable between both groups. Patients transferred to CHs after the surgery had a shorter median AH LOS (7 d vs 9 d, P < 0.001). The mean total AH inpatient cost per patient was 14.9% less for the elderly group transferred to CHs (S$24497.3 vs S$28772.8, P < 0.001). The overall AH U-turn rates for elderly patients within the care bundle were low, with a 0% mortality rate following orthopedic surgery. When elderly patients were discharged from CHs, their MBI scores increased significantly (50.9 vs 71.9, P < 0.001). CONCLUSION: The AH-CH care bundle initiated and implemented in the Department of Orthopedic Surgery appears to be effective and cost-saving for SGH. Our results indicate that transitioning care between acute and community hospitals using this care bundle effectively reduces AH LOS in elderly patients receiving orthopedic surgery. Collaboration between acute and community care providers can assist in closing the care delivery gap and enhancing service quality.

nELISA: A high-throughput, high-plex platform enables quantitative profiling of the secretome.

We present the nELISA, a high-throughput, high-fidelity, and high-plex protein profiling platform. DNA oligonucleotides are used to pre-assemble antibody pairs on spectrally encoded microparticles and perform displacement-mediated detection. Spatial separation between non-cognate antibodies prevents the rise of reagent-driven cross-reactivity, while read-out is performed cost-efficiently and at high-throughput using flow cytometry. We assembled an inflammatory panel of 191 targets that were multiplexed without cross-reactivity or impact on performance vs 1-plex signals, with sensitivities as low as 0.1pg/mL and measurements spanning 7 orders of magnitude. We then performed a large-scale secretome perturbation screen of peripheral blood mononuclear cells (PBMCs), with cytokines as both perturbagens and read-outs, measuring 7,392 samples and generating ~1.5M protein datapoints in under a week, a significant advance in throughput compared to other highly multiplexed immunoassays. We uncovered 447 significant cytokine responses, including multiple putatively novel ones, that were conserved across donors and stimulation conditions. We also validated the nELISA's use in phenotypic screening, and propose its application to drug discovery.

Conflicting signals: Exploring the socioeconomic implications of gender discordant names.

We investigate the educational and employment consequences of having a gender discordant name - one that is also given to people of a different gender. People with discordant names may be more likely to experience stigma due to the conflicting signal between their gender and the perceptions of femininity or masculinity associated with their names. Our primary measure of discordance is based on the percentage of men and women with each first name, using a large administrative dataset from Brazil. We find that both men and women with gender discordant names attain significantly less education. Gender discordant names are also negatively and significantly associated with earnings though, after controlling for educational attainment, only people with the most discordant names have significantly lower earnings. These results are corroborated when using crowd-sourced gender perceptions of names in our dataset, which suggests that stereotypes and the judgments of others are a probable mechanism for the observed disparities.

Dendritic Spines and Pain Memory.

Neuropathic pain is a debilitating form of pain arising from injury or disease of the nervous system that affects millions of people worldwide. Despite its prevalence, the underlying mechanisms of neuropathic pain are still not fully understood. Dendritic spines are small protrusions on the surface of neurons that play an important role in synaptic transmission. Recent studies have shown that dendritic spines reorganize in the superficial and deeper laminae of the spinal cord dorsal horn with the development of neuropathic pain in multiple models of disease or injury. Given the importance of dendritic spines in synaptic transmission, it is possible that studying dendritic spines could lead to new therapeutic approaches for managing intractable pain. In this review article, we highlight the emergent role of dendritic spines in neuropathic pain, as well as discuss the potential for studying dendritic spines for the development of new therapeutics.

Late Free Flap Failure in Head and Neck Reconstruction: Unusual Etiology in Two Case Studies and Literature Review.

The development of modern microvascular surgical techniques has enabled the reliable transfer of free vascularized tissue. This allowed for predictable reconstruction outcomes with excellent surgical success rates. However, devastating consequences of partial or total flap failure and subsequent loss may occur. This usually occurs in the first 48-72 h post-operatively. It is rare for flaps to fail in the late post-operative period and it remains poorly understood why flaps fail after day seven. We presented two patients in whom flap failure occurred after the seventh post-operative day (POD). Complete flap failure occurred after POD 9 and 27 in our cases. During the postoperative period, there was no evidence of early occlusion or insult to the vascular integrity such as venous/arterial compression. The cause of late flap failure was due to thrombophlebitis secondary to infection from the tracheostomy-neck fistula. This assumption was supported by recurrent failure of anastomoses revision.

Spatiotemporal patterns of lung disease in China before 2019: A brief analysis of two nationally representative surveys.

Little is publicly known about the conditions surrounding the emergence of COVID in China. Using two nationally representative datasets, the China Family Panel Studies (CFPS) and the China Health and Retirement Longitudinal Study (CHARLS), we engage in a descriptive analysis of spatiotemporal patterns of lung and other diseases before 2019. In both datasets, the incidence of lung disease in 2018 was elevated in Hubei province relative to other provinces. The incidence of psychiatric and nervous system disease was elevated as well. Overall, the evidence is consistent with many possible explanations. One conjecture is that there was an outbreak of influenza in central China, which implies the conditions that increased the susceptibility to influenza also facilitated the later spread of COVID. Another conjecture, though less likely, is that COVID was circulating at low levels in the population in central China during 2018. This study calls for more investigation to understand the conditions surrounding the emergence of COVID.

A Wearable Mixed Reality Platform to Augment Overground Walking: A Feasibility Study.

