Deciphering mouse brain spatial diversity via glyco-lipidomic mapping.

Gangliosides in the brain play a crucial role in modulating the integrity of vertebrate central nervous system in a region-specific manner. However, to date, a comprehensive structural elucidation of complex intact ganglioside isomers has not been achieved, resulting in the elusiveness into related molecular mechanism. Here, we present a glycolipidomic approach for isomer-specific and brain region-specific profiling of the mouse brain. Considerable region-specificity and commonality in specific group of regions are highlighted. Notably, we observe a similarity in the abundance of major isomers, GD1a and GD1b, within certain regions, which provides significant biological implications with interpretation through the lens of a theoretical retrosynthetic state-transition network. Furthermore, A glycocentric-omics approaches using gangliosides and N-glycans reveal a remarkable convergence in spatial dynamics, providing valuable insight into molecular interaction network. Collectively, this study uncovers the spatial dynamics of intact glyco-conjugates in the brain, which are relevant to regional function and accelerates the discovery of potential therapeutic targets for brain diseases.

ARNT2 controls prefrontal somatostatin interneurons mediating affective empathy.

Empathy, crucial for social interaction, is impaired across various neuropsychiatric conditions. However, the genetic and neural underpinnings of empathy variability remain elusive. By combining forward genetic mapping with transcriptome analysis, we discover that aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a key driver modulating observational fear, a basic form of affective empathy. Disrupted ARNT2 expression in the anterior cingulate cortex (ACC) reduces affect sharing in mice. Specifically, selective ARNT2 ablation in somatostatin (SST)-expressing interneurons leads to decreased pyramidal cell excitability, increased spontaneous firing, aberrant Ca2+ dynamics, and disrupted theta oscillations in the ACC, resulting in reduced vicarious freezing. We further demonstrate that ARNT2-expressing SST interneurons govern affective state discrimination, uncovering a potential mechanism by which ARNT2 polymorphisms associate with emotion recognition in humans. Our findings advance our understanding of the molecular mechanism controlling empathic capacity and highlight the neural substrates underlying social affective dysfunctions in psychiatric disorders.

Phospholipase C beta 1 in the dentate gyrus gates fear memory formation through regulation of neuronal excitability.

Memory processes rely on a molecular signaling system that balances the interplay between positive and negative modulators. Recent research has focused on identifying memory-regulating genes and their mechanisms. Phospholipase C beta 1 (PLCß1), highly expressed in the hippocampus, reportedly serves as a convergence point for signal transduction through G protein-coupled receptors. However, the detailed role of PLCß1 in memory function has not been elucidated. Here, we demonstrate that PLCß1 in the dentate gyrus functions as a memory suppressor. We reveal that mice lacking PLCß1 in the dentate gyrus exhibit a heightened fear response and impaired memory extinction, and this excessive fear response is repressed by upregulation of PLCß1 through its overexpression or activation using a newly developed optogenetic system. Last, our results demonstrate that PLCß1 overexpression partially inhibits exaggerated fear response caused by traumatic experience. Together, PLCß1 is crucial in regulating contextual fear memory formation and potentially enhancing the resilience to trauma-related conditions.

Development of a Miniaturized Mechanoacoustic Sensor for Continuous, Objective Cough Detection, Characterization and Physiologic Monitoring in Children With Cystic Fibrosis.

Cough is an important symptom in children with acute and chronic respiratory disease. Daily cough is common in Cystic Fibrosis (CF) and increased cough is a symptom of pulmonary exacerbation. To date, cough assessment is primarily subjective in clinical practice and research. Attempts to develop objective, automatic cough counting tools have faced reliability issues in noisy environments and practical barriers limiting long-term use. This single-center pilot study evaluated usability, acceptability and performance of a mechanoacoustic sensor (MAS), previously used for cough classification in adults, in 36 children with CF over brief and multi-day periods in four cohorts. Children whose health was at baseline and who had symptoms of pulmonary exacerbation were included. We trained, validated, and deployed custom deep learning algorithms for accurate cough detection and classification from other vocalization or artifacts with an overall area under the receiver-operator characteristic curve (AUROC) of 0.96 and average precision (AP) of 0.93. Child and parent feedback led to a redesign of the MAS towards a smaller, more discreet device acceptable for daily use in children. Additional improvements optimized power efficiency and data management. The MAS's ability to objectively measure cough and other physiologic signals across clinic, hospital, and home settings is demonstrated, particularly aided by an AUROC of 0.97 and AP of 0.96 for motion artifact rejection. Examples of cough frequency and physiologic parameter correlations with participant-reported outcomes and clinical measurements for individual patients are presented. The MAS is a promising tool in objective longitudinal evaluation of cough in children with CF.

