A Simple 3D Printed Model for Intracranial Vascular Anastomosis Practice and the Rochester Bypass Training Score.

BACKGROUND AND OBJECTIVES: Surgical simulation models in cranial neurosurgery are needed to allow affordable, accessible, and validated practice in resident education. Current bypass anastomosis practice models revolve around basic tube tying or complex animal and 3-dimensional models. This study sought to design and validate a 3-dimensional printed model for intracranial anastomosis training. METHODS: A computer-aided design (CAD) generic skull was uploaded into Meshmixer (v.3.5), and a 55-mm opening was created on the right side, mimicking a standard orbitozygomatic craniotomy. The model was rotated 15° upward and 35° left, before a 10-mm square frame was added 80-mm deep to the right orbit. The CAD model was uploaded to GrabCAD and printed using a J750 PolyJet 3D printer before being paired with a vascular anastomosis kit. The model was validated with standardized assessments of residents and attendings by simulating an "M2 to P2" bypass. The Rochester Bypass Training Score (RBTS) was created to assess bypass patency, back wall suturing, and suture quality. Postsimulation survey data regarding the realism and usefulness of the simulation were collected. RESULTS: Five junior residents (Postgraduate Year 1-4), 3 senior residents (Postgraduate Year 5-7), and 2 attendings were participated. The mean operative time in minutes was as follows: junior residents 78, senior residents 33, and attendings 50. The RBTS means were as follows: junior residents 2.4, senior residents 4.0, and attendings 5.0. Participants agreed that the model was realistic, useful for improving operative technique, and would increase comfort in bypass procedures. There are a few different printing options, varying in model infill and printing material used. For this experiment, a mix of Vero plastics were used totaling $309.09 per model; however, using the more common printing material polylactic acid brings the cost to $17.27 for a comparable model. CONCLUSION: This study presents an affordable, realistic, and educational intracranial vascular anastomosis simulator and introduces the RBTS for assessment.

Topological Data Analysis Captures Task-Driven fMRI Profiles in Individual Participants: A Classification Pipeline Based on Persistence.

BOLD-based fMRI is the most widely used method for studying brain function. The BOLD signal while valuable, is beset with unique vulnerabilities. The most notable of these is the modest signal to noise ratio, and the relatively low temporal and spatial resolution. However, the high dimensional complexity of the BOLD signal also presents unique opportunities for functional discovery. Topological Data Analyses (TDA), a branch of mathematics optimized to search for specific classes of structure within high dimensional data may provide particularly valuable applications. In this investigation, we acquired fMRI data in the anterior cingulate cortex (ACC) using a basic motor control paradigm. Then, for each participant and each of three task conditions, fMRI signals in the ACC were summarized using two methods: a) TDA based methods of persistent homology and persistence landscapes and b) non-TDA based methods using a standard vectorization scheme. Finally, using machine learning (with support vector classifiers), classification accuracy of TDA and non-TDA vectorized data was tested across participants. In each participant, TDA-based classification out-performed the non-TDA based counterpart, suggesting that our TDA analytic pipeline better characterized task- and condition-induced structure in fMRI data in the ACC. Our results emphasize the value of TDA in characterizing task- and condition-induced structure in regional fMRI signals. In addition to providing our analytical tools for other users to emulate, we also discuss the unique role that TDA-based methods can play in the study of individual differences in the structure of functional brain signals in the healthy and the clinical brain.

Ultrasound Assessment of the Ulnar Nerve Around the Elbow and Diagnosis of Cubital Tunnel Syndrome, Clinical Outcomes.

