Effects of Gadolinium Retention in the Brains of Type 2 Diabetic Rats after Repeated Administration of Gadolinium-Based MRI Contrast Agents on Neurobiology and NLRP3 Inflammasome Activation.

BACKGROUND: The neurotoxic potential of gadolinium (Gd)-based contrast agents (GBCAs) retention in the brains of patients with type 2 diabetes mellitus (T2DM) is unclear. PURPOSE: To determine the deposition and clearance of GBCAs in T2DM rats and the mechanism by which Gd enhances nucleotide-binding oligomerization domain-3 (NLRP3) inflammasome activation. STUDY TYPE: Cross-sectional, prospective. ANIMAL MODEL: 104 T2DM male Wistar rats. FIELD STRENGTH/SEQUENCE: 9.4-T, T1-weighted fast spin echo sequence. ASSESSMENT: T2DM (male Wistar rats, n = 52) and control group (healthy, male Wistar rats, n = 52) rats received saline, gadodiamide, Gd-diethylenetriaminepentaacetic acid, and gadoterate meglumine for four consecutive days per week for 7 weeks. The distribution and clearance of Gd in the certain brain were assessed by MRI (T1 signal intensity and relaxation rate R1, on the last day of each week), inductively coupled plasma mass-spectroscopy, ultraperformance liquid chromatography mass spectrometry, and transmission electron microscopy. Behavioral tests, histopathological features, and the effects of GBCAs on neuroinflammation were also analyzed. STATISTICAL TESTS: One-way analysis of variance, bonferroni method, and unpaired t-test. A P-value <0.05 was considered statistically significant. RESULTS: The movement distance and appearance time in the open field test of the T2DM rats in the gadodiamide group were significantly shorter than in the other groups. Furthermore, the expression of NLRP3, Pro-Caspase-1, interleukin-1ß (IL-1ß), and apoptosis-associated speck-like protein containing a CARD protein in neurons was significantly higher in the gadodiamide group than in the saline group, as shown by Western blot. Gadodiamide also induced differentiation of microglia into M1 type, decreased the neuronal mitochondrial membrane potential, and significantly increased neuronal apoptosis from flow cytometry. DATA CONCLUSION: T2DM may affect both the deposition and clearance of GBCAs in the brain. Informed by the T2DM model, gadodiamide could mediate the neuroinflammatory response by NLRP3 inflammasome activation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

GelMA-MXene hydrogel nerve conduits with microgrooves for spinal cord injury repair.

Repair of spinal cord injury (SCI) depends on microenvironment improvement and the reconnection between injured axons and regenerated neurons. Here, we fabricate a GelMA-MXene hydrogel nerve conduit with electrical conductivity and internal-facing longitudinal grooves and explore its function in SCI repair. It is found that the resultant grooved GelMA-MXene hydrogel could effectively promote the neural stem cells (NSCs) adhesion, directed proliferation and differentiation in vitro. Additionally, when the GelMA-MXene conduit loaded with NSCs (GMN) is implanted into the injured spinal cord site, effective repair capability for the complete transection of SCI was demonstrated. The GMN group shows remarkable nerve recovery and significantly higher BBB scores in comparison to the other groups. Therefore, GMN with the microgroove structure and loaded with NSCs is a promising strategy in treating SCI.

Efficacy and Safety of Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Liver Disease: a Meta-Analysis and Systematic Review.

BACKGROUND: Liver disease is associated with increased bleeding risk. The efficacy and safety of direct oral anticoagulants (DOACs) is a subject of contention in atrial fibrillation (AF) patients with liver disease. METHODS: Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus warfarin in AF patients with liver disease from January 1980 to April 2020. A meta-analysis was conducted using a random-effects model. RESULTS: Six studies involving 41,859 patients were included. Compared with warfarin, DOACs demonstrated significant reduction in ischemic stroke (HR, 0.68; 95% CI (0.54-0.86)), major bleeding (0.74 (0.59-0.92)), and intracranial hemorrhage (ICH) (0.48 (0.40-0.58)), with no significant effect on gastrointestinal bleeding (P = 0.893) in AF patients with liver disease. Similar results were observed in regular-dose, reduced-dose, and active liver disease subgroups, albeit Asian patients had a slight reduction in major bleeding (P = 0.055). Furthermore, the pooled estimates of individual DOAC subgroups indicated that dabigatran and apixaban led to greater safety in major bleeding (P < 0.001), ICH (P < 0.001), and gastrointestinal bleeding (P < 0.005) in these patients. The same trends were observed in AF patients with cirrhosis. CONCLUSIONS: Our findings suggest that DOACs significantly reduce the risk of ischemic stroke, major bleeding, and ICH, with no significant effect on the risk of gastrointestinal bleeding in AF patients with liver disease compared with warfarin.

