Human estimates of descending objects' motion are more accurate than those of ascending objects regardless of gravity information.

Humans can accurately estimate and track object motion, even if it accelerates. Research shows that humans exhibit superior estimation and tracking performance for descending (falling) than ascending (rising) objects. Previous studies presented ascending and descending targets along the gravitational and body axes in an upright posture. Thus, it is unclear whether humans rely on congruent information between the direction of the target motion and gravity or the direction of the target motion and longitudinal body axes. Two experiments were conducted to explore these possibilities. In Experiment 1, participants estimated the arrival time at a goal for both upward and downward motion of targets along the longitudinal body axis in the upright (both axes of target motion and gravity congruent) and supine (both axes incongruent) postures. In Experiment 2, smooth pursuit eye movements were assessed while tracking both targets in the same postures. Arrival time estimation and smooth pursuit eye movement performance were consistently more accurate for downward target motion than for upward motion, irrespective of posture. These findings suggest that the visual experience of seeing an object moving along an observer's leg side in everyday life may influence the ability to accurately estimate and track the descending object's motion.

Lenvatinib Mitigates Transarterial Embolization-Induced Polarization of Tumor-Associated Macrophages in a Rat Hepatocellular Carcinoma Model.

PURPOSE: To investigate the effect of transarterial embolization (TAE) on macrophage polarization and the modulatory effect of lenvatinib when used in combination with TAE in a rat hepatocellular carcinoma model. MATERIALS AND METHODS: A N1S1-bearing orthotopic rat model was subjected to TAE and administered 5 mg/kg of lenvatinib. CD8+, CD68+, and CD206+ cells were examined in 4 groups: sham (n = 5), lenvatinib (n = 5), TAE (n = 5), and combination of TAE and lenvatinib (n = 5). Transcriptome analysis was performed to assess gene expression related to macrophage polarization in the sham, TAE, and combination groups. An in vitro coculture experiment with bone marrow-derived macrophages was performed to identify lenvatinib target in macrophage polarization. RESULTS: There were no significant differences in the number of CD8+ and CD68+ cells among the 4 groups. Tumor-associated macrophage positivity for CD206 was significantly higher in the TAE group (58.1 ± 20.9) than in the sham (11.2 ± 14.3; P < .001) and combination (27.1 ± 19.7; P = .003) groups. In the transcriptome analysis, compared with the genes in the sham group, 5 macrophage polarization-related genes, including St6gal1, were upregulated by more than 1.5 fold in the TAE group and downregulated by more than 1.5 fold in the combination group. The coculture experiment showed that lenvatinib did not affect macrophages but affected N1S1 cells, leading to macrophage polarization. CONCLUSIONS: TAE-induced M2 macrophage polarization. Lenvatinib administration with TAE could reprogram macrophage polarization, improving tumor immune microenvironment.

Emerging order of anomalous eye movements with progressive drowsiness.

It has been widely recognized that human alertness is reflected in the eyes (e.g., when drowsiness, miosis, slow saccades, divergence, less compensatory vestibulo-ocular reflex, and less-accurate optokinetic response and smooth pursuit emerge). Previous studies that discovered these pupil/oculomotor anomalous behaviors along with lowering alertness evaluated only one or a few of them simultaneously, thus their emergence order is yet unknown. Presently, we focused on the following five pupil/oculomotor behaviors that can be evaluated under a natural stationary environment without giving external sensory stimulations: saccades, slow-phase eye movements, vergence, pupil diameter, and blinks. We demonstrate that their anomalous behaviors emerge in the following order: first: frequent saccades; second: slow saccades; third: divergence & miosis, then slow eye movement, while elongated eyelid closure duration emerges randomly in this sequence. These results provide a basis for the oculo-pupillometry-enabling objective monitoring of progressive drowsiness.

Hepatic Artery Embolization Enhances Expression of Programmed Cell Death 1 Ligand 1 in an Orthotopic Rat Hepatocellular Carcinoma Model: In Vivo and in Vitro Experimentation.