Humans routinely modify their walking speed to adapt to functional goals and physical demands. However, damage to the central nervous system (CNS) often results in abnormal modulation of walking speed and increased risk of falls. There is considerable interest in treatment modalities that can provide safe and salient training opportunities, feedback about walking performance, and that may augment less reliable sensory feedback within the CNS after injury or disease. Fully immersive virtual reality technologies show benefits in boosting training-related gains in walking performance; however, they lack views of the real world that may limit functional carryover. Augmented reality and mixed reality head-mount displays (MR-HMD) provide partially immersive environments to extend the virtual reality benefits of interacting with virtual objects but within an unobstructed view of the real world. Despite this potential advantage, the feasibility of using MR-HMD visual feedback to promote goal-directed changes in overground walking speed remains unclear. Thus, we developed and evaluated a novel mixed reality application using the Microsoft HoloLens MR-HMD that provided real-time walking speed targets and augmented visual feedback during overground walking. We tested the application in a group of adults not living with disability and examined if they could use the targets and visual feedback to walk at 85%, 100%, and 115% of each individual's self-selected speed. We examined whether individuals were able to meet each target gait speed and explored differences in accuracy across repeated trials and at the different speeds. Additionally, given the importance of task-specificity to therapeutic interventions, we examined if walking speed adjustment strategies were consistent with those observed during usual overground walking, and if walking with the MR-HMD resulted in increased variability in gait parameters. Overall, participants matched their overground walking speed to the target speed of the MR-HMD visual feedback conditions (all p-values > 0.05). The percent inaccuracy was approximately 5% across all speed matching conditions and remained consistent across walking trials after the first overall walking trial. Walking with the MR-HMD did not result in more variability in walking speed, however, we observed more variability in stride length and time when walking with feedback from the MR-HMD compared to walking without feedback. The findings offer support for mixed reality-based visual feedback as a method to provoke goal-specific changes in overground walking behavior. Further studies are necessary to determine the clinical safety and efficacy of this MR-HMD technology to provide extrinsic sensory feedback in combination with traditional treatments in rehabilitation.

Examining Ethnicity: Patterns of Minority Identification Among Children of Interethnic Marriages in China.

Ethnic identity is a highly contested issue in China. Yet, the literature on the social construction of ethnoracial identity is dominated by research on the Americas. In this study, we investigate patterns of ethnic identification among children of interethnic parents in China using census data from 2000 and survey data from 2010-2018. We focus on children who are aged 20 or younger and have one parent identified as an ethnic minority and one parent identified as an ethnic Han. We find that the strongest predictor of a child's minority identification is the father's ethnicity. Minority identification is also associated with gender, birth year, mother's education, household income, migration status, parent's perception of the child's diligence, the geographic concentration of minorities, and eligibility for ethnicity-based bonus points on the college entrance examination. Taken together, the results suggest that children's ethnoracial identity is shaped by family demographic characteristics as well as by education policy.

Pareto-Optimal Clustering with the Primal Deterministic Information Bottleneck.

At the heart of both lossy compression and clustering is a trade-off between the fidelity and size of the learned representation. Our goal is to map out and study the Pareto frontier that quantifies this trade-off. We focus on the optimization of the Deterministic Information Bottleneck (DIB) objective over the space of hard clusterings. To this end, we introduce the primal DIB problem, which we show results in a much richer frontier than its previously studied Lagrangian relaxation when optimized over discrete search spaces. We present an algorithm for mapping out the Pareto frontier of the primal DIB trade-off that is also applicable to other two-objective clustering problems. We study general properties of the Pareto frontier, and we give both analytic and numerical evidence for logarithmic sparsity of the frontier in general. We provide evidence that our algorithm has polynomial scaling despite the super-exponential search space, and additionally, we propose a modification to the algorithm that can be used where sampling noise is expected to be significant. Finally, we use our algorithm to map the DIB frontier of three different tasks: compressing the English alphabet, extracting informative color classes from natural images, and compressing a group theory-inspired dataset, revealing interesting features of frontier, and demonstrating how the structure of the frontier can be used for model selection with a focus on points previously hidden by the cloak of the convex hull.

Different Excitation-Inhibition Correlations Between Spontaneous and Tone-evoked Activity in Primary Auditory Cortex Neurons.

Tone-evoked synaptic excitation and inhibition are highly correlated in many neurons with V-shaped tuning curves in the primary auditory cortex of pentobarbital-anesthetized rats. In contrast, there is less correlation between spontaneous excitation and inhibition in visual cortex neurons under the same anesthetic conditions. However, it was not known whether the primary auditory cortex resembles visual cortex in having spontaneous excitation and inhibition that is less correlated than tone-evoked excitation and inhibition. Here we report whole-cell voltage-clamp measurements of spontaneous excitation and inhibition in primary auditory cortex neurons of pentobarbital-anesthetized rats. Spontaneous excitatory and inhibitory currents appeared to mainly consist of distinct events, with the inhibitory event rate typically lower than the excitatory event rate. We use the ratio of the excitatory event rate to the inhibitory event rate, and the assumption that the excitatory and inhibitory synaptic currents can each be reasonably described as a filtered Poisson process, to estimate the maximum spontaneous excitatory-inhibitory correlation for each neuron. In a subset of neurons, we also measured tone-evoked excitation and inhibition. In neurons with V-shaped tuning curves, although tone-evoked excitation and inhibition were highly correlated, the spontaneous inhibitory event rate was typically sufficiently lower than the spontaneous excitatory event rate to indicate a lower excitatory-inhibitory correlation for spontaneous activity than for tone-evoked responses.