Somatostatin-Expressing Interneurons in the Auditory Cortex Mediate Sustained Suppression by Spectral Surround.

Sensory systems integrate multiple stimulus features to generate coherent percepts. Spectral surround suppression, the phenomenon by which sound-evoked responses of auditory neurons are suppressed by stimuli outside their receptive field, is an example of this integration taking place in the auditory system. While this form of global integration is commonly observed in auditory cortical neurons, and potentially used by the nervous system to separate signals from noise, the mechanisms that underlie this suppression of activity are not well understood. We evaluated the contributions to spectral surround suppression of the two most common inhibitory cell types in the cortex, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, in mice of both sexes. We found that inactivating SOM+ cells, but not PV+ cells, significantly reduces sustained spectral surround suppression in excitatory cells, indicating a dominant causal role for SOM+ cells in the integration of information across multiple frequencies. The similarity of these results to those from other sensory cortices provides evidence of common mechanisms across the cerebral cortex for generating global percepts from separate features.SIGNIFICANCE STATEMENT To generate coherent percepts, sensory systems integrate simultaneously occurring features of a stimulus, yet the mechanisms by which this integration occurs are not fully understood. Our results show that neurochemically distinct neuronal subtypes in the primary auditory cortex have different contributions to the integration of different frequency components of an acoustic stimulus. Together with findings from other sensory cortices, our results provide evidence of a common mechanism for cortical computations used for global integration of stimulus features.

Auditory Thalamostriatal and Corticostriatal Pathways Convey Complementary Information about Sound Features.

Multiple parallel neural pathways link sound-related signals to behavioral responses. For instance, the striatum, a brain structure involved in action selection and reward-related learning, receives neuronal projections from both the auditory thalamus and auditory cortex. It is not clear whether sound information that reaches the striatum through these two pathways is redundant or complementary. We used an optogenetic approach in awake mice of both sexes to identify thalamostriatal and corticostriatal neurons during extracellular recordings, and characterized neural responses evoked by sounds of different frequencies and amplitude modulation rates. We found that neurons in both pathways encode sound frequency with similar fidelity, but display different coding strategies for amplitude modulated noise. Whereas corticostriatal neurons provide a more accurate representation of amplitude modulation rate in their overall firing rate, thalamostriatal neurons convey information about the precise timing of acoustic events. These results demonstrate that auditory thalamus and auditory cortex neurons provide complementary information to the striatum, and suggest that these pathways could be differentially recruited depending on the requirements of a sound-driven behavior.SIGNIFICANCE STATEMENT Sensory signals from the cerebral cortex and the thalamus converge onto the striatum, a nucleus implicated in reward-related learning. It is not clear whether these two sensory inputs convey redundant or complementary information. By characterizing the sound-evoked responses of thalamostriatal and corticostriatal neurons, our work demonstrates that these neural pathways convey complementary information about the temporal features of sounds. This work opens new avenues for investigating how these pathways could be selectively recruited depending on task demands, and provides a framework for studying convergence of cortical and thalamic information onto the striatum in other sensory systems.

Choice-Selective Neurons in the Auditory Cortex and in Its Striatal Target Encode Reward Expectation.

Learned behavioral responses to sounds depend largely on the expected outcomes associated with each potential choice. Where and how the nervous system integrates expectations about reward with auditory sensory information to drive appropriate decisions is not fully understood. Using a two-alternative choice task in which the expected reward associated with each sound varied over time, we investigated potential sites along the corticostriatal pathway for the integration of sound signals, behavioral choice, and reward information in male mice. We found that auditory cortical neurons encode not only sound identity, but also the animal's choice and the expected size of reward. This influence of reward expectation on sound- and choice-related activity was further enhanced in the major striatal target of the auditory cortex: the posterior tail of the dorsal striatum. These results indicate that choice-specific information is integrated with reward signals throughout the corticostriatal pathway, potentially contributing to adaptation in sound-driven behavior.SIGNIFICANCE STATEMENT Learning and maintenance of sensory-motor associations require that neural circuits keep track of sensory stimuli, choices, and outcomes. It is not clear at what stages along the auditory sensorimotor pathway these signals are integrated to influence future behavior in response to sounds. Our results show that the activity of auditory cortical neurons and of their striatal targets encodes the animals' choices and expectation of reward, in addition to stimulus identity. These results challenge previous views of the influence of motor signals on auditory circuits and identifies potential loci for integration of task-related information necessary for updating auditory decisions in changing environments.

Auditory thalamus and auditory cortex are equally modulated by context during flexible categorization of sounds.