PURPOSE: To evaluate the effects of hepatic artery embolization (HAE) on the expression of programmed cell death 1 ligand 1 (PD-L1) in an orthotopic rat hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: A rat HCC model was established in Sprague-Dawley rats with the RH7777 cell line. Six animals each were assigned to receive HAE or sham treatment. Liver tissues were harvested 24 h after the procedure. Immunohistochemistry (IHC) was used to compare expression of PD-L1 and hypoxia-inducible factor (HIF)-1α in the intratumoral and peritumoral regions and normal liver tissue. In vitro cell culture study was performed for 24 h under normoxic and hypoxic conditions, and protein expression of PD-L1 and HIF-1α and the effects of HIF-1α inhibitors were assessed. RESULTS: IHC showed that PD-L1- and HIF-1α-positive areas were significantly larger in the HAE group vs the sham group in intratumoral (P = .006 and P < .001, respectively) and peritumoral regions (both P < .001). The expression of PD-L1 positively correlated with HIF-1α expression in the intratumoral region (r2 = 0.551; P < .001). In vitro cell culture study revealed that protein expression of PD-L1 and HIF-1α were significantly higher when cells were incubated under hypoxic vs normoxic conditions (P = .028 and P = .010, respectively). PD-L1 expression was suppressed significantly when the HIF-1α inhibitor rapamycin was added to the culture medium (P = .024). CONCLUSIONS: HAE enhances intratumoral and peritumoral PD-L1 expression in a rat HCC model. The HIF-1α pathway is a possible mechanism underlying increased intratumoral PD-L1 expression after HAE.

Vestibulo-ocular reflex characteristics during unidirectional translational whole-body vibration without head restriction.

The vestibulo-ocular reflex (VOR) plays a crucial role in ocular stability. However, VOR characteristics under realistic whole-body vibration conditions, particularly without head restriction, remain unclear. The aim of this study was to characterise the VOR over a wide range of whole-body vibration frequencies (0.7-10 Hz), such as occur when driving a car. Eye and head movements were measured in response to unidirectional translational whole-body vibration that resembled actual vehicle vibrations. The VOR was then modelled by regressing eye velocity data on multiple head movement components. Results showed that the VOR was explained by angular velocity, linear acceleration, and linear jerk components of the head movements. Because the VOR in response to head linear-jerk components disrupted ocular stability in the current experimental setup, our results suggest that degraded vision in whole-body vibratory environments might be partially attributable to jerky head movements. Practitioner summary: The vestibulo-ocular reflex (VOR) during unidirectional translational whole-body vibration without head restriction was modelled using multiple head movement components, with the aim of characterising the VOR. Results showed that the VOR was explained by angular velocity, linear acceleration, and linear jerk components of head movements.

Cerebellar Role in Predictive Control of Eye Velocity Initiation and Termination.

Predictive motor control is essential to achieve rapid and precise motor action in all vertebrates. Visuomotor transformations have been a popular model system to study the underlying neural mechanisms, in particular, the role of the cerebellum in both predictive and gain adaptations. In all species, large-field visual motion produces an involuntary conjugate ocular movement facilitating gaze stabilization called the optokinetic response. Gain adaptation can be induced by prolonged optokinetic visual stimulation; and if the visual stimulation is temporally periodic, predictive behavior emerges. Two predictive timing components were identifiable in this behavior. The first was prediction of stimulus initiation (when to move) and the other was stimulus termination (when to stop). We designed visual training that allowed us to evaluate initiation and termination independently that included the recording of cerebellar activity followed by acute and chronic cerebellar removal in goldfish of both sexes. We found that initiation and termination predictions were present in the cerebellum and more robust than conflicting visual sensory signals. Each prediction could be acquired independently, and both the acquisition and maintenance of each component were cerebellar-dependent. Subsequent analysis of the neuronal connectivity strongly supports the hypothesis that the acquired eye velocity behaviors were dependent on feedforward velocity buildup signals from the brainstem, but the adaptive timing mechanism itself originates within the circuitry of the cerebellum.SIGNIFICANCE STATEMENT Predictive and rapid motor control is essential in our daily life, such as in the playing of musical instruments or sports. The current work evaluates timing of a visuomotor behavior shown to be similar in humans as well as goldfish. Given the latter species' known brainstem cerebellar neuronal connectivity and experimental advantage, it was possible to demonstrate the cerebellum to be necessary for acquisition and maintenance of both the initiation and termination components of when to move and to stop. All evidence in this study points to the adaptive predictive control site to lie within the cerebellar circuitry.

Investigation of the characteristics of headache due to unruptured intracranial vertebral artery dissection.

