Comparison of the Impact of a 6 French GlideSheath Slender® and a Conventional Sheath on Distal Radial Artery Occlusion: A Randomized Controlled Trial.

BACKGROUND: There is a lack of randomized clinical trials investigating whether the 6-Fr Glidesheath Slender (GSS) is superior to the 6-Fr conventional radial sheath (CS) with respect to the early-term incidence of distal radial artery occlusion (dRAO) in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) via distal transradial access (dTRA). METHODS: This was a prospective, single-centre trial of patients who were randomized to undergo CAG and/or PCI with either a 6-Fr GSS or a 6-Fr CS. The primary endpoint was the incidence of dRAO at 24 h postoperatively, as evaluated by Doppler ultrasound. RESULTS: A total of 620 patients were included in the study. The baseline patient and procedural characteristics were similar between the two groups. For the primary endpoint, the incidence of dRAO at 24 h after the procedure was 1.0% (3/314) in the GSS group and 3.6% (11/306) in the CS group (RR= 0.266, 95% CI= 0.075-0.943, P= 0.027) according to the intention-to-treat (ITT) analysis. For the secondary endpoints, the incidence of proximal RAO was 0.3% (1/314) in the GSS group and 2.3% (7/306) in the CS group (P= 0.029). Other secondary endpoints, including the puncture success rate, procedural outcomes, other puncture-related outcomes and access-related complications, were not significantly different between the two groups. CONCLUSION: The use of a thin-walled and hydrophilic coating sheath can reduce the incidence of early-term dRAO in patients who undergo CAG and/or PCI via the dTRA.

Comparison of long-term prognoses of percutaneous coronary intervention via distal transradial and conventional transradial access for acute coronary syndrome.

BACKGROUND: Distal transradial access (dTRA) has recently emerged as a new vascular access alternative for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). However, published data on long-term mortality and major adverse cardiac events after PCI via dTRA are inconclusive. The aim of this study was to compare the long-term prognoses of PCI via dTRA and conventional transradial access (cTRA) for acute coronary syndrome (ACS) after 1-3 years of follow-up. METHODS: Patients who were diagnosed with ACS and underwent PCI between January 1, 2020 and December 31, 2021, were retrospectively enrolled. The patients were divided into two groups at a 1:1 ratio, subjected to propensity score matching (PSM), and then followed for 1-3 years after PCI. Cox proportional hazards regression was used to evaluate the relationship between the two access sites and clinical outcomes. RESULTS: Among the 550 patients in the dTRA and cTRA groups, 11 (4.0%) and 19 (6.9%) died during the observation period, respectively. dTRA and cTRA had similar risks of all-cause mortality [hazard ratio (HR) = 0.688; 95% CI = 0.323-1.463; P = 0.331] and major adverse cardiac events (MACEs, HR = 0.806, 95% CI = 0.515-1.263; P = 0.347) after PCI. The risk of cardiovascular mortality (HR = 0.330, 95% CI = 0.107-1.105; P = 0.053), TLR-MACEs (HR = 0.587, 95% CI = 0.339-1.109; P = 0.058), and unplanned revascularization (HR = 0.860, 95% CI = 0.483-1.529; P = 0.606) were not significantly different between the two groups. CONCLUSIONS: PCI via dTRA has the same long-term prognoses as PCI via cTRA in ACS patients, and the compression time and bleeding rate are lower than those in patients undergoing PCI via cTRA.

Comparison of long-term radial artery occlusion via distal vs. conventional transradial access (CONDITION): a randomized controlled trial.