BACKGROUND: There is increased interest in ultrasound (US) for the diagnosis of cubital tunnel syndrome (CuTS). We hypothesize that ulnar nerve cross-sectional area (CSA) correlates with disease severity and electrodiagnostic studies (EDX). METHODS: ARetrospective review was performed at a tertiary medical center. One hundred seventeen patients (166 ulnar nerves) were evaluated. Maximum CSA at 3 points around the elbow (proximal, groove, and distal) and EDX results (American Board of Electrodiagnostic Medicine-certified physiatrist's interpretations) were collected. RESULTS: US was positive (CSA > 0.1 cm2) in 95/117 cases (81.20%) versus 84/117 (71.79%) positive for EDX. CuTS patients treated surgically had significantly greater (0.13 cm2, standard deviation [SD] 0.038) preoperative CSA than non-operative patients (0.10 cm2, SD 0.033) (p = .003). CSA increased as EDX increased in severity; mild (0.116 cm2, SD 0.031), moderate (0.121 cm2, SD 0.035), and severe (0.163 cm2, SD 0.047) with a significant difference between the mild and severe groups (P = .001) and between the moderate and severe groups (p = .01). Significant differences were seen between patients with positive US and EDX studies compared to those with negative US and EDX in the average physical function scores (57.26, SD 8.57 versus 43.18, SD 7.70; p < .001); average sleep scores (50.14, SD 9.53 versus 56.62, SD 7.31; p = .02); average physical function scores (43.04, SD 8.68 versus 57.08, SD 6.34; p < .001) and average depression scores (49.10, SD 10.88 versus 45.043, SD 7.06; p = .02). CONCLUSIONS: US is a reliable tool for diagnosis and surgical decision-making for CuTS. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic/III.

Autologous breast reconstruction with latissimus dorsi flap in obese patients: Time-to-event analysis.

BACKGROUND: Obesity is a multisystem disease process that confers increased surgical risk. In patients who are not surgical candidates for breast reconstruction with implants/tissue expanders or abdomen-based flaps, the latissimus dorsi flap (LDF) remains a versatile alternative due to its safety profile. We conducted an analysis of patients who underwent reconstruction with LDFs and compared outcomes between two groups: obese and nonobese patients. METHODS: We reviewed records from patients undergoing total mastectomy and breast reconstruction with LDFs between January 2011 and December 2021. We compared the surgical outcomes between obese and nonobese patients. Associations between risk factors and the presence of wound-related complications were analyzed using multivariable Cox proportional-hazards models. RESULTS: One-hundred ten reconstructions were performed in obese patients (67.5%) and fifty-three in nonobese patients (32.5%). The median body mass index was 34.96 kg/m2 [32.6-39.2] in the obese patients' group and 26.8 kg/m2 [25.7-28.9] in the nonobese group (P < 0.001). The mean age was comparable between groups (54 years; P = 0.632). The rate of donor-site and recipient-site complications was similar between groups. The rate of revision procedures for secondary fat grafting and donor- or recipient-site revisions was comparable between obese and nonobese patients. Preoperative radiotherapy (hazard ratio [HR], 2.44), nipple-sparing mastectomy (HR, 3.26), and vertical pattern mastectomy (HR, 2.86) were associated with an increased risk of wound disruption. CONCLUSION: The LDF is a reliable and safe alternative for autologous breast reconstruction in obese patients. The rates of surgical site complications were comparable between obese and nonobese patients.

Simultaneous Furlow Palatoplasty and Tonsillectomy for the Treatment of Velopharyngeal Insufficiency and Tonsillar Hypertrophy.

OBJECTIVE: To determine whether performing tonsillectomy at the time of Furlow palatoplasty for the treatment of cleft palate related velopharyngeal insufficiency (VPI) incurs increased surgical complications or compromises speech outcomes. DESIGN: A retrospective review of patients who had Furlow palatoplasty and the outcomes of surgery in the treatment of cleft palate related VPI. SETTING: A single academic center between January 2015 and January 2022. PARTICIPANTS: Patients with submucous cleft (SMC) palate or patients with prior straight line primary palatoplasty presenting with VPI. INTERVENTIONS: Simultaneous conversion Furlow palatoplasty and tonsillectomy. MAIN OUTCOME MEASURE(S): Primary outcome measures include preoperative and postoperative Modified Pittsburgh Weighted Speech Scale (mPWSS), and postoperative surgical complications. RESULTS: Eight patients (25%) underwent Furlow palatoplasty and concomitant tonsillectomy, while 24 patients (75%) underwent Furlow palatoplasty alone. A significantly lower median postoperative mPWSS score, corresponding to better velopharyngeal function, was reported for patients in the Furlow-tonsillectomy group (0, IQR 0-0) compared to the Furlow only group (1, IQR 0-9, p = 0.046). No surgical complications were encountered in either group. Five patients (20.8%) in the Furlow only group required subsequent surgery for persistent VPI. No patients in the Furlow-tonsillectomy group required additional surgical treatment for VPI (0%, p = 0.16). CONCLUSIONS: Tonsillectomy at time of Furlow palatoplasty is utilized in patients with both VPI and baseline tonsillar hypertrophy to lessen the risk of postoperative obstructive breathing. Tonsillectomy performed concurrently with Furlow palatoplasty is safe, without increased risk of surgical complications, and does not compromise post-Furlow palatoplasty speech outcomes.