BACKGROUND AND PURPOSE: It is sometimes difficult to diagnose intracranial vertebral artery dissection in patients with headache as the only symptom. Knowledge of the characteristics of the headache would facilitate the diagnosis. In this study, we aimed to clarify the characteristics of intracranial vertebral artery dissection-related headache using our original self-administered questionnaire. METHODS: Via the questionnaire, we ascertained headache characteristics and investigated whether they differed between two types of unruptured intracranial vertebral artery dissection, headache type and ischemic type, based on analysis of the responses. Then, we tried to validate the consistency of commonly used criteria for intracranial artery dissection by comparing them with our results. RESULTS: Thirty-seven patients were analyzed. Our results identified the following seven headache characteristics in patients with intracranial vertebral artery dissection: (i) occurring in the occipitonuchal region (89%); (ii) unilateral (81%); (iii) pulsatile (70%); (iv) of acute onset (70%); (v) severe (73%); (vi) without nausea or vomiting (73%); and (vii) with concomitant clinical symptoms unrelated to ischemia (81%). Comparison of headache characteristics between the two types of intracranial vertebral artery dissection headache showed that the pain was significantly more severe in headache type than ischemic type intracranial vertebral artery dissection ( p = 0.01). Concomitant clinical symptoms occurred significantly more often in ischemic type than headache type intracranial vertebral artery dissection ( p = 0.03). Our results generally satisfied the established headache diagnostic criteria. CONCLUSION: The pain characteristics of headache type and ischemic type intracranial vertebral artery dissection shown in our study may facilitate its diagnosis.

Medaka and zebrafish contactin1 mutants as a model for understanding neural circuits for motor coordination.

A spontaneous medaka ro mutant shows abnormal wobbling and rolling swimming behaviors. By positional cloning, we mapped the ro locus to a region containing the gene encoding Contactin1b (Cntn1b), which is an immunoglobulin (Ig)-superfamily domain-containing membrane-anchored protein. The ro mutant had a deletion in the cntn1b gene that introduced a premature stop codon. Furthermore, cntn1b mutants generated by the CRISPR/Cas9 system and trans-heterozygotes of the CRISPR mutant allele and ro had abnormal swimming behavior, indicating that the cntn1b gene was responsible for the ro-mutant phenotype. We also established zebrafish cntn1a and cntn1b mutants by transcription activator-like effector nucleases (TALENs). Zebrafish cntn1b but not cntn1a mutants showed abnormal swimming behaviors similar to those in the ro mutant, suggesting that Cntn1b plays a conserved role in the formation or function of the neural circuits that control swimming in teleosts. Although Cntn1-deficient mice have abnormal cerebellar neural circuitry, there was no apparent histological abnormality in the cerebellum of medaka or zebrafish cntn1b mutants. The medaka cntn1b mutants had defective optokinetic response (OKR) adaptation and abnormal rheotaxis (body positioning relative to water flow). Medaka and zebrafish cntn1b mutants are effective models for studying the neural circuits involved in motor learning and motor coordination.

Computational Theory Underlying Acute Vestibulo-ocular Reflex Motor Learning with Cerebellar Long-Term Depression and Long-Term Potentiation.

The vestibulo-ocular reflex (VOR) can be viewed as an adaptive control system that maintains compensatory eye movements during head motion. As the cerebellar flocculus is intimately involved in this adaptive motor control of the VOR, the VOR has been a popular model system for investigating cerebellar motor learning. Long-term depression (LTD) and long-term potentiation (LTP) at the parallel fiber-Purkinje cell synapses are considered to play major roles in cerebellar motor learning. A recent study using mutant mice demonstrated cerebellar motor learning with hampered LTD; the study concluded that the parallel fiber-Purkinje cell LTD is not essential. More recently, multiple forms of plasticity have been found in the cerebellum, and they are believed to contribute to cerebellar motor learning. However, it is still unclear how synaptic plasticity modifies the signal processing that underlies motor learning in the flocculus. A computational simulation suggested that the plasticity present in mossy fiber-granule cell synapses improves VOR-related sensory-motor information transferred into granule cells, whereas the plasticity in the molecular layer stores this information as a memory under guidance from climbing fiber teaching signals. Thus, motor learning and memory are thought to be induced mainly by LTD and LTP at parallel fiber-Purkinje cell synapses and by rebound potentiation at molecular interneuron-Purkinje cell synapses among the multiple forms of plasticity in the cerebellum. In this study, we focused on the LTD and LTP at parallel fiber-Purkinje cell synapses. Based on our simulation, we propose that acute VOR motor learning accomplishes by simultaneous enhancement of eye movement signals via LTP and suppression of vestibular signals via LTD to increase VOR gain (gain-up learning). To decrease VOR gain (gain-down learning), these two signals are modified in the opposite directions; namely, LTD suppresses eye movement signals, whereas LTP enhances vestibular signals.