BACKGROUND: The distal transradial access (dTRA) has become an attractive and alternative access to the conventional transradial access (TRA) for cardiovascular interventional diagnosis and/or treatment. There was a lack of randomized clinical trials to evaluate the effect of the dTRA on the long-term radial artery occlusion (RAO). METHODS: This was a prospective, randomized controlled study. The primary endpoint was the incidence of long-term RAO at 3 months after discharge. The secondary endpoints included the successful puncture rate, puncture time, and other access-related complications. RESULTS: The incidence of long-term RAO was 0.8% (3/361) for dTRA and 3.3% (12/365) for TRA (risk ratio = 0.25, 95% confidence interval = 0.07-0.88, P = 0.02). The incidence of RAO at 24 h was significantly lower in the dTRA group than in the TRA group (2.5% vs. 6.7%, P < 0.01). The puncture success rate (96.0% vs. 98.5%, P = 0.03) and single puncture attempt (70.9% vs. 83.9%, P < 0.01) were significantly lower in the dTRA group than in the TRA group. However, the number of puncture attempts and puncture time were higher in the dTRA group. The dTRA group had a lower incidence of bleeding than the TRA group (1.5% vs. 6.0%, P < 0.01). There was no difference in the success rate of the procedure, total fluoroscopy time, or incidence of other access-related complications between the two groups. In the per-protocol analysis, the incidence of mEASY type ≥ II haematoma was significantly lower in the dTRA group, which was consistent with that in the as-treated analysis. CONCLUSIONS: The dTRA significantly reduced the incidence of long-term RAO, bleeding or haematoma. TRIAL REGISTRATION: ClinicalTrials.gov identifer: NCT05253820.

Visualized X-ray Dosimetry for Multienvironment Applications.

X-ray dose detection plays a critical role in various scientific fields, including chemistry, materials, and medicine. However, the current materials used for this purpose face challenges in both immediate and delayed radiation detections. Here, we present a visual X-ray dosimetry method for multienvironment applications, utilizing NaLuF4 nanocrystals (NCs) that undergo a color change from green to red upon X-ray irradiation. By adjustment of the concentrations of Ho3+, the emission color of the NCs can be tuned thanks to the cross-relaxation effects. Furthermore, X-ray irradiation induces generation of trapping centers in NaLuF4:Ho3+ NCs, endowing the generation of mechanoluminescence (ML) behavior upon mechanical stimulation after X-ray irradiation ceases. The ML intensity shows a linear correlation with the X-ray dose, facilitating the detection of delayed radiation. This breakthrough facilitates X-ray dose inspection in flaw detection, nuclear medicine, customs, and civil protection, thereby enhancing opportunities for radiation monitoring and control.

Comparison of the feasibility and safety between distal transradial access and conventional transradial access in patients with acute chest pain: a single-center cohort study using propensity score matching.

BACKGROUND: Distal transradial access (dTRA) has been suggested to have great advantages over cTRA. However, there is a lack of preliminary data on dTRA in patients undergoing emergency coronary angiography (CAG) or percutaneous coronary intervention (PCI). To explore the feasibility and safety of distal transradial access in patients with acute chest pain. METHODS: A total of 1269 patients complaining of acute chest pain in our emergency department from January 2020 to February 2022 were retrospectively included. The patients who met the inclusion criteria were divided into the conventional transradial access (cTRA) group (n = 238) and the dTRA group (n = 158). Propensity score matching was used to minimize the baseline differences. RESULTS: The cannulation success rate in the dTRA group was significantly lower than that in the cTRA group (87.41% vs. 94.81%, p < 0.05). No significant differences in the puncture time and total procedure time were noted between the two groups (p > 0.05). Compared with the cTRA group, the hemostasis duration was significantly shorter [4(4, 4) h vs. 10(8, 10) h, p < 0.001) and the incidence of minor bleeding (BARC Type I and II) was significantly lower in the dTRA group than that in the cTRA group (0.85% vs. 5.48%, p = 0.045). Asymptomatic radial artery occlusion was observed in six patients (5.83%) in the cTRA group and one patient (1.14%) in the dTRA group (p = 0.126). The subgroup analysis of ST-elevation myocardial infarction (STEMI) showed no significant differences in the puncture time, D-to-B time or total procedure time between the two groups. CONCLUSIONS: The dTRA for emergency CAG or PCI has an acceptable success rate and puncture time, a shorter hemostasis time, and a downward trend in RAO rate compared to the cTRA. The dTRA did not increase the D-to-B time in emergency coronary interventions in STEMI patients. On the contrary, a low incidence of RAO by the dTRA created an opportunity for future coronary interventions in non-culprit vessels in the same access. TRIAL REGISTRATION: Retrospectively registered in Chinese Clinical Trial Registry (registry number: ChiCTR2200061104, date of registration: June 15, 2022).

