Assessment of objective visual function following idebenone administration in patients with leber hereditary optic neuropathy.

PURPOSE: To objectively assess visual function in Leber's Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage. STUDY DESIGN: A descriptive study involving four confirmed LHON patients. METHODS: Four patients received 900 mg/day of oral idebenone for 24 weeks. Baseline and post-treatment visual acuity, visual fields, and BOLD fMRI responses while passively viewed drifting contrast pattern visual stimuli were compared with self-reported symptoms. RESULTS: Post-idebenone, one patient showed positive trends across subjective tests, reported symptoms, and fMRI. Two patients had stable symptoms and fMRI responses; one improved on subjective tests, and another worsened slightly. Another patient improved in visual field tests despite worsening symptoms and fMRI trends. CONCLUSION: fMRI may offer a valuable objective measure of visual functions in LHON and appears to be more relevant in assessing symptoms. Further research with more participants is needed to ascertain fMRI's role in developing objective visual assessments and treatment evaluation.

Perioperative serum syndecan-1 concentrations in patients who underwent cardiovascular surgery with cardiopulmonary bypass and its association with the occurrence of postoperative acute kidney injury: a retrospective observational study.

BACKGROUND: Various factors can cause vascular endothelial damage during cardiovascular surgery (CVS) with cardiopulmonary bypass (CPB), which has been suggested to be associated with postoperative complications. However, few studies have specifically investigated the relationship between the degree of vascular endothelial damage and postoperative acute kidney injury (pAKI). The objectives of this study were to measure perioperative serum syndecan-1 concentrations in patients who underwent CVS with CPB, evaluate their trends, and determine their association with pAKI. METHODS: This was a descriptive and case‒control study conducted at the National University Hospital. Adult patients who underwent CVS with CPB at a national university hospital between March 15, 2016, and August 31, 2020, were included. Patients who were undergoing preoperative dialysis, had preoperative serum creatinine concentrations greater than 2.0 mg dl-1, who were undergoing surgery involving the descending aorta were excluded. The perioperative serum syndecan-1 concentration was measured, and its association with pAKI was investigated. RESULTS: Fifty-two patients were included. pAKI occurred in 18 (34.6%) of those patients. The serum syndecan-1 concentration increased after CPB initiation and exhibited bimodal peak values. The serum syndecan-1 concentration at all time points was significantly elevated compared to that after the induction of anesthesia. The serum syndecan-1 concentration at 30 min after weaning from CPB and on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.10 [1.01 to 1.21], P = 0.03]; OR = 1.16 [1.01 to 1.34], P = 0.04]; and the cutoff values of the serum syndecan-1 concentration that resulted in pAKI were 101.0 ng ml-1 (sensitivity = 0.71, specificity = 0.62, area under the curve (AUC) = 0.67 (0.51 to 0.83)) and 57.1 ng ml-1 (sensitivity = 0.82, specificity = 0.56, AUC = 0.71 (0.57 to 0.86)). Multivariate logistic regression analysis revealed that the serum syndecan-1 concentration on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.02 [1.00 to 1.03]; P = 0.03). CONCLUSION: The serum syndecan-1 concentration at all time points was significantly greater than that after the induction of anesthesia. The serum syndecan-1 concentration on postoperative day 1 was significantly associated with the occurrence of pAKI. TRIAL REGISTRATION: This study is not a clinical trial and is not registered with the registry.

Endovascular treatment of an aneurysm arising from the minor limb of an upper basilar artery fenestration: illustrative case.

BACKGROUND: An aneurysm arising in an upper basilar artery (BA) fenestration is extremely rare. The authors reported a case involving successful endovascular treatment of an aneurysm arising from the minor limb of an upper BA fenestration. OBSERVATIONS: A 65-year-old woman presented with an incidentally detected upper BA aneurysm arising from the minor limb of an upper BA fenestration. The irregularly shaped aneurysm was 6.0 × 2.7 mm in diameter, and the minor limb had several perforators. The aneurysm was nearly completely occluded with a catheter-assisted technique. The authors preserved both limbs of the BA fenestration. The postoperative course was uneventful, and the patient had an excellent clinical course with no neurological deficits or aneurysmal recanalization. LESSONS: The case is the first report of an unruptured aneurysm arising at the minor limb of an upper BA fenestration. In this case, the authors preserved the minor limb with endovascular treatment. The authors believe catheter-assisted coil embolization to be a feasible endovascular technique in such cases.