From mathematics to medicine: A practical primer on topological data analysis (TDA) and the development of related analytic tools for the functional discovery of latent structure in fMRI data.

fMRI is the preeminent method for collecting signals from the human brain in vivo, for using these signals in the service of functional discovery, and relating these discoveries to anatomical structure. Numerous computational and mathematical techniques have been deployed to extract information from the fMRI signal. Yet, the application of Topological Data Analyses (TDA) remain limited to certain sub-areas such as connectomics (that is, with summarized versions of fMRI data). While connectomics is a natural and important area of application of TDA, applications of TDA in the service of extracting structure from the (non-summarized) fMRI data itself are heretofore nonexistent. "Structure" within fMRI data is determined by dynamic fluctuations in spatially distributed signals over time, and TDA is well positioned to help researchers better characterize mass dynamics of the signal by rigorously capturing shape within it. To accurately motivate this idea, we a) survey an established method in TDA ("persistent homology") to reveal and describe how complex structures can be extracted from data sets generally, and b) describe how persistent homology can be applied specifically to fMRI data. We provide explanations for some of the mathematical underpinnings of TDA (with expository figures), building ideas in the following sequence: a) fMRI researchers can and should use TDA to extract structure from their data; b) this extraction serves an important role in the endeavor of functional discovery, and c) TDA approaches can complement other established approaches toward fMRI analyses (for which we provide examples). We also provide detailed applications of TDA to fMRI data collected using established paradigms, and offer our software pipeline for readers interested in emulating our methods. This working overview is both an inter-disciplinary synthesis of ideas (to draw researchers in TDA and fMRI toward each other) and a detailed description of methods that can motivate collaborative research.

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. OBJECTIVES: AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. RESULTS: We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. CONCLUSION: Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.

Doxorubicin-induced cardiomyocyte death is mediated by unchecked mitochondrial fission and mitophagy.

Doxorubicin (Dox) is a widely used antineoplastic agent that can cause heart failure. Dox cardiotoxicity is closely associated with mitochondrial damage. Mitochondrial fission and mitophagy are quality control mechanisms that normally help maintain a pool of healthy mitochondria. However, unchecked mitochondrial fission and mitophagy may compromise the viability of cardiomyocytes, predisposing them to cell death. Here, we tested this possibility by using Dox-treated H9c2 cardiac myoblast cells expressing either the mitochondria-targeted fluorescent protein MitoDsRed or the novel dual-fluorescent mitophagy reporter mt-Rosella. Dox induced mitochondrial fragmentation as shown by reduced form factor, aspect ratio, and mean mitochondrial size. This effect was abolished by short interference RNA-mediated knockdown of dynamin-related protein 1 (DRP1), a major regulator of fission. Importantly, DRP1 knockdown decreased cell death as indicated by the reduced number of propidium iodide-positive cells and the cleavage of caspase-3 and poly (ADP-ribose) polymerase. Moreover, DRP1-deficient mice were protected from Dox-induced cardiac damage, strongly supporting a role for DRP1-dependent mitochondrial fragmentation in Dox cardiotoxicity. In addition, Dox accelerated mitophagy flux, which was attenuated by DRP1 knockdown, as assessed by the mitophagy reporter mt-Rosella, suggesting the necessity of mitochondrial fragmentation in Dox-induced mitophagy. Knockdown of parkin, a positive regulator of mitophagy, dramatically diminished Dox-induced cell death, whereas overexpression of parkin had the opposite effect. Together, these results suggested that Dox cardiotoxicity was mediated, at least in part, by the increased mitochondrial fragmentation and accelerated mitochondrial degradation by the lysosome. Strategies that limit mitochondrial fission and mitophagy in the physiologic range may help reduce Dox cardiotoxicity.-Catanzaro, M. P., Weiner, A., Kaminaris, A., Li, C., Cai, F., Zhao, F., Kobayashi, S., Kobayashi, T., Huang, Y., Sesaki, H., Liang, Q. Doxorubicin-induced cardiomyocyte death is mediated by unchecked mitochondrial fission and mitophagy.