A knock-in mouse model of N-terminal R420W mutation of cardiac ryanodine receptor exhibits arrhythmogenesis with abnormal calcium dynamics in cardiomyocytes.

Cardiac ryanodine receptor gene (RyR2) mutations cause fatal arrhythmogenic diseases such as catecholaminergic polymorphic ventricular tachycardia and arrhythmogenic right ventricular cardiomyopathy. The N-terminal region of RyR2 is one of the hot spots for mutations. In this study, we investigated cardiac phenotypes of a knock-in mouse model carrying R420W mutation of RyR2. The N-terminal R420W mutation has already been found in juvenile sudden death cadavers of unrelated families. The depolarization-induced Ca(2+) transient amplitude was significantly lower in cardiomyocytes from RyR2(R420W/R420W) mice compared with wild-type mice. The time to peak of the Ca(2+) transient was significantly increased in RyR2(R420W/R420W) mice. Furthermore, the prolonged decay time from the peak of the Ca(2+) transient was detected in RyR2(R420W/R420W) mice. ECG telemetry revealed that various types of arrhythmias were induced in RyR2(R420W/R420W) mice in response to administration of caffeine and adrenaline. The mutant mice showed high occurrences of arrhythmias in response to heart stimulants compared with wild-type mice. These findings suggest that R420W mutation impairs depolarization-induced Ca(2+) oscillation in cardiomyocytes, which possibly results in sudden death due to stress-induced arrhythmias.

Artificial cerebellum on FPGA: realistic real-time cerebellar spiking neural network model capable of real-world adaptive motor control.

The cerebellum plays a central role in motor control and learning. Its neuronal network architecture, firing characteristics of component neurons, and learning rules at their synapses have been well understood in terms of anatomy and physiology. A realistic artificial cerebellum with mimetic network architecture and synaptic plasticity mechanisms may allow us to analyze cerebellar information processing in the real world by applying it to adaptive control of actual machines. Several artificial cerebellums have previously been constructed, but they require high-performance hardware to run in real-time for real-world machine control. Presently, we implemented an artificial cerebellum with the size of 104 spiking neuron models on a field-programmable gate array (FPGA) which is compact, lightweight, portable, and low-power-consumption. In the implementation three novel techniques are employed: (1) 16-bit fixed-point operation and randomized rounding, (2) fully connected spike information transmission, and (3) alternative memory that uses pseudo-random number generators. We demonstrate that the FPGA artificial cerebellum runs in real-time, and its component neuron models behave as those in the corresponding artificial cerebellum configured on a personal computer in Python. We applied the FPGA artificial cerebellum to the adaptive control of a machine in the real world and demonstrated that the artificial cerebellum is capable of adaptively reducing control error after sudden load changes. This is the first implementation and demonstration of a spiking artificial cerebellum on an FPGA applicable to real-world adaptive control. The FPGA artificial cerebellum may provide neuroscientific insights into cerebellar information processing in adaptive motor control and may be applied to various neuro-devices to augment and extend human motor control capabilities.

Learning capabilities to resolve tilt-translation ambiguity in goldfish.