Rationale and design of the optimal antithrombotic treatment for acute coronary syndrome patients with concomitant atrial fibrillation and implanted with new-generation drug-eluting stent: OPtimal management of anTIthroMbotic Agents (OPTIMA)-4 trial.

BACKGROUND: About 5%-15% of acute coronary syndrome (ACS) patients undergoing stent implantation have concomitant atrial fibrillation and need both antiplatelet and anticoagulant therapies. The optimal antithrombotic regimen remains uncertain in this scenario. HYPOTHESIS: A multicenter randomized controlled trial (OPtimal management of anTIthroMbotic Agents [OPTIMA]-4) is designed to test the hypothesis that, for ACS patients with concomitant nonvalvular atrial fibrillation (NVAF) and having low-to-moderate risk of bleeding, clopidogrel is comparable in efficacy but superior in safety compared to ticagrelor while being used in combination with dabigatran after new-generation drug-eluting stent (DES) implantation. METHODS: ACS patients who have low-to-moderate risk of bleeding (e.g., HAS-BLED score ≤ 2) and require anticoagulation therapy (CHA2 DS2 -VASc score ≥ 2) will be recruited after implantation of new-generation DES. A total of 1472 eligible patients will be randomly assigned to receive a 12-month dual antithrombotic treatment of either clopidogrel 75 mg daily or ticagrelor 90 mg twice daily in combination with dabigatran 110 mg twice daily. Participants will be followed up for 12 months after randomization. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, unplanned revascularization, ischemic stroke, and systemic thromboembolism. The primary safety endpoint is set as major bleeding or clinically relevant nonmajor bleeding defined by the International Society of Thrombosis and Hemostasis. The enrollment and follow-up have been launched. RESULTS: The first enrollment occurred on March 12, 2018. The recruitment is anticipated to be completed before December 31, 2024. CONCLUSIONS: The OPTIMA-4 trial offers an opportunity to assess the optimal dual antithrombotic regimen in ACS patients with concomitant NVAF after the implantation of new-generation DES.

Prognostic significance of carbohydrate antigen 125 in stage D heart failure.

BACKGROUND: The predictive value of carbohydrate antigen 125 (CA125) has not been examined in stage D heart failure (HF) patients, regardless of left ventricular ejection fraction (LVEF). We sought to quantify the prognostic usefulness in predicting death and HF readmission in this cohort. METHODS: According to CA125 levels above and below the median (65.7 U/ml), 176 stage D HF patients including more than half (50.6%) had LVEF > 40% were divided into 2 groups. RESULTS: A total of 106 (60.2%) deaths and 102 deaths due to the cardiovascular disease were identified. All-cause death/HF readmission and MACE occurred in 157 patients (89.2%) during 18 months (16-20) of follow-up. By the Kaplan-Meier method, subjects with CA125 ≥ 65.7 U/ml exhibited higher 1-year mortality rate (59.3% vs. 31.0%, P < 0.001) and 1-year death/HF rehospitalization rate (94.2% vs. 80.6%, P < 0.001). In univariate Cox analysis, CA125 (categorized) was a significant prognostic factor for all-cause death, cardiovascular mortality, death/HF readmission and MACE. Based on multivariate Cox analysis, elevated CA125 was still significant for all-cause death, cardiovascular mortality, death/HF readmission and MACE. CONCLUSIONS: In stage D HF patients, elevated CA125 levels were highly predictive of all-cause death, cardiovascular mortality, all-cause death/HF readmission and MACE, which can be used for better risk stratification.

Interaction between triglyceride-glucose index and thyroid hormones on coronary artery disease risk in patient with euthyroid.