A wirelessly programmable, skin-integrated thermo-haptic stimulator system for virtual reality.

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.

A Modular Soft Sensing Skin for Fast Measurement of Wing Deformation in Small Unmanned Aerial Vehicles.

Insects, bats, and small birds show outstanding flight performance even under complex atmospheric conditions, which is partially due to the ability of these natural fliers to sense and react to disturbances quickly. These biological systems often use large numbers of sensors arrayed across their bodies to detect disturbances, but previous efforts to use large arrays of sensors in engineered fliers have typically resulted in slow responses due to the need to scan and process data from the large number of sensors. To address the challenges of capturing disturbances in a large sensing array with low latency, this work proposes and demonstrates a modular soft sensing system to quickly detect disturbances in small unmanned aerial vehicles. A large array of soft strain sensors with high sensing resolution covers the entire wingspan, providing rich information on wing deformation. Owing to the modular design, decentralized computation enables the sensing system to efficiently manage sensor data, resulting in sufficiently fast sampling to capture wing dynamics while all 32 sensors embedded in the modular soft sensing skin are used. This hardware architecture also results in significantly reduced noise in the sensing system, leading to a high signal-to-noise ratio. These methods can ultimately enable fast and reliable control of both soft and rigid robotic systems using large arrays of soft sensors.

A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Progression from Early Minor Recanalization to Major Recanalization in Ruptured Intracranial Aneurysms After Successful Coil Embolization: Risk Factors and Proposal of a Novel Predicting Variable.

BACKGROUND: The risk factors for the progression from early minor recanalization to major recanalization are not well established. Herein, we evaluated ruptured intracranial aneurysms (IAs) with minor recanalization within 1 year of coiling and their progression to major recurrence. METHODS: We retrospectively reviewed our database of coiled IAs and searched for ruptured saccular IAs that were successfully embolized without residual sacs. We selected IAs with minor recanalization confirmed on radiological studies within 1 year of coil embolization. All the IA cases had a follow-up period longer than 36 months based on the radiological results. RESULTS: Minor recanalization occurred in 45 IAs within 1 year of coil embolization. Among them, 14 IAs (31.1%) progressed to major recanalization, and 31 remained stable. Progression to major recanalization was detected 12 months after minor recanalization in 2 patients, 24 months in 7 patients, and 36 months in 5 patients. Moreover, the progression to major recanalization occurred more frequently in IAs at the posterior location (P = 0.024, odds ratio 11.20) and IAs with a proportional forced area > 9 mm2 (P = 0.002, odds ratio 17.13), which was a newly proposed variable in the present study. CONCLUSIONS: Our results showed that approximately one third of the ruptured IAs with early minor recanalization after coiling progressed to major recanalization within 3 years. Physicians should focus on the progression of ruptured IAs from minor to major recanalization, especially those with a posterior circulation location and a proportional forced area >9 mm2.

Dynamic switching of neural oscillations in the prefrontal-amygdala circuit for naturalistic freeze-or-flight.

The medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) are involved in the regulation of defensive behavior under threat, but their engagement in flexible behavior shifts remains unclear. Here, we report the oscillatory activities of mPFC-BLA circuit in reaction to a naturalistic threat, created by a predatory robot in mice. Specifically, we found dynamic frequency tuning among two different theta rhythms (~5 or ~10 Hz) was accompanied by agile changes of two different defensive behaviors (freeze-or-flight). By analyzing flight trajectories, we also found that high beta (~30 Hz) is engaged in the top-down process for goal-directed flights and accompanied by a reduction in fast gamma (60 to 120 Hz, peak near 70 Hz). The elevated beta nested the fast gamma activity by its phase more strongly. Our results suggest that the mPFC-BLA circuit has a potential role in oscillatory gear shifting allowing flexible information routing for behavior switches.