Incidence of Cellulitis in Lower Extremity Burns: 6-Year Analysis.

INTRODUCTION: Patients with burn wounds of the lower extremities are at increased risk of developing cellulitis. The probability of developing burn-associated cellulitis is presumed to be correlated with a medical history of diabetes, the etiology of the burn, delay in hospitalization of the patient during their initial presentation, and depth of the burn itself. This study aims to identify factors that place patients at increased risk for developing lower extremity burn wound cellulitis. MATERIALS AND METHODS: A retrospective chart review was performed of all Nassau University Medical Center Burn Center admissions from January 2010 to January 2016. All patients admitted with burns of any etiology isolated to the lower extremity were included in this study. Patients who were evaluated and followed as an outpatient were not included in this study. Pediatric patients less than or equal to 12 years of age were excluded from this study. RESULTS: Of the 218 admissions for lower extremity burns during the 6-year study period, 34% of patients developed cellulitis. Risk factors for developing lower extremity burn wound cellulitis included being male, greater depth of burn, and burn-to-admission delay. This was true in both univariate and multivariate analysis. total body surface area was a risk factor on univariate analysis but was not found to be an independent risk factor on multivariate analysis. No difference was observed in the development of cellulitis in patients discharged on oral antibiotics compared with those not given antibiotics. CONCLUSIONS: Burn wound cellulitis is the second most common complication observed in burns. Identification of patients at risk for developing cellulitis is important. Admitting these patients at increased risk and excising and grafting the burned area is a reasonable solution in preventing this costly complication.

Redefining the Rectus Sheath: Implications for Abdominal Wall Repair.

BACKGROUND: The abdominal wall is frequently manipulated in a variety of reconstructive procedures, and its anatomy is well described. The authors' clinical observations, however, contradict the standard depiction of the components of the abdominal wall at various levels-particularly regarding the course of the transversus abdominis muscle. Therefore, the authors sought to characterize the components of the rectus sheath at various surgical landmarks to define anatomic points important to abdominal wall repair. METHODS: The authors analyzed the abdominal computed tomographic studies of 100 healthy, young (age, 18 to 35 years; body mass index, 20 to 40 kg/m) patients with suspected renal calculi. Coordinates of key landmarks were recorded at vertebral levels T12 to L5 using a specially designed computer program that scaled all values and calculated distances between various points. RESULTS: All subjects had significant presence of the transversus abdominis within the rectus sheath (the overlap between the abdominis rectus and transversus abdominis muscles) at the costal margin plane (T12-L1, 4.2 cm). Ninety-nine percent had transversus abdominis presence within the rectus sheath at L1-L2 (3.2 cm), 86 percent at the level of the twelfth rib (L2-L3, 1.4 cm), 36 percent at the umbilicus (L3-L4), and 2 percent slightly above the posterosuperior iliac spine (L5-S1). CONCLUSIONS: These findings contradict classic teachings of abdominal wall structure and highlight the need for a cautious revisiting of the various permutations of component separation, particularly posterior component release. Furthermore, these anatomical landmarks may help predict the development or recurrence of ventral hernias, thus guiding patient selection and informing surgical technique.

Hindlimb movement modulates the activity of rostral fastigial nucleus neurons that process vestibular input.