Oxygen-defect-dependent ferromagnetism and strain modulation in free-standing two-dimensional TiO2 monolayers.

Recently, layered two-dimensional titania (2D-TiO2) with a reduced band gap has been successfully synthesized. However, as an important application in spintronics, ferromagnetism in this material has not been investigated so far. To obtain the expected ferromagnetism, the formation and stability of the most prominent oxygen defects in a TiO2 monolayer under different external strains were explored systematically. The calculated results disclosed that structural deformation induced by tensile strain not only led to changes in the oxygen defect formation energy but also modified its magnetic features. With an increase in compressed strain, the Curie temperature in this system decreased due to insufficient spin polarization. Our calculations provide a strategy to utilize oxygen defect and strain engineering to realize applications of 2D TiO2 monolayers in spintronics.

Highly Efficient Glioma Targeting of Tat Peptide-TTA1 Aptamer-Polyephylene Glycol-Modified Gelatin-Siloxane Nanoparticles.

Gliomas are the most common type of intracranial malignant tumor; however, current treatment approaches are often ineffective due to limited penetration of genes or drugs through the blood-brain barrier (BBB). Here we describe the synthesis of gelatin-siloxane nanoparticles (GS NPs) as candidate gene carriers through a two-step sol-gel process. To increase the efficiency of glioma targeting, human immunodeficiency virus-derived Tat, tumor-targeting aptamer (TTA)1, and polyethylene glycol (PEG) were conjugated to the GS NPs to generate Tat-TTA1-PEG-GS NPs. In vivo imaging revealed that these modified NPs not only evaded capture by the reticulo-endothelial system, but were able to cross the BBB to reach gliomas. Our results suggest that Tat-TTA1-PEG-GS NPs are a new type of non-viral vector that can deliver therapeutic DNA or drugs for highly efficient glioma treatment.

The Characteristic and Short-Term Prognosis of Tinnitus Associated with Sudden Sensorineural Hearing Loss.

Tinnitus is believed to result from the maladaptive plasticity of the auditory nervous system; reports regarding its severity and prognosis are conflicting. We evaluated the characteristic and short-term prognosis of tinnitus associated with sudden sensorineural hearing loss (SSNHL). A total of 230 cases were enrolled. The severity and 1-month prognosis of tinnitus (according to the Tinnitus Handicap Inventory (THI)) were assessed in terms of the patients' sex, age, level of hearing loss, type of audiogram results, and so on. According to our statistical analysis, the degree of handicap due to tinnitus was not related to sex, age, or level of hearing loss; the Tinnitus Handicap Inventory indicated that the low-frequency-audiogram group had a low tinnitus handicap (F = 7.516, P = 0.000). Furthermore, we found that the prognosis of tinnitus was not related to the type of audiogram or level of hearing loss. Recovery from a severe level of hearing loss was, however, found to be associated with a poor tinnitus prognosis (F = 5.203, P = 0.006). In summary, our study indicates that the association between tinnitus and SSNHL is extremely high. Tinnitus can be ameliorated by the successful treatment of hearing loss. The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800014797).

[Regional homogeneity changes in patients with obstructive sleep apnea-hypopnea syndrome: resting-state functional MRI study].

OBJECTIVE: To investigate the change of regional homogeneity (ReHo) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) using resting-state functional magnetic resonance imaging(fMRI). METHODS: Resting-state fMRI data were collected from 15 patients with OSAHS and 15 normal controls. Patients were enrolled from the Sleep Laboratory of the Otolaryngology-Head and Neck Surgery Department of Zhongda Hospital, Southeast University, Nanjing from November 2014 to June 2015. The data were analyzed with the ReHo method and compared between OSAHS and controls. RESULTS: The ReHo showed a significant increase in the posterior lobe of right cerebellum (t=4.292 1, P<0.01), posterior lobe of left cerebellum (t=4.350 6, P<0.01), right brainstem (t=5.276 6, P<0.01), right occipital lobe (t=3.620 9, P= 0.001), left basal ganglia (t=3.385 6, P=0.002) and left temporal lobe (t=4.781 2, P<0.01) and a decrease in the right middle frontal gyrus (t=-3.564 4, P= 0.001), right inferior parietal lobe (t=-4.123 7, P<0.01) and bilateral superior frontal gyrus (t=-3.500 9, P=0.002) in patients with OSAHS. Furthermore, the average ReHo values of the posterior lobe of bilateral cerebellum was positively correlated with the MMSE scores (r=0.682, P=0.012), the LMT scores (r=0.623, P=0.013) and the LMT-delayed recall scores (r=0.577, P=0.024), while negatively correlated with the TMT-A scores (r=-0.723, P=0.002); the average ReHo values of the right middle frontal gyrus (r=0.661, P=0.007) was positively correlated with the TMT-A scores. CONCLUSION: The current findings indicate that significant changes of ReHo in the global brain regions have been detected in OSAHS patients and the compensatory change of brain function occur. Abnormal ReHo values in the posterior lobe of bilateral cerebellum and right middle frontal gyrus could serve as potential biomarkers for assessment of neuronal damage and further provides insights into the biological mechanism of the disease.