Coil embolization for ruptured and unruptured very small intracranial aneurysms: A retrospective review of a 10-year single-center experience.

Because of the risk of intraoperative rupture and technical difficulties, coil embolization of very small aneurysms (VSIAs) with a diameter of ≤3 mm is challenging. Herein, we reviewed our treatment strategies and outcomes in performing coil embolization for VSIAs compared to those for larger sized intracranial aneurysms (IAs) with 4 to 4.5 mm. We retrospectively reviewed the data on ruptured and unruptured VSIAs and larger-sized IAs treated with coiling from January 2012 to June 2021. Saccular IAs treated with coil embolization and followed up for at least 6 months with imaging studies were included in the study. Fifty-eight VSIAs (27 subarachnoid hemorrhages [SAH group] and 31 unruptured hemorrhages [URA group]) were identified. The wide-necked VSIAs were significantly more common in the URA group (90.3% vs 63.0%, P = .013). Procedural complications occurred in 8 cases (13.8%): intra-procedural rupture (n = 3), coil prolapse (n = 3), and thromboembolic events (n = 2). Complications were more frequent in the SAH group (P = .020). SAH was an independent risk factor for procedural complications (odds ratio, 11.293 [95% confidence interval: 1.173-108.684], P = .036), and the outcomes were affected by SAH presentation (P = .007) and poor clinical status of SAH (P = .001). When compared with larger IAs (n = 57), there were no significant differences in treatment outcomes, procedural complications, and clinical outcomes. VSIAs ≤ 3 mm in diameter were successfully treated with coil embolization, with reasonable procedure-related complications and treatment outcomes. The safety and efficacy of coil embolization for VSIAs were comparable to those of 4 to 4.5 mm sized IAs in this single-center cohort.

Stretched and fractured Neuroform Atlas® stent during a stent­assisted coil embolization: A case report.

The Neuroform Atlas® stent is one of the most recently developed stents for coil embolization, with advancements in a lower-profile delivery system, enhanced trackability, smaller cell size, and increased wall conformability. Because of these advantages, the Neuroform Atlas® stent shows high technical success with few procedure-related complications. However, the present study reported a rare complication of a stretched and partially fractured Neuroform Atlas® stent due to unexpected partial withdrawal of microcatheter during deployment for coil embolization of an intracranial aneurysm. The measured length of the stent was ~30 mm, which was greater than the normal length (21 mm). An additional stent was inserted into the distal part of the deployed stent to stabilize the damaged stent and remodel the aneurysm neck. This complication was considered to potentially result from the combination of several factors, including: Curved vessel; open-cell stent; unexpected microcatheter withdrawal during stent deployment; and hooking of the aneurysm selecting microcatheter with stent strut. Understanding the stent design and careful manipulation while avoiding unexpected withdrawal of the microcatheter could prevent this complication.

Negative Influence of the Hunger State on Rule-observance Behavior in Mice.

Developing social strategies to share limited resources equally and maximize the long-term benefits of conflict resolution is critical for appropriate social interactions. During social interactions, social decision-making depends not only on the external environment, but also on internal factors, such as hunger, thirst, or fatigue. In particular, hunger, which is related to food as a physical need, plays a dominant role in social decision-making. However, the consequences of food deprivation on social decision-making are not well understood. We have previously shown that mice with rule-observance behavior are capable of resolving conflict during social decision-making by observing a well-established social strategy based on reward zone allocation. Here, we developed a rule-observance behavior paradigm wherein the hunger state is achieved by applying food restrictions on mice prior to social behavior experiments. We found that the hunger state in mice deteriorated the established social strategy by decreasing reaction time, implying an increase in impulsivity. In contrast, the hunger state did not affect reward zone allocation, indicating no effect on spatial memory. This decrease in reaction time led to a significant increase in the percentage of violations during rule observance and a significant decrease in the amount of reward (payoff equity). Our study proposes that the hunger state exerts a detrimental effect on appropriate social decision-making by decreasing reaction time, increasing violation, and decreasing payoff equity in rule-observance behavior.

Skin-integrated systems for power efficient, programmable thermal sensations across large body areas.