In a dynamic world, animals must adapt rapidly to changes in the meaning of environmental cues. Such changes can influence the neural representation of sensory stimuli. Previous studies have shown that associating a stimulus with a reward or punishment can modulate neural activity in the auditory cortex (AC) and its thalamic input, the medial geniculate body (MGB). However, it is not known whether changes in stimulus-action associations alone can also modulate neural responses in these areas. We designed a categorization task for rats in which the boundary that separated low- from high-frequency sounds varied several times within a behavioral session, thus allowing us to manipulate the action associated with some sounds without changing the associated reward. We developed a computational model that accounted for the rats' performance and compared predictions from this model with sound-evoked responses from single neurons in AC and MGB in animals performing this task. We found that the responses of 15% of AC neurons and 16% of MGB neurons were modulated by changes in stimulus-action association and that the magnitude of the modulation was comparable between the two brain areas. Our results suggest that the AC and thalamus play only a limited role in mediating changes in associations between acoustic stimuli and behavioral responses.

Adaptive categorization of sound frequency does not require the auditory cortex in rats.

A defining feature of adaptive behavior is our ability to change the way we interpret sensory stimuli depending on context. Rapid adaptation in behavior has been attributed to frontal cortical circuits, but it is not clear if sensory cortexes also play an essential role in such tasks. In this study we tested whether the auditory cortex was necessary for rapid adaptation in the interpretation of sounds. We used a two-alternative choice sound-categorization task for rats in which the boundary that separated two acoustic categories changed several times within a behavioral session. These shifts in the boundary resulted in changes in the rewarded action for a subset of stimuli. We found that extensive lesions of the auditory cortex did not impair the ability of rats to switch between categorization contingencies and sound discrimination performance was minimally impaired. Similar results were obtained after reversible inactivation of the auditory cortex with muscimol. In contrast, lesions of the auditory thalamus largely impaired discrimination performance and, as a result, the ability to modify behavior across contingencies. Thalamic lesions did not impair performance of a visual discrimination task, indicating that the effects were specific to audition and not to motor preparation or execution. These results suggest that subcortical outputs of the auditory thalamus can mediate rapid adaptation in the interpretation of sounds.

[Factors associated with contacting HIV/AIDS associations in Ecuador: results of a community study]. / Factores asociados a establecer contacto con asociaciones de lucha contra el VIH/sida en Ecuador: resultados de un estudio comunitario.

OBJECTIVE: To describe the profile of people living with HIV/AIDS (PLHA) who contact HIV/AIDS associations in Ecuador and to identify the factors related to that contact. METHODS: In 2011, a cross-sectional community study was conducted in two hospitals in Guayaquil. Based on a 125-question survey administered to 300 adult PLHA, a weighted multivariate regression analysis was performed to identify the factors related to contact with an association RESULTS: Of the 300 participants, 34 (11.3%) were in contact with an association. Being over the age of 35, scoring high on the self-efficacy scale, having suffered serious social consequences after disclosing their HIV status, being able to talk to friends about living with HIV, expressing the need to talk about living with HIV with a health professional, and scoring low on the index of the HIV status disclosure control effort were related to that contact. CONCLUSIONS: The characteristics of the PLHA in contact with an association were: being over the age of 35, having suffered serious social consequences following disclosure of seropositivity, and feeling that their psychosocial needs were not being met by the health system in terms of the services provided. These people more easily managed their HIV status in their social milieu and displayed a greater ability to talk to friends about their seropositivity. This information is useful for community actors to maintain and support mobilization on HIV in Ecuador.

Subcostal transversus abdominis plane phenol injection for abdominal wall cancer pain.

A subcostal transversus abdominis plane (TAP) phenol injection was performed on a patient with refractory cancer pain due a metastatic involvement of the abdominal wall. A diagnostic block with local anesthetic was performed under ultrasound guidance (USG), resulting in a decrease of 80% and 100% in dynamic and static visual analog scale (VAS) for pain, respectively, for 20 hours. A phenol injection was then performed under USG. The patient reported 70% and 100% reduction in the dynamic and static VAS for pain and had a 50% decrease in the opioid requirement that was maintained for 2 months. TAP blocks offer an interesting tool for either diagnosis or therapeutic purpose in chronic pain management. USG provides an optimal approach to soft-tissue lesions where fluoroscopy techniques are not useful.

Selectivity to acoustic features of human speech in the auditory cortex of the mouse.