The differentiation of Lgr5+ progenitor cells on nanostructures of self-assembled silica beads.

Supporting cells(SCs) have been demonstrated to be a reliable source for regenerating hair cells(HCs). Previous research has reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo. However, there is limited knowledge about the impact of the material on Lgr5+ cells. In this study, Lgr5+ cells were isolated from neonatal Lgr5-EGFP-CreERT2 transgenic mice by flow cytometry and then plated on self-assembled silica beads (SB). Lgr5+ cell differentiation was observed by immunofluorescence. We found that in the direct differentiation assay, the SB group generated more hair cells than the control group(*p < 0.05). Especially in the SB group, Lgr5+ progenitors generated significantly more Myo7a+ HCs outside of the colony than in the control group(**p < 0.01). In the sphere differentiation assay, we found that the diameter of spheres in the SB group was significantly larger compared to those of the control group(**p < 0.01). However, the difference in the ratio of myo7a+ cell counts was not obvious(P>0.05). The experiment proved that the self-assembled silica beads could promote the differentiation of Lgr5+ progenitors in vitro. Our findings implicate that nanostructures of self-assembled silica beads can be used as vectors for stem cell research in the inner ear.

[Functional magnetic resonance imaging in patients with long-term unilateral hearing loss].

OBJECTIVE: To evaluate the potential functional reorganization by functional magnetic resonance imaging (MRI) to measure the brain activation in responses to stimulation to healthy ears in patients with long-term unilateral hearing loss (UHL). METHODS: From June 1998 to December 2009, 23 patients with serious UHL (15 left, 8 right) were recruited along with 15 matched normal hearing subjects. Laterality index (LI) for activated voxel in primary auditory cortex (PAC) was calculated. And the activations outside auditory cortex were also evaluated. RESULTS: The data were discarded in 3 patients with left-ear UHL and 1 normal subject because of head motion. All control subjects showed contralateral dominant activation of PAC in group analysis. However, the group data of UHL patients showed that the activation was more symmetrical and the contralateral dominance diminished versus the control group. As compared with normal subjects outside PAC, heightened activation in left prefrontal cortex, bilateral inferior parietal lobule and left occipital/precuneus was found in UHL patients while reduced activation in left superior temporal gyrus was also found. CONCLUSIONS: The diminished contralateral dominance in PAC and heightened activation in non-auditory region suggest the reduction of interhemispheral inhibition and general increase in brain excitation in long-term UHL patients potentially occur as a result of functional reorganization adaptive to UHL. However, the reduced activation in superior temporal gyrus may be correlated with the deterioration of speech perception in these patients.

Forward Operator Estimation in Generative Models with Kernel Transfer Operators.

Generative models (e.g., variational autoencoders, flow-based generative models, GANs) usually involve finding a mapping from a known distribution, e.g. Gaussian, to an estimate of the unknown data-generating distribution. This process is often carried out by searching over a class of non-linear functions (e.g., representable by a deep neural network). While effective in practice, the associated runtime/memory costs can increase rapidly, and will depend on the performance desired in an application. We propose a much cheaper (and simpler) strategy to estimate this mapping based on adapting known results in kernel transfer operators. We show that if some compromise in functionality (and scalability) is acceptable, our proposed formulation enables highly efficient distribution approximation and sampling, and offers surprisingly good empirical performance which compares favorably with powerful baselines.

Understanding Uncertainty Maps in Vision with Statistical Testing.