Thermal sensations contribute to our ability to perceive and explore the physical world. Reproducing these sensations in a spatiotemporally programmable manner through wireless computer control could enhance virtual experiences beyond those supported by video, audio and, increasingly, haptic inputs. Flexible, lightweight and thin devices that deliver patterns of thermal stimulation across large areas of the skin at any location of the body are of great interest in this context. Applications range from those in gaming and remote socioemotional communications, to medical therapies and physical rehabilitation. Here, we present a set of ideas that form the foundations of a skin-integrated technology for power-efficient generation of thermal sensations across the skin, with real-time, closed-loop control. The systems exploit passive cooling mechanisms, actively switchable thermal barrier interfaces, thin resistive heaters and flexible electronics configured in a pixelated layout with wireless interfaces to portable devices, the internet and cloud data infrastructure. Systematic experimental studies and simulation results explore the essential mechanisms and guide the selection of optimized choices in design. Demonstration examples with human subjects feature active thermoregulation, virtual social interactions, and sensory expansion.

Hemispherically lateralized rhythmic oscillations in the cingulate-amygdala circuit drive affective empathy in mice.

Observational fear, a form of emotional contagion, is thought to be a basic form of affective empathy. However, the neural process engaged at the specific moment when socially acquired information provokes an emotional response remains elusive. Here, we show that reciprocal projections between the anterior cingulate cortex (ACC) and basolateral amygdala (BLA) in the right hemisphere are essential for observational fear, and 5-7 Hz neural oscillations were selectively increased in those areas at the onset of observational freezing. A closed-loop disruption demonstrated the causal relationship between 5-7 Hz oscillations in the cingulo-amygdala circuit and observational fear responses. The increase/decrease in theta power induced by optogenetic manipulation of the hippocampal theta rhythm bi-directionally modulated observational fear. Together, these results indicate that hippocampus-dependent 5-7 Hz oscillations in the cingulo-amygdala circuit in the right hemisphere are the essential component of the cognitive process that drives empathic fear, but not freezing, in general.

Direct Cannulation of a Calvarial Diploic Vein for Embolization of a Symptomatic Intraosseous Arteriovenous Fistula: A Case Report.

Diploic arteriovenous fistulas (AVFs) or intraosseous dural AVFs are rare arteriovenous shunts. A diploic AVF is formed between a meningeal artery and an intraosseous diploic vein or the transosseous emissary vein, and the nidus is located exclusively within the bone. Currently, endovascular embolization with a transvenous approach is considered the treatment of choice for most dural AVFs. However, in the absence of an accessible venous channel, an alternate treatment approach should be considered. Herein, we report a case of a diploic AVF that was treated using embolization with transosseous direct cannulation.

Deletion of Phospholipase C ß1 in the Thalamic Reticular Nucleus Induces Absence Seizures.

Absence seizures are caused by abnormal synchronized oscillations in the thalamocortical (TC) circuit, which result in widespread spike-and-wave discharges (SWDs) on electroencephalography (EEG) as well as impairment of consciousness. Thalamic reticular nucleus (TRN) and TC neurons are known to interact dynamically to generate TC circuitry oscillations during SWDs. Clinical studies have suggested the association of Plcß1 with early-onset epilepsy, including absence seizures. However, the brain regions and circuit mechanisms related to the generation of absence seizures with Plcß1 deficiency are unknown. In this study, we found that loss of Plcß1 in mice caused spontaneous complex-type seizures, including convulsive and absence seizures. Importantly, TRN-specific deletion of Plcß1 led to the development of only spontaneous SWDs, and no other types of seizures were observed. Ex vivo slice patch recording demonstrated that the number of spikes, an intrinsic TRN neuronal property, was significantly reduced in both tonic and burst firing modes in the absence of Plcß1 . We conclude that the loss of Plcß1 in the TRN leads to decreased excitability and impairs normal inhibitory neuronal function, thereby disrupting feedforward inhibition of the TC circuitry, which is sufficient to cause hypersynchrony of the TC system and eventually leads to spontaneous absence seizures. Our study not only provides a novel mechanism for the induction of SWDs in Plcß1 -deficient patients but also offers guidance for the development of diagnostic and therapeutic tools for absence epilepsy.

Experience of a hierarchical relationship between a pair of mice specifically influences their affective empathy toward each other.