Background: Triglyceride-glucose (TyG) index is an effective indicator in indentifying in pre-diabetes, diabetes, and coronary artery disease (CAD). However, the value of TyG index combined with thyroid hormones (THs) to affect CAD has not been fully evaluated. Here, we investigated the association between TyG index and THs and further studied the impacts of TyG index and THs on CAD in euthyroid. Methods: Subjects (1,297) with euthyroid who underwent selective coronary angiography (CAG) were enrolled in the present study, including 893 patients with CAD and 404 controls. The association between TyG index and THs were analyzed by linear regression models. Multivariate logistic regression analysis was used to evaluate the interaction of TyG and THs with the risk of CAD. According to the cutoff value of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and TyG index, the patients were respectively separated into four groups: low TyG/FT3 (low or high), high TyG/FT3 (low or high), low TyG/FT4 (low or high), high TyG/FT4 (low or high), low TyG/TSH (low or high), high TyG/TSH (low or high). Results: The baseline analysis showed that FT4 level differs among the three groups according to the tertile of the TyG index. Multiple linear regression analysis revealed decreased serum FT3 level and serum FT4 level as an independent risk factor for elevated TyG index. After adjusting for confounding variables, multiple logistic regression analysis showed that patients with lower TyG index and higher FT3 level had an important protective effect on CAD when considering patients with lower TyG index and FT3 level as reference(OR = 0.536, 95% CI: 0.369-0.778, P = 0.001). Patients with higher TyG index and FT4 level (lower or higher) had a significantly increased risk of CAD (OR 1.656, 95% CI: 1.117-2.455; OR = 1.920, 95% CI: 1.279-2.848, respectively). The area under the curve for the combined diagnosis of CAD by TyG index and FT3 level is 0.615. Conclusions: These findings suggest that TyG is independently negatively correlated with FT3 or FT4 in euthyroid. In addition, there was a significant interaction between TyG index and THs on the risk of CAD.

Analysis and modeling of myopia-related factors based on questionnaire survey.

With the rapid development of science and technology, the trend of low age myopia is becoming increasingly significant. The latest national survey done by the Chinese government found that more than 80% of Chinese teenagers suffer from myopia. Adolescent myopia is closely related to living environment, heredity, and living habits. Quantifying the relationship between myopia and living environment, heredity, and living habits is conductive to the prevention and intervention of adolescent myopia. In this study, we investigated the relationships between four main factors (environment, habits, parental vision, and demographic) and myopia status by analyzing the questionnaire data. Data were collected from Chengdu, China in 2021, including 2808 myopia samples and 5693 non-myopia samples, with a total of 22 features. Then, these 22 features were inputted into three machine learning algorithms to discriminate the two classes of samples. Results show that the computational model could produce an AUC of 0.768. To pick out the most important features which play important roles in classification, we used incremental feature selection strategy to screen the 22 features. As a result, we found that the 4 most influential features with XGBoost could achieve a competitive AUC of 0.764. To further investigate the risk and protective factors affecting adolescent myopia, we used OR values derived from MLE-LR to analyze the relationship between 22 features and adolescent myopia. Results showed that the age variable was the most significant risk factor for myopia, followed by the myopia status of parents. The most protective factor for eyesight is the measure taken by the children, followed by the distance between books and eyes when reading. These discoveries can guide the prevention and control of myopia in children and adolescents.

Efficacy and Safety of Coronary Intervention via Distal Transradial Access (dTRA) in Patients with Low Body Mass Index.

The study aimed to investigate the efficacy and safety of coronary intervention via distal transradial access (dTRA) in patients with low body mass index (BMI). A total of 67 patients with low BMI who underwent coronary intervention, comprising 29 patients via dTRA and 38 patients via conventional transradial access (cTRA), were retrospectively included. There was no significant difference in the puncture success rate between the two groups (dTRA 96.6%, cTRA 97.4%, P=0.846). Compared with the cTRA group, the success rate of one-needle puncture in the dTRA group was lower (51.7% vs. 81.6%, P=0.020). The compression haemostasis time in the dTRA group was shorter than that in the cTRA group (P < 0.001). However, the incidence of radial artery occlusion was lower in the dTRA group than in the cTRA group (4.0% vs. 33.3%, P=0.007). In conclusion, coronary intervention via dTRA was safe and effective in patients with low BMI.

Safety and efficacy of coronary angiography and percutaneous coronary intervention via distal transradial artery access in the anatomical snuffbox: a single-centre prospective cohort study using a propensity score method.