Association between relational mobility, brain structure, and prosociality in adolescents.

Trust plays a vital role in human society. Previous studies have suggested that trust comprises general trust and caution. General trust is a belief that others, in general, are trustworthy, and caution is a belief in the importance of vigilance in dealing with others. Adolescence is a critical period for establishing these psychological traits. It is a period of physical and mental development, and the social environment during this period influences adolescents' psychology, including their brain structures. In this study, we focus on relational mobility as a socio-environmental factor that influences the development of adolescents' psychology and the brain. Relational mobility refers to the degree of freedom to choose and replace social relationships and consists of two subfactors (the degree of freedom to choose and replace social relationships and the number of opportunities to meet new people). Accordingly, we analyzed each subfactor separately. Results showed that the degree of freedom to choose and replace social relationships was only negatively associated with caution and left posterior superior temporal gyrus (pSTG) volume in adolescents. Furthermore, the effect of the freedom to choose and replace social relationships on caution was significantly relevant to the left pSTG volume. In contrast, the degree of opportunities to meet new people was associated with neither general trust nor caution, whereas it was positively associated with the right supramarginal gyrus volume. This study suggests that the social environment during adolescence influences brain structures related to prosociality.

Association of Cardiovascular Risk Markers and Fitness with Task-Related Neural Activity during Animacy Perception.

PURPOSE: Numerous studies have demonstrated the association between cardiovascular risk markers and fitness, and broad aspects of cognition; however, the possible association of cardiovascular risk markers and fitness with social cognition, which plays a significant role in the development and maintenance of social relationships, has largely been ignored. Herein, we investigated the relationship of cardiovascular risk markers and fitness with task-related neural activity during animacy perception. METHODS: We analyzed data from the Human Connectome Project derived from 1027 adults age 22-37 yr. Canonical correlation analysis (CCA) was conducted to evaluate the association between participants' body mass index, systolic and diastolic blood pressure, submaximal endurance, gait speed, hand dexterity, and muscular strength with task-related neural activity during animacy perception. RESULTS: We observed a single significant CCA mode. Body mass index and blood pressure demonstrated negative cross-loadings with task-related neural activity in the temporoparietal, superior and anterior temporal, posterior cingulate, and inferior frontal regions, whereas submaximal endurance, hand dexterity, and muscular strength demonstrated positive cross-loadings. The observed CCA variates did not seem highly heritable, as the absolute differences in CCA variates in monozygotic twins, dizygotic twins, and nontwin siblings were not statistically different. Furthermore, the cardiovascular risk markers and fitness CCA variates were positively associated with animacy perception and emotion recognition accuracy, which was mediated by the task-related neural activity. CONCLUSIONS: The present findings can provide new insights into the role of markers for cardiovascular health and fitness, specifically their association with social cognition and the underlying neural basis. The intervention for cardiovascular risk and fitness could be a potentially cost-effective method of targeting social cognition.

Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma.

Purpose: Glaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma. Methods: We collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects. Results: In the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level. Conclusions: Our results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.

Childhood exercise predicts response inhibition in later life via changes in brain connectivity and structure.

Participation in exercise during early life (i.e., childhood through adolescence) enhances response inhibition; however, it is unclear whether participation in exercise during early life positively predicts response inhibition in later life. This historical cohort study was designed to clarify whether participation in exercise (e.g., structured sports participation) during early life predicts response inhibition in adulthood and if so, to reveal the brain connectivity and cortical structures contributing to this association. We analyzed data derived from 214 participants (women = 104, men = 110; age: 26‒69 years). Results indicated that participation in exercise during childhood (before entering junior high school; ≤ 12 years old) significantly predicted better response inhibition. No such association was found if exercise participation took place in early adolescence or later (junior high school or high school; ≥ 12 years old). The positive association of exercise participation during childhood with response inhibition was moderated by decreased structural and functional connectivity in the frontoparietal (FPN), cingulo-opercular (CON), and default mode networks (DMN), and increased inter-hemispheric structural networks. Greater cortical thickness and lower levels of dendritic arborization and density in the FPN, CON, and DMN also moderated this positive association. Our results suggest that participation in exercise during childhood positively predicts response inhibition later in life and that this association can be moderated by changes in neuronal circuitry, such as increased cortical thickness and efficiency, and strengthened inter-hemispheric connectivity.