Quantitative descriptions of confidence intervals and uncertainties of the predictions of a model are needed in many applications in vision and machine learning. Mechanisms that enable this for deep neural network (DNN) models are slowly becoming available, and occasionally, being integrated within production systems. But the literature is sparse in terms of how to perform statistical tests with the uncertainties produced by these overparameterized models. For two models with a similar accuracy profile, is the former model's uncertainty behavior better in a statistically significant sense compared to the second model? For high resolution images, performing hypothesis tests to generate meaningful actionable information (say, at a user specified significance level α=0.05) is difficult but needed in both mission critical settings and elsewhere. In this paper, specifically for uncertainties defined on images, we show how revisiting results from Random Field theory (RFT) when paired with DNN tools (to get around computational hurdles) leads to efficient frameworks that can provide a hypothesis test capabilities, not otherwise available, for uncertainty maps from models used in many vision tasks. We show via many different experiments the viability of this framework.

Recent-onset and persistent tinnitus: Uncovering the differences in brain activities using resting-state functional magnetic resonance imaging technologies.

Objective: This study aimed to investigate the differences in intra-regional brain activity and inter-regional functional connectivity between patients with recent-onset tinnitus (ROT) and persistent tinnitus (PT) using resting-state functional magnetic resonance imaging (rs-fMRI), including the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and voxel-wise functional connectivity (FC). Method: We acquired rs-fMRI scans from 82 patients (25 without recent-onset tinnitus, 28 with persistent tinnitus, and 29 healthy controls). Age, sex, and years of education were matched across the three groups. We performed ALFF, ReHo, and voxel-wise FC analyses for all patients. Results: Compared with the control group, participants with ROT and PT manifested significantly reduced ALFF and ReHo activity within the left and right dorsolateral superior frontal gyrus (SFG) and gyrus rectus (GR). Additional voxel-wise FC revealed decreased connectivity between the dorsolateral SFG (left and right) and the right superior parietal gyrus (SPG), right middle frontal gyrus (MFG), and left medial superior frontal gyrus (mSFG) within these two groups. Significant differences were observed between the ROT and PT groups, with the ROT group demonstrating reduced FC. Conclusion: Our data suggest that patients with PT have more difficulty monitoring external stimuli and reorienting attention than patients with ROT. In addition, patients who perceive higher levels of disruption from tinnitus are more likely to develop persistent and debilitating tinnitus once the tinnitus lasts longer than six months. Therefore, we strongly recommend that clinicians implement effective tinnitus management strategies in patients with ROT as soon as possible.

Performing Group Difference Testing on Graph Structured Data From GANs: Analysis and Applications in Neuroimaging.

Generative adversarial networks (GANs) have emerged as a powerful generative model in computer vision. Given their impressive abilities in generating highly realistic images, they are also being used in novel ways in applications in the life sciences. This raises an interesting question when GANs are used in scientific or biomedical studies. Consider the setting where we are restricted to only using the samples from a trained GAN for downstream group difference analysis (and do not have direct access to the real data). Will we obtain similar conclusions? In this work, we explore if "generated" data, i.e., sampled from such GANs can be used for performing statistical group difference tests in cases versus controls studies, common across many scientific disciplines. We provide a detailed analysis describing regimes where this may be feasible. We complement the technical results with an empirical study focused on the analysis of cortical thickness on brain mesh surfaces in an Alzheimer's disease dataset. To exploit the geometric nature of the data, we use simple ideas from spectral graph theory to show how adjustments to existing GANs can yield improvements. We also give a generalization error bound by extending recent results on Neural Network Distance. To our knowledge, our work offers the first analysis assessing whether the Null distribution in "healthy versus diseased subjects" type statistical testing using data generated from the GANs coincides with the one obtained from the same analysis with real data. The code is available at https://github.com/yyxiongzju/GLapGAN.

Graphene Substrates Promote the Differentiation of Inner Ear Lgr5+ Progenitor Cells Into Hair Cells.

The ideal treatment for sensory hearing loss is to regenerate inner ear hair cells (HCs) through stem cell therapy, thereby restoring the function and structure of the cochlea. Previous studies have found that Lgr5+ supporting cells (SCs) in the inner ear can regenerate HCs, thus being considered inner ear progenitor cells. In addition to traditional biochemical factors, physical factors such as electrical conductivity also play a crucial role in the regulation of stem cell proliferation and differentiation. In this study, the graphene substrates were used to culture Lgr5+ progenitor cells and investigated their regulatory effects on cells. It was demonstrated that the graphene substrates displayed great cytocompatibility for Lgr5+ progenitors and promoted their sphere-forming ability. Moreover, more Myosin7a+ cells were found on the graphene substrates compared with tissue culture polystyrene (TCPS). These results suggest that graphene is an efficient interface that can promote the differentiation of Lgr5+ progenitors into HCs, which is great significance for its future application in combination with Lgr5+ cells to regenerate HCs in the inner ear.