Integration of vestibular and proprioceptive afferent information within the central nervous system is a critical component of postural regulation. We recently demonstrated that labyrinthine and hindlimb signals converge onto vestibular nucleus neurons, such that hindlimb movement modulates the activity of these cells. However, it is unclear whether similar convergence of hindlimb and vestibular signals also occurs upstream from the vestibular nuclei, particularly in the rostral fastigial nucleus (rFN). We tested the hypothesis that rFN neurons have similar responses to hindlimb movement as vestibular nucleus neurons. Recordings were obtained from 53 rFN neurons that responded to hindlimb movement in decerebrate cats. In contrast to vestibular nucleus neurons, which commonly encoded the direction of hindlimb movement (81 % of neurons), few rFN neurons (21 %) that responded to leg movement encoded such information. Instead, most rFN neurons responded to both limb flexion and extension. Half of the rFN neurons whose activity was modulated by hindlimb movement received convergent vestibular inputs. These results show that rFN neurons receive somatosensory inputs from the hindlimb and that a subset of rFN neurons integrates vestibular and hindlimb signals. Such rFN neurons likely perform computations that participate in maintenance of balance during upright stance and movement. Although vestibular nucleus neurons are interconnected with the rFN, the dissimilarity of responses of neurons sensitive to hindlimb movement in the two regions suggests that they play different roles in coordinating postural responses during locomotion and other movements which entail changes in limb position.

Counting the number of excited states in organic semiconductor systems using topology.

Exciton scattering theory attributes excited electronic states to standing waves in quasi-one-dimensional molecular materials by assuming a quasi-particle picture of optical excitations. The quasi-particle properties at branching centers are described by the corresponding scattering matrices. Here, we identify the topological invariant of a scattering center, referred to as its winding number, and apply topological intersection theory to count the number of quantum states in a quasi-one-dimensional system.

Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: potential contributions to motion sickness.

Vomiting and nausea can be elicited by a variety of stimuli, although there is considerable evidence that the same brainstem areas mediate these responses despite the triggering mechanism. A variety of experimental approaches showed that nucleus tractus solitarius, the dorsolateral reticular formation of the caudal medulla (lateral tegmental field), and the parabrachial nucleus play key roles in integrating signals that trigger nausea and vomiting. These brainstem areas presumably coordinate the contractions of the diaphragm and abdominal muscles that result in vomiting. However, it is unclear whether these regions also mediate the autonomic responses that precede and accompany vomiting, including alterations in gastrointestinal activity, sweating, and changes in blood flow to the skin. Recent studies showed that delivery of an emetic compound to the gastrointestinal system affects the processing of vestibular inputs in the lateral tegmental field and parabrachial nucleus, potentially altering susceptibility for vestibular-elicited vomiting. Findings from these studies suggested that multiple emetic inputs converge on the same brainstem neurons, such that delivery of one emetic stimulus affects the processing of another emetic signal. Despite the advances in understanding the neurobiology of nausea and vomiting, much is left to be learned. Additional neurophysiologic studies, particularly those conducted in conscious animals, will be crucial to discern the integrative processes in the brain stem that result in emesis.

Integration of vestibular and gastrointestinal inputs by cerebellar fastigial nucleus neurons: multisensory influences on motion sickness.

Previous studies demonstrated that ingestion of the emetic compound copper sulfate (CuSO4) alters the responses to vestibular stimulation of a large fraction of neurons in brainstem regions that mediate nausea and vomiting, thereby affecting motion sickness susceptibility. Other studies suggested that the processing of vestibular inputs by cerebellar neurons plays a critical role in generating motion sickness and that neurons in the cerebellar fastigial nucleus receive visceral inputs. These findings raised the hypothesis that stimulation of gastrointestinal receptors by a nauseogenic compound affects the processing of labyrinthine signals by fastigial nucleus neurons. We tested this hypothesis in decerebrate cats by determining the effects of intragastric injection of CuSO4 on the responses of rostral fastigial nucleus to whole-body rotations that activate labyrinthine receptors. Responses to vestibular stimulation of fastigial nucleus neurons were more complex in decerebrate cats than reported previously in conscious felines. In particular, spatiotemporal convergence responses, which reflect the convergence of vestibular inputs with different spatial and temporal properties, were more common in decerebrate than in conscious felines. The firing rate of a small percentage of fastigial nucleus neurons (15%) was altered over 50% by the administration of CuSO4; the firing rate of the majority of these cells decreased. The responses to vestibular stimulation of a majority of these cells were attenuated after the compound was provided. Although these data support our hypothesis, the low fraction of fastigial nucleus neurons whose firing rate and responses to vestibular stimulation were affected by the administration of CuSO4 casts doubt on the notion that nauseogenic visceral inputs modulate motion sickness susceptibility principally through neural pathways that include the cerebellar fastigial nucleus. Instead, it appears that convergence of gastrointestinal and vestibular inputs occurs mainly in the brainstem.