Brain/MINDS beyond human brain MRI project: A protocol for multi-level harmonization across brain disorders throughout the lifespan.

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing measurement procedures, developing and analyzing neuroimaging protocols, and databasing are done at three research sites. A high-quality scanning protocol, Harmonization Protocol (HARP), was established for five high-quality 3 T scanners to obtain multimodal brain images including T1 and T2-weighted, resting-state and task functional and diffusion-weighted MRI. Data are preprocessed and analyzed using approaches developed by the Human Connectome Project. Preliminary results in 30 TS demonstrated cortical thickness, myelin, functional connectivity measures are comparable across 5 scanners, suggesting sensitivity to subject-specific connectome. A total of 75 TS and more than two thousand patients with various psychiatric and neurological disorders are scheduled to participate in the project, allowing a mixed model statistical harmonization. The HARP protocols are publicly available online, and all the imaging, demographic and clinical information, harmonizing database will also be made available by 2024. To the best of our knowledge, this is the first project to implement a prospective, multi-level harmonization protocol with multi-site TS data. It explores intractable brain disorders across the lifespan and may help to identify the disease-specific pathophysiology and imaging biomarkers for clinical practice.

V1 Projection Zone Signals in Human Macular Degeneration Depend on Task Despite Absence of Visual Stimulus.

Identifying the plastic and stable components of the visual cortex after retinal loss is an important topic in visual neuroscience and neuro-ophthalmology.1-5 Humans with juvenile macular degeneration (JMD) show significant blood-oxygen-level-dependent (BOLD) responses in the primary visual area (V1) lesion projection zone (LPZ),6 despite the absence of the feedforward signals from the degenerated retina. Our previous study7 reported that V1 LPZ responds to full-field visual stimuli during the one-back task (OBT), not during passive viewing, suggesting the involvement of task-related feedback signals. Aiming to clarify whether visual inputs to the intact retina are necessary for the LPZ responses, here, we measured BOLD responses to tactile and auditory stimuli for both JMD patients and control participants with and without OBT. Participants were instructed to close their eyes during the experiment for the purpose of eliminating retinal inputs. Without OBT, no V1 responses were detected in both groups of participants. With OBT, to the contrary, both stimuli caused substantial V1 responses in JMD patients, but not controls. Furthermore, we also found that the task-dependent activity in V1 LPZ became less pronounced when JMD patients opened their eyes, suggesting that task-related feedback signals can be partially suppressed by residual feedforward signals. Modality-independent V1 LPZ responses only in the task condition suggest that V1 LPZ responses reflect task-related feedback signals rather than reorganized feedforward visual inputs.

Characteristics of Japanese patients with Leber's hereditary optic neuropathy and idebenone trial: a prospective, interventional, non-comparative study.

PURPOSE: Leber's hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients. STUDY DESIGN: Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939. METHODS: Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout. RESULTS: Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%). CONCLUSION: Idebenone's potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.

Successful application of the snare technique for the deployment of the proximal portion of a Zenith Alpha Thoracic Endovascular Graft: a case report.