Introduction: Spatial orientation refers to the perception of relative location and self-motion in space. The accurate formation of spatial orientation is essential for animals to survive and interact safely with their environment. The formation of spatial orientation involves the integration of sensory inputs from the vestibular, visual, and proprioceptive systems. Vestibular organs function as specialized head motion sensors, providing information regarding angular velocity and linear acceleration via the semicircular canals and otoliths, respectively. However, because forces arising from the linear acceleration (translation) and inclination relative to the gravitational axis (tilt) are equivalent, they are indistinguishable by accelerometers, including otoliths. This is commonly referred to as the tilt - translation ambiguity, which can occasionally lead to the misinterpretation of translation as a tilt. The major theoretical frameworks addressing this issue have proposed that the interpretation of tilt versus translation may be contingent on an animal's previous experiences of motion. However, empirical confirmation of this hypothesis is lacking. Methods: In this study, we conducted a behavioral experiment using goldfish to investigate how an animal's motion experience influences its interpretation of tilt vs. translation. We examined a reflexive eye movement called the vestibulo-ocular reflex (VOR), which compensatory-rotates the eyes in response to head motion and is known to reflect an animal's three-dimensional head motion estimate. Results: We demonstrated that the VORs of naïve goldfish do not differentiate between translation and tilt at 0.5 Hz. However, following prolonged visual-translation training, which provided appropriate visual stimulation in conjunction with translational head motion, the VORs were capable of distinguishing between the two types of head motion within 3 h. These results were replicated using the Kalman filter model of spatial orientation, which incorporated the variable variance of process noise corresponding to the accumulated motion experience. Discussion: Based on these experimental and computational findings, we discuss the neural mechanism underlying the resolution of tilt-translation ambiguity within a context analogous to, yet distinct from, previous cross-axis VOR adaptations.

The Effect of Japanese Herbal Medicines (Kampo) Goreisan and Saireito on the Prevention of Recurrent Chronic Subdural Hematoma: A Prospective Randomized Study.

BACKGROUND AND OBJECTIVES: Chronic subdural hematoma (CSDH) sometimes recurs after surgical treatment and requires reoperation. In Japan, Japanese herbal medicines (Kampo), such as Goreisan and Saireito, have been used as adjunctive therapies to prevent the recurrence of CSDH. However, no prospective randomized study has proven the efficacy of Kampo medicine in all patients. To investigate whether Goreisan and Saireito reduce the postoperative recurrence of CSDH in a prospective randomized study. METHODS: Between April 2017 and July 2019, a total of 118 patients who underwent initial burr hole surgery for CSDH were randomly assigned to the following 3 groups: (1) Goreisan for 3 months (Group G), (2) Saireito for 3 months (Group S), and (3) no medication (Group N). The primary end point was symptomatic recurrence within 3 months postoperatively, and the secondary end point was complications associated with the administration of Kampo medicine. RESULTS: Among 118 patients, 114 (Group N, n = 39; Group G, n = 37; and Group S, n = 38) were included in our analysis. In this study, byakujutsu (containing Atractylodes rhizome ) Goreisan and Saireito were used, unlike other prospective randomized studies in which sojutsu (containing Atractylodes lancea rhizome) Goreisan was used. The overall recurrence rate was 11.4% (13/114: 10 for Group N, 2 for Group G, and 1 for Group S). The recurrence rate of Group G was significantly lower than that of Group N (5.4% vs 25.6%; P = .043). The recurrence rate of Group S was also significantly lower than that of Group N (2.6% vs 25.6%; P = .02). No patients developed complications associated with the administration of Kampo medicine. CONCLUSION: This is the first study to show that Kampo medicine reduced the recurrence rate of CSDH in an overall population. This study demonstrated that byakujutsu Goreisan and Saireito may have favorable effects, unlike other studies, because byakujutsu has stronger anti-inflammatory activity than sojutsu.

Electrical stimulation mitigates muscle degradation shift in gene expressions during 12-h mechanical ventilation.

Ventilator-induced diaphragm dysfunction (VIDD), a dysfunction of the diaphragm muscle caused by prolonged mechanical ventilation (MV), is an important factor that hinders successful weaning from ventilation. We evaluated the effects of electrical stimulation of the diaphragm muscle (pulsed current with off-time intervals) on genetic changes during 12 h of MV (E-V12). Rats were divided into four groups: control, 12-h MV, sham operation, and E-V12 groups. Transcriptome analysis using an RNA microarray revealed that 12-h MV caused upregulation of genes promoting muscle atrophy and downregulation of genes facilitating muscle synthesis, suggesting that 12-h MV is a reasonable method for establishing a VIDD rat model. Of the genes upregulated by 12-h MV, 18 genes were not affected by the sham operation but were downregulated by E-V12. These included genes related to catabolic processes, inflammatory cytokines, and skeletal muscle homeostasis. Of the genes downregulated by 12-h MV, 6 genes were not affected by the sham operation but were upregulated by E-V12. These included genes related to oxygen transport and mitochondrial respiration. These results suggested that 12-h MV shifted gene expression in the diaphragm muscle toward muscle degradation and that electrical stimulation counteracted this shift by suppressing catabolic processes and increasing mitochondrial respiration.