Vestibular nucleus neurons respond to hindlimb movement in the decerebrate cat.

The vestibular nuclei integrate information from vestibular and proprioceptive afferents, which presumably facilitates the maintenance of stable balance and posture. However, little is currently known about the processing of sensory signals from the limbs by vestibular nucleus neurons. This study tested the hypothesis that limb movement is encoded by vestibular nucleus neurons and described the changes in activity of these neurons elicited by limb extension and flexion. In decerebrate cats, we recorded the activity of 70 vestibular nucleus neurons whose activity was modulated by limb movements. Most of these neurons (57/70, 81.4%) encoded information about the direction of hindlimb movement, while the remaining neurons (13/70, 18.6%) encoded the presence of hindlimb movement without signaling the direction of movement. The activity of many vestibular nucleus neurons that responded to limb movement was also modulated by rotating the animal's body in vertical planes, suggesting that the neurons integrated hindlimb and labyrinthine inputs. Neurons whose firing rate increased during ipsilateral ear-down roll rotations tended to be excited by hindlimb flexion, whereas neurons whose firing rate increased during contralateral ear-down tilts were excited by hindlimb extension. These observations suggest that there is a purposeful mapping of hindlimb inputs onto vestibular nucleus neurons, such that integration of hindlimb and labyrinthine inputs to the neurons is functionally relevant.

Excited-State Structure Modifications Due to Molecular Substituents and Exciton Scattering in Conjugated Molecules.

Attachment of chemical substituents (such as polar moieties) constitutes an efficient and convenient way to modify physical and chemical properties of conjugated polymers and oligomers. Associated modifications in the molecular electronic states can be comprehensively described by examining scattering of excitons in the polymer's backbone at the scattering center representing the chemical substituent. Here, we implement effective tight-binding models as a tool to examine the analytical properties of the exciton scattering matrices in semi-infinite polymer chains with substitutions. We demonstrate that chemical interactions between the substitution and attached polymer are adequately described by the analytical properties of the scattering matrices. In particular, resonant and bound electronic excitations are expressed via the positions of zeros and poles of the scattering amplitude, analytically continued to complex values of exciton quasi-momenta. We exemplify the formulated concepts by analyzing excited states in conjugated phenylacetylenes substituted by perylene.

Effects of visceral inputs on the processing of labyrinthine signals by the inferior and caudal medial vestibular nuclei: ramifications for the production of motion sickness.

Neurons located in the caudal aspect of the vestibular nucleus complex have been shown to receive visceral inputs and project to brainstem regions that participate in generating emesis, such as nucleus tractus solitarius and the "vomiting region" in the lateral tegmental field (LTF). Consequently, it has been hypothesized that neurons in the caudal vestibular nuclei participate in triggering motion sickness and that visceral inputs to the vestibular nucleus complex can affect motion sickness susceptibility. To obtain supporting evidence for this hypothesis, we determined the effects of intragastric infusion of copper sulfate (CuSO4) on responses of neurons in the inferior and caudal medial vestibular nuclei to rotations in vertical planes. CuSO4 readily elicits nausea and emesis by activating gastrointestinal (GI) afferents. Infusion of CuSO4 produced a >30 % change in spontaneous firing rate of approximately one-third of neurons in the caudal aspect of the vestibular nucleus complex. These changes in firing rate developed over several minutes, presumably in tandem with the emetic response. The gains of responses to vertical vestibular stimulation of a larger fraction (approximately two-thirds) of caudal vestibular nucleus neurons were altered over 30 % by administration of CuSO4. The response gains of some units went up, and others went down, and there was no significant relationship with concurrent spontaneous firing rate change. These findings support the notion that the effects of visceral inputs on motion sickness susceptibility are mediated in part through the caudal vestibular nuclei. However, our previous studies showed that infusion of CuSO4 produced larger changes in response to vestibular stimulation of LTF neurons, as well as parabrachial nucleus neurons that are believed to participate in generating nausea. Thus, integrative effects of GI inputs on the processing of labyrinthine inputs must occur at brain sites that participate in eliciting motion sickness in addition to the caudal vestibular nuclei. It seems likely that the occurrence of motion sickness requires converging inputs to brain areas that generate nausea and vomiting from a variety of regions that process vestibular signals.