BACKGROUND: Open surgery can be required or even fatal if incomplete deployment of stent graft (SG) occurs. We herein report the first case in which a snare was successfully used to perform endovascular therapeutic troubleshooting on the proximal portion of a Zenith Alpha thoracic endovascular graft proximal component that showed incomplete deployment. CASE PRESENTATION: The patient was an 80-year-old woman. She underwent thoracic endovascular aortic repair (TEVAR) for subacute phase Stanford type B ulcer-like projection aortic dissection. Although the ulcer-like projection disappeared, a follow-up computed tomography angiogram (CTA) obtained approximately 1 year postoperatively showed type Ia and Ib endoleaks. Since there is a high risk of rupture as the aneurysm diameter increases, we determined that an additional SG was indicated. An attempt was made to place the SG in Zone 3, but as the lesser curvature side of the proximal portion stopped in a position that was perpendicular to the vascular wall (downward facing), the SG proximal portion did not completely expand. A guiding sheath was inserted into the aortic arch via the left brachial artery, and, using a snare that we inserted via the femoral artery, we grasped the guiding sheath. A catheter and guidewire (GW) were inserted via the guiding sheath and then rotated under the lesser curvature of the SG proximal portion; the GW was then passed through the loop of the snare. This allowed us to insert the hard loop structure under the SG proximal portion, which in turn allowed successful repair of the incomplete deployment of the SG. Type Ia and Ib endoleaks remained but were less than those before additional TEVAR. One week later, she was discharged. One year later, CT showed no interval change in the size of aortic aneurysm with dissection, and she has been followed on an outpatient basis. CONCLUSIONS: When the endovascular diameter of the proximal aortic arch is large, incomplete deployment of the proximal portion of a Zenith Alpha thoracic endovascular graft can occur, but bailout is possible through the use of the snare technique as endovascular therapy.

Identification of the brain networks that contribute to the interaction between physical function and working memory: An fMRI investigation with over 1,000 healthy adults.

There is a growing consensus regarding the positive relationship between physical function and working memory; however, explanations of task-evoked functional activity regarding this relationship and its differences in physical function domains remain controversial. This study illustrates the cross-sectional relationships between cardiorespiratory fitness, gait speed, hand dexterity, and muscular strength with working memory task (N-back task) performance and the mediating effects of task-evoked functional activity in 1033 adults aged between 22 and 37 years. The results showed that cardiorespiratory fitness and hand dexterity were independently associated with N-back task performance to a greater extent and in contrast to gait speed and muscular strength. These relationships were mediated by task-evoked functional activity in a part of the frontoparietal network (FPN) and default mode network (DMN). Superior cardiorespiratory fitness could contribute to working memory performance by enhancing the compensational role of FPN-related broader region activation. Hand dexterity was associated with moderation of the interaction in terms of task-evoked activation between the FPN and DMN, which in turn, improved N-back task performance. Based on these findings, we conclude that cardiorespiratory fitness and hand dexterity have common and unique mechanisms enhancing working memory.

Dynamic Light Scattering Measurements for Soft Materials on Solid Substrates: Employing Evanescent-wave Illumination and Dark-field Collection with a High Numerical Aperture Microscope Objective.

We developed an instrument that allows us to measure dynamic light scattering from soft materials on solid substrates by avoiding strong background due to the reflection light from substrates. In the instrument, samples on substrates are illuminated by evanescent-light field and the resultant scattered light from the samples is collected with a dark-field optical configuration by employing a high numerical aperture microscope objective. We applied the instrument to measure the dynamic properties of supported lipid bilayers (SLBs), which have been widely utilized in industries as functional materials such as biosensors. From the time course of the scattered light from the SLBs, the power spectrum with the broad peak ranging from 10 to 20 kHz is observed. The use of the microscope objectives enables us to apply the instrument to future light scattering imaging for dynamic properties of soft materials supported on various substrates by combining with conventional microscope systems.

Cortical Regions Encoding Hardness Perception Modulated by Visual Information Identified by Functional Magnetic Resonance Imaging With Multivoxel Pattern Analysis.