Liver regeneration after portal vein embolization: comparison between absolute ethanol and N-butyl-cyanoacrylate in an in vivo rat model.

PURPOSE: To compare the effects of absolute ethanol (ethanol) and N-butyl-cyanoacrylate (NBCA) on non-embolized liver lobe regeneration in a rat model. METHODS: Twenty-seven Sprague-Dawley rats underwent portal vein embolization (PVE) using ethanol:lipiodol, 1:1 (ethanol group, n = 11, 40.74%), NBCA:lipiodol, 1:1 (NBCA group, n = 11, 40.74%), or sham treatment (sham group, n = 5, 18.52%). The non-embolized and embolized lobe-to-whole liver weight ratios 14 days after PVE were compared among the groups (n = 5, 18.52%). The expressions of CD68 and Ki-67 and embolized-lobe necrotic area percentages one day after PVE were compared between the ethanol (n = 3, 11.11%) and NBCA (n = 3, 11.11%) groups. RESULTS: The non-embolized lobe-to-whole liver weight ratio after PVE was significantly higher in the NBCA group (n = 5, 33.33%) than in the ethanol group (n = 5, 33.33%) (84.28% ± 1.53% vs. 76.88% ± 4.12%, P = 0.029). The embolized lobe-to-whole liver weight ratio after PVE was significantly lower in the NBCA group than in the ethanol group (15.72% ± 1.53% vs. 23.12% ± 4.12%, P = 0.029). The proportions of CD68- and Ki-67-positive cells in the non-embolized lobe after PVE were significantly higher in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [60 (48-79) vs. 55 (37-70), P = 0.003; 1 (0-2) vs. 1 (0-2), P = 0.004]. The embolized-lobe necrotic area percentage after PVE was significantly larger in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [29.46 (12.56-83.90%) vs. 16.34 (3.22-32.0%), P < 0.001]. CONCLUSION: PVE with NBCA induced a larger necrotic area in the embolized lobe and promoted greater non-embolized liver lobe regeneration compared with PVE with ethanol.

Interleukin-13 enhanced Ca2+ oscillations in airway smooth muscle cells.

Physiological mechanisms associated with interleukin-13 (IL-13), a key cytokine in asthma, in intracellular Ca(2+) signaling in airway smooth muscle cells (ASMCs) remain unclear. The aim of this study was to assess effects of IL-13 on Ca(2+) oscillations in response to leukotriene D4 (LTD4) in human cultured ASMCs. LTD4-induced Ca(2+) oscillations in ASMCs pretreated with IL-13 were imaged by confocal microscopy. mRNA expressions of cysteinyl leukotriene 1 receptors (CysLT1R), CD38, involved with the ryanodine receptors (RyR) system, and transient receptor potential canonical (TRPC), involved with store-operated Ca(2+) entry (SOCE), were determined by real-time PCR. In IL-13-pretreated ASMCs, frequency of LTD4-induced Ca(2+) oscillations and number of oscillating cells were significantly increased compared with untreated ASMCs. Both xestospongin C, a specific inhibitor of inositol 1,4,5-triphosphate receptors (IP(3)R), and ryanodine or ruthenium red, inhibitors of RyR, partially blocked LTD4-induced Ca(2+) oscillations. Ca(2+) oscillations were almost completely inhibited by 50 µM of 2-aminoethoxydiphenyl borate (2-APB), which dominantly blocks SOCE but not IP(3)R at this concentration. Pretreatment with IL-13 increased the mRNA expressions of CysLT1R and CD38, but not of TRPC1 and TRPC3. We conclude that IL-13 enhances frequency of LTD4-induced Ca(2+) oscillations in human ASMCs, which may be cooperatively modulated by IP(3)R, RyR systems and possibly by SOCE.

Uncontrolled calcium sparks act as a dystrophic signal for mammalian skeletal muscle.