Processing of vestibular inputs by the medullary lateral tegmental field of conscious cats: implications for generation of motion sickness.

The dorsolateral reticular formation of the caudal medulla, the lateral tegmental field (LTF), participates in generating vomiting. LTF neurons exhibited complex responses to vestibular stimulation in decerebrate cats, indicating that they received converging inputs from a variety of labyrinthine receptors. Such a convergence pattern of vestibular inputs is appropriate for a brain region that participates in generating motion sickness. Since responses of brainstem neurons to vestibular stimulation can differ between decerebrate and conscious animals, the current study examined the effects of whole-body rotations in vertical planes on the activity of LTF neurons in conscious felines. Wobble stimuli, fixed-amplitude tilts, the direction of which moves around the animal at a constant speed, were used to determine the response vector orientation, and also to ascertain whether neurons had spatial-temporal convergence (STC) behavior (which is due to the convergence of vestibular inputs with different spatial and temporal properties). The proportion of LTF neurons with STC behavior in conscious animals (25 %) was similar to that in decerebrate cats. Far fewer neurons in other regions of the feline brainstem had STC behavior, confirming findings that many LTF neurons receive converging inputs from a variety of labyrinthine receptors. However, responses to vertical plane vestibular stimulation were considerably different in decerebrate and conscious felines for LTF neurons lacking STC behavior. In decerebrate cats, most LTF neurons had graviceptive responses to rotations, similar to those of otolith organ afferents. However, in conscious animals, the response properties were similar to those of semicircular canal afferents. These differences show that higher centers of the brain that are removed during decerebration regulate the labyrinthine inputs relayed to the LTF, either by gating connections in the brainstem or by conveying vestibular inputs directly to the region.

Responses of neurons in the caudal medullary lateral tegmental field to visceral inputs and vestibular stimulation in vertical planes.

The dorsolateral reticular formation of the caudal medulla, or the lateral tegmental field (LTF), has been classified as the brain's "vomiting center", as well as an important region in regulating sympathetic outflow. We examined the responses of LTF neurons in cats to rotations of the body that activate vestibular receptors, as well as to stimulation of baroreceptors (through mechanical stretch of the carotid sinus) and gastrointestinal receptors (through the intragastric administration of the emetic compound copper sulfate). Approximately half of the LTF neurons exhibited graviceptive responses to vestibular stimulation, similar to primary afferents innervating otolith organs. The other half of the neurons had complex responses, including spatiotemporal convergence behavior, suggesting that they received convergent inputs from a variety of vestibular receptors. Neurons that received gastrointestinal and baroreceptor inputs had similar complex responses to vestibular stimulation; such responses are expected for neurons that contribute to the generation of motion sickness. LTF units with convergent baroreceptor and vestibular inputs may participate in producing the cardiovascular system components of motion sickness, such as the changes in skin blood flow that result in pallor. The administration of copper sulfate often modulated the gain of responses of LTF neurons to vestibular stimulation, particularly for units whose spontaneous firing rate was altered by infusion of drug (median of 459%). The present results raise the prospect that emetic signals from the gastrointestinal tract modify the processing of vestibular inputs by LTF neurons, thereby affecting the probability that vomiting will occur as a consequence of motion sickness.