Prior experience of social hierarchy is known to modulate emotional contagion, a basic form of affective empathy. However, it is not known whether this behavioral effect occurs through changes in an individual's traits due to their experience of social hierarchy or specific social interrelationships between the individuals. Groups of four mice with an established in-group hierarchy were used to address this in conjunction with a tube test. The rank-1 and rank-4 mice were designated as the dominant or subordinate groups, respectively. The two individuals in between were designated as the intermediate groups, which were then used as the observers in observational fear learning (OFL) experiments, an assay for emotional contagion. The intermediate observers showed greater OFL responses to the dominant demonstrator than the subordinate demonstrators recruited from the same home-cage. When the demonstrators were strangers from different cages, the intermediate observers did not distinguish between dominant and subordinate, displaying the same level of OFL. In a reverse setting in which the intermediate group was used as the demonstrator, the subordinate observers showed higher OFL responses than the dominant observers, and this occurred only when the demonstrators were cagemates of the observers. Furthermore, the bigger the rank difference between a pair, the higher the OFL level that the observer displayed. Altogether, these results demonstrate that the hierarchical interrelationship established between a given pair of animals is critical for expressing emotional contagion between them rather than any potential changes in intrinsic traits due to the experience of dominant/subordinate hierarchy. PRACTITIONER POINTS: Subordinate observer or dominant demonstrator resulted in higher affective empathic response in familiar pairs but not unfamiliar pairs. The relative social rank of the observer with respect to the demonstrator had a negative linear correlation with the affective empathic response of the observer in familiar pairs but not unfamiliar pairs. The effect of social rank on affective empathy is attributed to the prior social hierarchical interrelationship between them and is not due to intrinsic attributes of an individual based on one's dominance rank.

Proper Head Rotation when Performing Microvascular Decompression for Hemifacial Spasm: An Orthometric Consideration Based on Preoperative MRI.

BACKGROUND: The classic surgical position for microvascular decompression (MVD) is lateral decubitus with the head rotated 10 degrees away from the affected side. In this study, we measured the angles of the posterior fossa, specifically focusing on the surgical corridors used in MVD surgery for hemifacial spasm (HFS), to identify the proper surgical position. METHOD: The following parameters were assessed on preoperative magnetic resonance images (MRI): petrous angle (PA), sigmoid angle (SA), sigmoid diameter (SD), and root exit zone-sigmoid sinus edge angle (REZ-SEA). RESULTS: The mean PA was 59.7 ± 5.6 degrees, SA was 16.8 ± 8.6 degrees, SD was 13.4 ± 3.5 mm, and the mean REZ-SEA was 59.6 ± 5.8 degrees. The difference between the maximum SA to avoid cerebellar hemisphere injury and the minimum REZ-SEA required to verify the facial nerve REZ is assumed to be the usable range of angles for the operative microscope; the average midpoint of this range was 38.2 ± 6.4 degrees. CONCLUSION: Turning the patient's head 10 degrees away from the affected side was generally appropriate for performing MVD surgery because it provided a mean microscope angle of 48 degrees. However, some patients had corner values for the sigmoid angle, REZ-SEA, and sigmoid sinus diameter. Rotating a patient's head based on precise calculations from preoperative MRI helps to achieve successful surgery.

Treatment for Hemifacial Spasm Associated with a Dissecting Vertebral Artery Aneurysm Requiring Microvascular Decompression in Addition to Endovascular Trapping: A Case Report with Literature Review.

BACKGROUND: The treatment protocol for hemifacial spasm (HFS) associated with dissecting vertebral artery aneurysm (DVAA) has not been established. CASE DESCRIPTION: A-42-year-old man with left HFS underwent endovascular trapping for a DVAA that was identified on brain imaging. Although the dissecting segment was treated successfully, the HFS persisted for 3 months, and subsequently microvascular decompression (MVD) was needed. The posteroinferior cerebellar artery (PICA) was found to be interposed between the root exit zone of the facial nerve and DVAA during surgery. After pulling out the PICA, the HFS ceased immediately. CONCLUSION: HFS associated with DVAA should be considered carefully before formulating a treatment strategy. Moreover, the cause of pulsatile compression may not be visible on brain imaging, and MVD surgery may be indicated in such cases.