Recent studies have revealed that hardness perception is determined by visual information along with the haptic input. This study investigated the cortical regions involved in hardness perception modulated by visual information using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). Twenty-two healthy participants were enrolled. They were required to place their left and right hands at the front and back, respectively, of a mirror attached to a platform placed above them while lying in a magnetic resonance scanner. In conditions SFT, MED, and HRD, one of three polyurethane foam pads of varying hardness (soft, medium, and hard, respectively) was presented to the left hand in a given trial, while only the medium pad was presented to the right hand in all trials. MED was defined as the control condition, because the visual and haptic information was congruent. During the scan, the participants were required to push the pad with the both hands while observing the reflection of the left hand and estimate the hardness of the pad perceived by the right (hidden) hand based on magnitude estimation. Behavioral results showed that the perceived hardness was significantly biased toward softer or harder in >73% of the trials in conditions SFT and HRD; we designated these trials as visually modulated (SFTvm and HRDvm, respectively). The accuracy map was calculated individually for each of the pair-wise comparisons of (SFTvm vs. MED), (HRDvm vs. MED), and (SFTvm vs. HRDvm) by a searchlight MVPA, and the cortical regions encoding the perceived hardness with visual modulation were identified by conjunction of the three accuracy maps in group analysis. The cluster was observed in the right sensory motor cortex, left anterior intraparietal sulcus (aIPS), bilateral parietal operculum (PO), and occipito-temporal cortex (OTC). Together with previous findings on such cortical regions, we conclude that the visual information of finger movements processed in the OTC may be integrated with haptic input in the left aIPS, and the subjective hardness perceived by the right hand with visual modulation may be processed in the cortical network between the left PO and aIPS.

Diffusivity and quantitative T1 profile of human visual white matter tracts after retinal ganglion cell damage.

In patients with retinal ganglion cell diseases, recent diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts such as the optic tract, and optic radiation. However, the microstructural origin of these diffusivity changes is unknown as DTI metrics involve multiple biological factors and do not correlate directly with specific microstructural properties. In contrast, recent quantitative T1 (qT1) mapping methods provide tissue property measurements relatively specific to myelin volume fractions in white matter. This study aims to improve our understanding of microstructural changes in visual white matter tracts following retinal ganglion cell damage in Leber's hereditary optic neuropathy (LHON) patients by combining DTI and qT1 measurements. We collected these measurements from seven LHON patients and twenty age-matched control subjects. For all individuals, we identified the optic tract and the optic radiation using probabilistic tractography, and evaluated diffusivity and qT1 profiles along them. Both diffusivity and qT1 measurements in the optic tract differed significantly between LHON patients and controls. In the optic radiation, these changes were observed in diffusivity but were not evident in qT1 measurements. This suggests that myelin loss may not explain trans-synaptic diffusivity changes in the optic radiation as a consequence of retinal ganglion cell disease.

Grafting as a Tool for Study of Phototropism in Phycomyces.

Physiological responses, such as phototropism and carotenogenesis, are usually exhibited through a specific cascade composed of several gene functions. The number of such gene functions can be determined by means of complementation analysis. For this purpose, a procedure is needed to produce heterokaryons easily and with a high success rate. Here, we present a method of grafting sporangiophores from different mutants to obtain heterokaryotic regenerates at the graft union, based on the large size of the sporangiophore and its remarkable regeneration capability.

Age-related macular degeneration affects the optic radiation white matter projecting to locations of retinal damage.

We investigated the impact of age-related macular degeneration (AMD) on visual acuity and the visual white matter. We combined an adaptive cortical atlas and diffusion-weighted magnetic resonance imaging (dMRI) and tractography to separate optic radiation (OR) projections to different retinal eccentricities in human primary visual cortex. We exploited the known anatomical organization of the OR and clinically relevant data to segment the OR into three primary components projecting to fovea, mid- and far-periphery. We measured white matter tissue properties-fractional anisotropy, linearity, planarity, sphericity-along the aforementioned three components of the optic radiation to compare AMD patients and controls. We found differences in white matter properties specific to OR white matter fascicles projecting to primary visual cortex locations corresponding to the location of retinal damage (fovea). Additionally, we show that the magnitude of white matter properties in AMD patients' correlates with visual acuity. In sum, we demonstrate a specific relation between visual loss, anatomical location of retinal damage and white matter damage in AMD patients. Importantly, we demonstrate that these changes are so profound that can be detected using magnetic resonance imaging data with clinical resolution. The conserved mapping between retinal and white matter damage suggests that retinal neurodegeneration might be a primary cause of white matter degeneration in AMD patients. The results highlight the impact of eye disease on brain tissue, a process that may become an important target to monitor during the course of treatment.