A better understanding of the neural mechanisms of speech processing can have a major impact in the development of strategies for language learning and in addressing disorders that affect speech comprehension. Technical limitations in research with human subjects hinder a comprehensive exploration of these processes, making animal models essential for advancing the characterization of how neural circuits make speech perception possible. Here, we investigated the mouse as a model organism for studying speech processing and explored whether distinct regions of the mouse auditory cortex are sensitive to specific acoustic features of speech. We found that mice can learn to categorize frequency-shifted human speech sounds based on differences in formant transitions (FT) and voice onset time (VOT). Moreover, neurons across various auditory cortical regions were selective to these speech features, with a higher proportion of speech-selective neurons in the dorso-posterior region. Last, many of these neurons displayed mixed-selectivity for both features, an attribute that was most common in dorsal regions of the auditory cortex. Our results demonstrate that the mouse serves as a valuable model for studying the detailed mechanisms of speech feature encoding and neural plasticity during speech-sound learning.

Robustness of traveling states in generic nonreciprocal mixtures.

Emergent nonreciprocal interactions violating Newton's third law are widespread in out-of-equilibrium systems. Phase separating mixtures with such interactions exhibit traveling states with no equilibrium counterpart. Using extensive Brownian dynamics simulations, we investigate the existence and stability of such traveling states in a generic nonreciprocal particle system. By varying a broad range of parameters including aggregate state of mixture components, diffusivity, degree of nonreciprocity, effective spatial dimension and density, we determine that traveling states do exist below the predator-prey regime, but nonetheless are only found in a narrow region of the parameter space. Our work also sheds light on the physical mechanisms for the disappearance of traveling states when relevant parameters are being varied, and has implications for a range of nonequilibrium systems including nonreciprocal phase separating mixtures, nonequilibrium pattern formation and predator-prey models.

Decision-making dynamics are predicted by arousal and uninstructed movements.

During sensory-guided behavior, an animal's decision-making dynamics unfold through sequences of distinct performance states, even while stimulus-reward contingencies remain static. Little is known about the factors that underlie these changes in task performance. We hypothesize that these decision-making dynamics can be predicted by externally observable measures, such as uninstructed movements and changes in arousal. Here, using computational modeling of visual and auditory task performance data from mice, we uncovered lawful relationships between transitions in strategic task performance states and an animal's arousal and uninstructed movements. Using hidden Markov models applied to behavioral choices during sensory discrimination tasks, we find that animals fluctuate between minutes-long optimal, sub-optimal, and disengaged performance states. Optimal state epochs are predicted by intermediate levels, and reduced variability, of pupil diameter and movement. Our results demonstrate that externally observable uninstructed behaviors can predict optimal performance states and suggest that mice regulate their arousal during optimal performance.

Passive exposure to task-relevant stimuli enhances categorization learning.

Learning to perform a perceptual decision task is generally achieved through sessions of effortful practice with feedback. Here, we investigated how passive exposure to task-relevant stimuli, which is relatively effortless and does not require feedback, influences active learning. First, we trained mice in a sound-categorization task with various schedules combining passive exposure and active training. Mice that received passive exposure exhibited faster learning, regardless of whether this exposure occurred entirely before active training or was interleaved between active sessions. We next trained neural-network models with different architectures and learning rules to perform the task. Networks that use the statistical properties of stimuli to enhance separability of the data via unsupervised learning during passive exposure provided the best account of the behavioral observations. We further found that, during interleaved schedules, there is an increased alignment between weight updates from passive exposure and active training, such that a few interleaved sessions can be as effective as schedules with long periods of passive exposure before active training, consistent with our behavioral observations. These results provide key insights for the design of efficient training schedules that combine active learning and passive exposure in both natural and artificial systems.

Epidural Hematoma Associated with Red Clover Use After Epidural Injection: A Case Report.

An epidural hematoma is a rare but devastating complication after interventional pain procedures. The etiology is multifactorial, including anatomical variations, inherited coagulation disorders, and consumption of anticoagulants or antiplatelet substances. Specifically, in regard to platelet aggregation, the consumption of herbal medicine is often forgotten as a potential cause for coagulation profile disorders, potentially leading to an epidural hematoma. We present the case of a patient who developed an epidural hematoma after a cervical epidural block, most likely associated with daily "red clover" consumption.

Selectivity to acoustic features of human speech in the auditory cortex of the mouse.

A better understanding of the neural mechanisms of speech processing can have a major impact in the development of strategies for language learning and in addressing disorders that affect speech comprehension. Technical limitations in research with human subjects hinder a comprehensive exploration of these processes, making animal models essential for advancing the characterization of how neural circuits make speech perception possible. Here, we investigated the mouse as a model organism for studying speech processing and explored whether distinct regions of the mouse auditory cortex are sensitive to specific acoustic features of speech. We found that mice can learn to categorize frequency-shifted human speech sounds based on differences in formant transitions (FT) and voice onset time (VOT). Moreover, neurons across various auditory cortical regions were selective to these speech features, with a higher proportion of speech-selective neurons in the dorso-posterior region. Last, many of these neurons displayed mixed-selectivity for both features, an attribute that was most common in dorsal regions of the auditory cortex. Our results demonstrate that the mouse serves as a valuable model for studying the detailed mechanisms of speech feature encoding and neural plasticity during speech-sound learning.