BACKGROUND: This study investigated the safety and efficacy of coronary angiography (CAG) and percutaneous coronary intervention (PCI) via distal transradial artery access (d-TRA). METHODS: For this single-centre prospective cohort study, a total of 1066 patients who underwent CAG or PCI procedures from September 2019 to November 2020 were included. Patients were divided into two groups: the d-TRA group (346) and the conventional transradial artery access (c-TRA) group (720) based on access site. A total of 342 pairs of patients were successfully matched using propensity score matching (PSM) for subsequent analysis. RESULTS: No significant differences in puncture success rate, procedural method, procedural time, sheath size, contrast dosage or fluoroscopy time were noted between the two groups. The puncture time in the d-TRA group was longer than that in the c-TRA group (P < 0.01), and the procedure success rate was lower than that in the c-TRA group (90.94% vs. 96.49%, P = 0.01). The haemostasis time in the d-TRA group was shorter than that in the c-TRA group (P < 0.01), and the visual analogue scale (VAS) was lower than that in the c-TRA group (P < 0.01). In addition, the prevalence of bleeding and haematoma in the d-TRA group was lower than that in the c-TRA group (1.75% vs. 7.31%, P < 0.01; 0.58% vs. 3.22%, P = 0.01, respectively). No significant difference in the incidence of numbness was noted between the two groups. No other complications were found in two groups. CONCLUSION: d-TRA is as safe and effective as c-TRA for CAG and PCI. It has the advantages of improved comfort and fewer complications. Trail registration Chinese Clinical Trial Registry, ChiCTR1900026519.

The ratio of HDL-C to apoA-I interacts with free triiodothyronine to modulate coronary artery disease risk.

OBJECTIVE: In the present work, research was carried out to explore the correlation between the high-density lipoprotein cholesterol (HDL-C)/apolipoprotein A-I (apoA-I) ratio and serum free triiodothyronine (FT3) and their interaction on the risk of coronary artery disease (CAD). METHODS: A total of 1686 patients who underwent selective coronary angiography were enrolled in the present study, including 1279 patients with CAD and 407 controls. The subjects were divided into three groups according to tertiles of the HDL-C/apoA-I ratio. Binary logistic regression analysis was used to evaluate the interaction of the HDL-C/apoA-I ratio and FT3 level with the risk of CAD. RESULTS: The group with the highest HDL-C/apoA-I ratio had the lowest levels of FT3. Multiple linear regression analysis showed that the HDL-C/apoA-I ratio was negatively associated with FT3 after adjusting for age, sex, body mass index (BMI), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), FT4 and TSH. A logistic regression model showed that a high HDL-C/apoA-I ratio (> 0.89 mmol/g) and high FT3 levels (> 4.5 pmol/l) were protective factors for CAD. Patients with a lower HDL-C/apoA-I ratio (≤ 0.89 mmol/g) and lower FT3 level (≤ 4.5 pmol/l) had an increased risk of CAD (OR = 2.441, P = 0.000, S = 1.13, AP = 0.068, AP* = 0.116, RERI = 0.168). CONCLUSIONS: The HDL-C/apoA-I ratio was negatively associated with FT3, and there was a significant interaction between the HDL-C/apoA-I ratio and FT3 with the risk of CAD.

Optimizing 3D Convolution Kernels on Stereo Matching for Resource Efficient Computations.

Despite recent stereo matching algorithms achieving significant results on public benchmarks, the problem of requiring heavy computation remains unsolved. Most works focus on designing an architecture to reduce the computational complexity, while we take aim at optimizing 3D convolution kernels on the Pyramid Stereo Matching Network (PSMNet) for solving the problem. In this paper, we design a series of comparative experiments exploring the performance of well-known convolution kernels on PSMNet. Our model saves the computational complexity from 256.66 G MAdd (Multiply-Add operations) to 69.03 G MAdd (198.47 G MAdd to 10.84 G MAdd for only considering 3D convolutional neural networks) without losing accuracy. On Scene Flow and KITTI 2015 datasets, our model achieves results comparable to the state-of-the-art with a low computational cost.

Atherogenic index of plasma is related to coronary atherosclerotic disease in elderly individuals: a cross-sectional study.