Most excitable cells maintain tight control of intracellular Ca(2+) through coordinated interaction between plasma membrane and endoplasmic or sarcoplasmic reticulum. Quiescent sarcoplasmic reticulum Ca(2+) release machinery is essential for the survival and normal function of skeletal muscle. Here we show that subtle membrane deformations induce Ca(2+) sparks in intact mammalian skeletal muscle. Spontaneous Ca(2+) sparks can be reversibly induced by osmotic shock, and participate in a normal physiological response to exercise. In dystrophic muscle with fragile membrane integrity, stress-induced Ca(2+) sparks are essentially irreversible. Moreover, moderate exercise in mdx muscle alters the Ca(2+) spark response. Thus, membrane-deformation-induced Ca(2+) sparks have an important role in physiological and pathophysiological regulation of Ca(2+) signalling, and uncontrolled Ca(2+) spark activity in connection with chronic activation of store-operated Ca(2+) entry may function as a dystrophic signal in mammalian skeletal muscle.

Direct causality between single-Purkinje cell activities and motor learning revealed by a cerebellum-machine interface utilizing VOR adaptation paradigm.

A cerebellum-machine interface (CMI) was developed to test direct causality between single-unit cerebellar Purkinje cell activities and motor learning. The CMI converts Purkinje cell simple spike firing rates into a pulse width modulation signal that drives a single-joint robot arm. The CMI has no adaptive capability, thus any changes observed in the robot arm motion can be attributed directly to changes in the Purkinje cell's firing activities. We employed a vestibuloocular reflex (VOR) adaptation paradigm in goldfish as an example of motor learning where desired motion and control error signal of the robot arm were given to the fish as its head rotation and retinal slip, respectively. It is demonstrated that the control error of the robot arm decreased gradually, but not monotonically and in many cases only in one direction. This is the first direct evidence that a single Purkinje cell is capable of adaptive motor control. The results also suggest that a single Purkinje cell can be responsible for directional selective VOR motor learning previously reported in goldfish by Yoshikawa et al. (Conf Proc IEEE Eng Med Biol Soc 1:478-481, 2004) and monkeys by Hirata et al. (J Neurophysiol 85(5):2267-2288, 2002).

Temporal changes in accommodative responses to periodic visual motion.

When we shift our gaze to stare at objects at various distances, not only eye positions but also lens accommodation changes. Usually, visually induced accommodation responses (AccRes) present longer latency than accompanying eye movements, resulting in a brief period of an unfocused retinal image after each gaze shift. Unfocused periods may be extended further when the eyes are under predictive control in response to a temporally periodic visual stimulus. It has been shown that phase lag of the AccRes shortened when the visual target motion was temporally periodic, contributing to reduction of the unfocused periods. However, how rapidly the phase lag shortening is acquired or how long the shortened phase is maintained has been unknown. Presently, we aimed at clarifying the acquisition and maintenance characteristics of the AccRes adaptation. Experiments employing periodic accommodative stimuli revealed that the phase lag is shortened and the gain is temporarily (for 1.3-4 s) increased as early as in the 2nd cycle of the stimulation. Moreover, we show that the adapted AccRes persist for at least 0.25 s in addition to the latency (0.35 s) in the dark after removing periodic visual stimulation. These results add new insights into the temporal characteristics of AccRes adaptation and its maintenance that would play an important role in our daily visual experiences.

Asymmetric posterior reversible encephalopathy syndrome secondary to epilepsy occurring in the chronic phase of subarachnoid hemorrhage.

Background: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical syndrome that refers to a disorder with reversible subcortical vasogenic brain edema involving the parieto-occipital lobe, temporal lobe, basal ganglia, and its surroundings. Radiologically, it is characterized by symmetrical lesions; however, atypical findings have sometimes been reported. Case Description: A 79-year-old woman experienced subarachnoid hemorrhage (SAH) a year and a half previously before this hospitalization. She presented with sudden-onset coma, dacryorrhea, and moderate right hemiparesis and was taken to our hospital. Computed tomography showed no apparent abnormal acute lesions. Electroencephalography confirmed periodic lateralized epileptiform discharges in the left hemisphere. First, based on the findings, she was diagnosed with nonconvulsive status epilepticus and started antiepileptic therapy. Six days after admission, however, multiple asymmetric lesions were confirmed on magnetic resonance imaging. Considering that findings subsequently improved, we finally diagnosed her with asymmetric PRES secondary to epilepsy occurring in the chronic phase of SAH. Aphasia and right hemispatial neglect persisted as sequelae and she was transferred to a rehabilitation hospital with a modified Rankin scale of 3. Conclusion: Excessive elevation of blood flow in the hemisphere is inferred to lead to blood-brain barrier collapse and subsequent asymmetric PRES.