Decision-making dynamics are predicted by arousal and uninstructed movements.

During sensory-guided behavior, an animal's decision-making dynamics unfold through sequences of distinct performance states, even while stimulus-reward contingencies remain static. Little is known about the factors that underlie these changes in task performance. We hypothesize that these decision-making dynamics can be predicted by externally observable measures, such as uninstructed movements and changes in arousal. Here, combining behavioral experiments in mice with computational modeling, we uncovered lawful relationships between transitions in strategic task performance states and an animal's arousal and uninstructed movements. Using hidden Markov models applied to behavioral choices during sensory discrimination tasks, we found that animals fluctuate between minutes-long optimal, sub-optimal and disengaged performance states. Optimal state epochs were predicted by intermediate levels, and reduced variability, of pupil diameter, along with reduced variability in face movements and locomotion. Our results demonstrate that externally observable uninstructed behaviors can predict optimal performance states, and suggest mice regulate their arousal during optimal performance.

Multimodal postoperative analgesia with transdermal buprenorphine is a safe option in arthroscopic rotator cuff repair.

BACKGROUND: Arthroscopic rotator cuff repairs are associated with moderate-to-severe pain. Opioids are not the first line for postsurgical pain control due to their potential misuse and side effects. Transdermal buprenorphine represents an alternative for multimodal postoperative pain control. METHODS: This was a single-centre, prospective longitudinal exploratory study of patients undergoing arthroscopic rotator cuff repairs managed with multimodal analgesia with transdermal buprenorphine. Patients were followed-up by telephone at eight time points, assessing pain levels, rescue analgesics requirement and side effects. FINDINGS: Twenty-five patients with an average age of 63.4 ± 8.2 were included. Fourteen patients were ⩾65 years. Pain levels were similar among age groups at all time points, with no pain or mild pain (visual analogue scale 1-4) in most patients. The most frequent side effects were dizziness and somnolence. CONCLUSION: Transdermal buprenorphine provided a sustained analgesic effect after an arthroscopic rotator cuff repair during the acute postsurgical period. It showed a similar safety profile among younger and older patients.

Passive exposure to task-relevant stimuli enhances categorization learning.

Learning to perform a perceptual decision task is generally achieved through sessions of effortful practice with feedback. Here, we investigated how passive exposure to task-relevant stimuli, which is relatively effortless and does not require feedback, influences active learning. First, we trained mice in a sound-categorization task with various schedules combining passive exposure and active training. Mice that received passive exposure exhibited faster learning, regardless of whether this exposure occurred entirely before active training or was interleaved between active sessions. We next trained neural-network models with different architectures and learning rules to perform the task. Networks that use the statistical properties of stimuli to enhance separability of the data via unsupervised learning during passive exposure provided the best account of the behavioral observations. We further found that, during interleaved schedules, there is an increased alignment between weight updates from passive exposure and active training, such that a few interleaved sessions can be as effective as schedules with long periods of passive exposure before active training, consistent with our behavioral observations. These results provide key insights for the design of efficient training schedules that combine active learning and passive exposure in both natural and artificial systems.

Contributions of Distinct Auditory Cortical Inhibitory Neuron Types to the Detection of Sounds in Background Noise.

The ability to separate background noise from relevant acoustic signals is essential for appropriate sound-driven behavior in natural environments. Examples of this separation are apparent in the auditory system, where neural responses to behaviorally relevant stimuli become increasingly noise invariant along the ascending auditory pathway. However, the mechanisms that underlie this reduction in responses to background noise are not well understood. To address this gap in knowledge, we first evaluated the effects of auditory cortical inactivation on mice of both sexes trained to perform a simple auditory signal-in-noise detection task and found that outputs from the auditory cortex are important for the detection of auditory stimuli in noisy environments. Next, we evaluated the contributions of the two most common cortical inhibitory cell types, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, to the perception of masked auditory stimuli. We found that inactivation of either PV+ or SOM+ cells resulted in a reduction in the ability of mice to determine the presence of auditory stimuli masked by noise. These results indicate that a disruption of auditory cortical network dynamics by either of these two types of inhibitory cells is sufficient to impair the ability to separate acoustic signals from noise.

Sound-Evoked Responses of Distinct Neuron Classes from the Tail of the Striatum.