BACKGROUND: Dyslipidaemia plays an important role in coronary atherosclerotic disease (CAD). The relationship between the atherogenic index of plasma (AIP) and CAD in elderly individuals was explored in this study. METHODS: Elderly individuals (age ≥ 65 years) who underwent coronary angiography from January 2016 to October 2020 were consecutively enrolled in the study. RESULTS: A total of 1313 individuals, including 354 controls (non-CAD) and 959 CAD patients, were enrolled. In univariate analysis of all populations, the adjusted AIP (aAIP) in the CAD group was 1.13 (0.96, 1.3), which was significantly higher than that in the controls [1.07 (0.89, 1.26)]. However, in subgroup analyses, this phenomenon was only present in males. In addition, further study showed that aAIP was positively related to CAD severity. In binary logistic regression analyses, after adjusting for sex, age, smoking status, primary hypertension (PH), type 2 diabetes mellitus (T2DM), heart rate (HR), white blood cell (WBC) and platelet (PLT), AIP remained independently related to CAD in elderly individuals and was superior to traditional and other nontraditional lipid indices. Subgroup analyses showed that AIP independently influenced CAD risk in males. Ultimately, sensitivity analyses were performed excluding all coronary emergencies, and the final results were similar. CONCLUSIONS: AIP was positively related to the risk and severity of CAD in elderly individuals and was superior to traditional and other nontraditional lipid profiles. However, this association only exists in elderly males.

Recanalization of the occluded radial artery via distal transradial access in the anatomic snuffbox.

BACKGROUND: Radial artery occlusion is a common complication after coronary angiography and percutaneous coronary intervention via the transradial access. In recent years, coronary angiography and percutaneous coronary intervention via the distal transradial access has gradually emerged, but recanalization of the occluded radial artery through the distal transradial access has rarely been reported. CASE PRESENTATION: A 67-year-old female with arterial hypertension and diabetes mellitus was admitted to the hospital due to chest pain for three hours. She was diagnosed with acute myocardial infarction. After admission, the patient successfully underwent emergency coronary angiography and percutaneous coronary intervention through the right transradial access. Radial artery occlusion was found after the operation, and recanalization was successfully performed through the right distal transradial access before discharge. Immediately after the operation and one month later, vascular ultrasonography showed that the antegrade flow was normal. CONCLUSIONS: This report presents a case of radial artery occlusion after emergency coronary angiography and percutaneous coronary intervention in which recanalization was successfully performed through the right distal transradial access. This case demonstrates that recanalization of a radial artery occlusion via the distal transradial access is safe and feasible.

Heterogeneity of Purkinje cell simple spike-complex spike interactions: zebrin- and non-zebrin-related variations.

KEY POINTS: Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spikes. Although they are generated by distinct mechanisms, interactions between the two spike types exist. Zebrin staining produces alternating positive and negative stripes of PCs across most of the cerebellar cortex. Thus, here we compared simple spike-complex spike interactions both within and across zebrin populations. Simple spike activity undergoes a complex modulation preceding and following a complex spike. The amplitudes of the pre- and post-complex spike modulation phases were correlated across PCs. On average, the modulation was larger for PCs in zebrin positive regions. Correlations between aspects of the complex spike waveform and simple spike activity were found, some of which varied between zebrin positive and negative PCs. The implications of the results are discussed with regard to hypotheses that complex spikes are triggered by rises in simple spike activity for either motor learning or homeostatic functions. ABSTRACT: Purkinje cells (PCs) generate two types of action potentials, called simple and complex spikes (SSs and CSs). We first investigated the CS-associated modulation of SS activity and its relationship to the zebrin status of the PC. The modulation pattern consisted of a pre-CS rise in SS activity, and then, following the CS, a pause, a rebound, and finally a late inhibition of SS activity for both zebrin positive (Z+) and negative (Z-) cells, though the amplitudes of the phases were larger in Z+ cells. Moreover, the amplitudes of the pre-CS rise with the late inhibitory phase of the modulation were correlated across PCs. In contrast, correlations between modulation phases across CSs of individual PCs were generally weak. Next, the relationship between CS spikelets and SS activity was investigated. The number of spikelets/CS correlated with the average SS firing rate only for Z+ cells. In contrast, correlations across CSs between spikelet numbers and the amplitudes of the SS modulation phases were generally weak. Division of spikelets into likely axonally propagated and non-propagated groups (based on their interspikelet interval) showed that the correlation of spikelet number with SS firing rate primarily reflected a relationship with non-propagated spikelets. In sum, the results show both zebrin-related and non-zebrin-related physiological heterogeneity in SS-CS interactions among PCs, which suggests that the cerebellar cortex is more functionally diverse than is assumed by standard theories of cerebellar function.

The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper.

For many decades, the predominant view in the cerebellar field has been that the olivocerebellar system's primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here, we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum and might also play a role in development. We then consider the potential problems and benefits of it having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, and variable complex spike waveforms) make it more or less suitable for one or the other of these functions, and why having multiple functions makes sense from an evolutionary perspective. We did not attempt to reach a consensus on the specific role(s) the olivocerebellar system plays in different types of movements, as that will ultimately be determined experimentally; however, collectively, the various contributions highlight the flexibility of the olivocerebellar system, and thereby suggest that it has the potential to act in both the motor learning and motor control functions of the cerebellum.

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes.

KEY POINTS: Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. ABSTRACT: Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning.

Modulation of Purkinje cell complex spike waveform by synchrony levels in the olivocerebellar system.

Purkinje cells (PCs) generate complex spikes (CSs) when activated by the olivocerebellar system. Unlike most spikes, the CS waveform is highly variable, with the number, amplitude, and timing of the spikelets that comprise it varying with each occurrence. This variability suggests that CS waveform could be an important control parameter of olivocerebellar activity. The origin of this variation is not well known. Thus, we obtained extracellular recordings of CSs to investigate the possibility that the electrical coupling state of the inferior olive (IO) affects the CS waveform. Using multielectrode recordings from arrays of PCs we showed that the variance in the recording signal during the period when the spikelets occur is correlated with CS synchrony levels in local groups of PCs. The correlation was demonstrated under both ketamine and urethane, indicating that it is robust. Moreover, climbing fiber reflex evoked CSs showed an analogous positive correlation between spikelet-related variance and the number of cells that responded to a stimulus. Intra-IO injections of GABA-A receptor antagonists or the gap junction blocker carbenoxolone produced correlated changes in the variance and synchrony levels, indicating the presence of a causal relationship. Control experiments showed that changes in variance with synchrony were primarily due to changes in the CS waveform, as opposed to changes in the strength of field potentials from surrounding cells. Direct counts of spikelets showed that their number increased with synchronization of CS activity. In sum, these results provide evidence of a causal link between two of the distinguishing characteristics of the olivocerebellar system, its ability to generate synchronous activity and the waveform of the CS.

Systematic regional variations in Purkinje cell spiking patterns.

In contrast to the uniform anatomy of the cerebellar cortex, molecular and physiological studies indicate that significant differences exist between cortical regions, suggesting that the spiking activity of Purkinje cells (PCs) in different regions could also show distinct characteristics. To investigate this possibility we obtained extracellular recordings from PCs in different zebrin bands in crus IIa and vermis lobules VIII and IX in anesthetized rats in order to compare PC firing characteristics between zebrin positive (Z+) and negative (Z-) bands. In addition, we analyzed recordings from PCs in the A2 and C1 zones of several lobules in the posterior lobe, which largely contain Z+ and Z- PCs, respectively. In both datasets significant differences in simple spike (SS) activity were observed between cortical regions. Specifically, Z- and C1 PCs had higher SS firing rates than Z+ and A2 PCs, respectively. The irregularity of SS firing (as assessed by measures of interspike interval distribution) was greater in Z+ bands in both absolute and relative terms. The results regarding systematic variations in complex spike (CS) activity were less consistent, suggesting that while real differences can exist, they may be sensitive to other factors than the cortical location of the PC. However, differences in the interactions between SSs and CSs, including the post-CS pause in SSs and post-pause modulation of SSs, were also consistently observed between bands. Similar, though less strong trends were observed in the zonal recordings. These systematic variations in spontaneous firing characteristics of PCs between zebrin bands in vivo, raises the possibility that fundamental differences in information encoding exist between cerebellar cortical regions.