Given its inputs from auditory structures and neuromodulatory systems, the posterior tail of the striatum is ideally positioned to influence behavioral responses to acoustic stimuli according to context and previous rewards. Results from previous studies indicate that neurons in this striatal region display selective responses to sounds. However, it is not clear whether different striatal cell classes code for distinct features of sounds or how different striatal output pathways may use acoustic information to guide behavior. Here we compared the sound-evoked responses of posterior striatal neurons that form the striatal direct pathway (and express the dopamine receptor D1) to the responses of neighboring neurons in naive mice. We achieved this via optogenetic photo-identification of D1-expressing neurons during extracellular electrophysiological recordings in awake head-fixed mice of both sexes. We found that the frequency tuning of sound-responsive direct-pathway striatal neurons is comparable with that of their sound-responsive neighbors. Moreover, we found that both populations encode amplitude-modulated sounds in a similar fashion. These results suggest that different classes of neurons in the posterior striatum of naive animals have similar access to acoustic features conveyed by the auditory system even outside the context of an auditory task.

Do Children of Patients with Bipolar Disorder have a Worse Perception of Sleep Quality?

INTRODUCTION: The offspring of bipolar parents (BO) is a high-risk population for inheriting the bipolar disorder (BD) and other early clinical manifestations, such as sleep disturbances. OBJECTIVE: To compare the presence of psychiatric disorders and sleep disturbances of BO versus offspring of control parents (OCP). METHODS: A cross-sectional analytical study was conducted that compared BO versus OCP. The participants were assessed using valid tools to determine the presence of psychiatric symptoms or disorders. The "Sleep Evaluation Questionnaire" and "School Sleep Habits Survey" were used to determine sleep characteristics and associated factors. Sleep records (7-21 days) were also obtained by using an actigraphy watch. RESULTS: A sample of 42 participants (18 BO and 24 OCP) was recruited. Differences were found in the presentation of the psychiatric disorder. The BO group showed a higher frequency of major depression disorder (MDD; P = .04) and Disruptive Mood Dysregulation Disorder (DMDD; P = .04). The OCP group showed a higher frequency of Attention Deficit and Hyperactivity Disorder (ADHD; P = .65), and Separation Anxiety Disorder (SAD; P = .46). Differences were also found in sleep by using subjective measurements. Compared to the OCP group, BO had a worse perception of quality of sleep (P = .02), a higher frequency of nightmares (P = .01), a shorter total sleep time, and a higher sleep latency. Nevertheless, no differences were found between groups in the actigraphy measurements. CONCLUSIONS: The BO group had a higher frequency of Mood Disorders, and at the same time a higher number of sleep disturbances in the subjective measurements. It is possible that there is an association between mood symptoms, sleep disturbances, and coffee intake. No differences were found in the sleep profile by using actigraphy.

High risk for psychiatric disorders in bipolar offspring. A four years prospective study.

Bipolar disorder (BD) has a large hereditary component. It is a disorder that begins in early adulthood, but about which it has been described a premorbid period preceding the onset of BD. During this herald expression psychiatric disorders and symptoms, such as depressive, manic, psychotic, anxious and others, may appear. OBJECTIVE: To determine the psychopathological profile of a Bipolar Offspring (BO) group compared with the Community Control Offspring (CCO) group, and its evolution over time, including subthreshold symptoms and mental disorders. METHODS: We conducted an observational mixed cohort study, with a prospective design. We included subjects from six to 30 years of age, from the region of Antioquia, Colombia. A total of 131 subjects from the risk group BO and 150 subjects from the CCO group were evaluated through validated psychiatric diagnostic interviews (K-SADS-PL and DIGS) at baseline and at 4 years follow up. All interviews were carried out by a staff blind to parent diagnoses. Follow-up assessment were complete in 72% of the offspring. Forty-two subjects were excluded as they surpassed the age of 30 years, and only 46 subjects were not followed (change of address or did not consent to participate). RESULTS: Compared with the CCO group, the BO group had a higher frequency of affective disorder, psychotic disorder, externalizing disorders and use of the psychoactive substances during both assessments at time 1 and 2. The magnitude of the differences between the groups increased when they reach time 2. The BO group had a greater risk for presenting subthreshold symptoms and definitive psychiatric disorders, such as affective disorders, psychotic disorders and externalizing disorders. In addition, the BO group had a younger age of onset for psychoactive substances consumption. CONCLUSION: During the follow-up period, the BO group had a higher risk of presenting mental disorders compared with the CCO group. The most relevant symptoms and disorders that could precede the onset of BD were depressive, bipolar not otherwise specified, psychotic and substance use.