[Functional MRI in normal subjects and sudden unilateral sensorineural hearing loss patients].

OBJECTIVE: Brain activities in responses to amplitude modulation (AM) was evaluated using functional MRI (fMRI) in subjects with sudden unilateral sensorineural hearing loss (SSNHL) and those with normal hearing (NH). METHODS: Totally 25 subjects with normal hearing and 30 with SSNHL were examined with fMRI in response to AM tones of 500, 2000 and 4000 Hz respectively with the modulation frequency at 8 Hz. The fMRI was examined within 12 days after the onset of SSNHL. The AM signals were presented at 96 dB SPL binaurally. An event-related design was combined with a sparse clustered volume acquisitioning paradigm in data collection in the attempt to reduce the influence of acoustic scanner noise. SPM2 software was used for offline data analyzing. RESULTS: Brain activation in fMRI image was found mainly in the primary auditory cortex (PAC) in both subjects with NH and SSNHL NH subjects showed a clear lateralization to left cerebral hemisphere(11/16) and SSNHL patients showed a lateralization ipsilateral to the impaired ear(16/22). The activation voxel and intensity shown in BOLD were found to be decreased with increasing signal frequency in both groups. CONCLUSION: The difference in the lateralization between the two groups suggests that an adaptive process occurs shortly after the onset of SSNHL

Resection of recurrent third branchial cleft fistulas assisted by flexible pharyngotomy.

BACKGROUND: Treatment of fistulas arising from the third branchial cleft includes endoscopic cauterization or open cervical fistulectomy. Both approaches are associated with recurrence rates of 14%-18%, and possibly greater rates when the fistula has been treated operatively beforehand. Treatment of fistulas arising from the third branchial cleft is associated with an inordinate recurrence rate. Recurrence may be multifactorial and related to incomplete resection of all of the anatomical elements of the fistula. AIM: To present a new approach that involves complete resection of the recurrent fistula by a combined therapeutic approach. METHODS: Here, 12 adult patients diagnosed with recurrent third branchial cleft fistulas underwent a combined therapy assisted by flexible fiber-optic pharyngoscopy to identify and resect the entry site of the fistula into the pyriform sinus. The fistulous opening into the pyriform sinus was identified by flexible fiber-optic pharyngoscopy. The application of intubation with a guidewire by pharyngoscopy, in addition to the removal of the partial excision of the thyroid cartilage, allowed complete resection of the opening and all parts of the fistula tract. RESULTS: All of the internal openings of the fistulas in the pharynx were found and easily identified by flexible fiber-optic pharyngoscopy. All of the 12 patients underwent complete resection of the recurrent fistula by the combined therapeutic approach. There were no postoperative complications such as parapharyngeal abscess or wound infection, injury or dysfunction of the recurrent laryngeal or superior laryngeal nerves. The pharyngeal edema had degraded, and the pharyngeal wound healed postoperatively within 1 wk. Laryngeal endoscopy and voice analysis were performed on the 14th d post-operatively. Vocal cord movements did not change. The characters of voice for jitter, shimmer, and normalized noise energy were all within normal limits. In addition, no recurrences were observed during the 13-60 mo follow-up period. CONCLUSION: It can be concluded that the proposed combined therapy is associated with excellent results, minimal morbidity, and no recurrence.

DUAL-GLOW: Conditional Flow-Based Generative Model for Modality Transfer.

Positron emission tomography (PET) imaging is an imaging modality for diagnosing a number of neurological diseases. In contrast to Magnetic Resonance Imaging (MRI), PET is costly and involves injecting a radioactive substance into the patient. Motivated by developments in modality transfer in vision, we study the generation of certain types of PET images from MRI data. We derive new flow-based generative models which we show perform well in this small sample size regime (much smaller than dataset sizes available in standard vision tasks). Our formulation, DUAL-GLOW, is based on two invertible networks and a relation network that maps the latent spaces to each other. We discuss how given the prior distribution, learning the conditional distribution of PET given the MRI image reduces to obtaining the conditional distribution between the two latent codes w.r.t. the two image types. We also extend our framework to leverage "side" information (or attributes) when available. By controlling the PET generation through "conditioning" on age, our model is also able to capture brain FDG-PET (hypometabolism) changes, as a function of age. We present experiments on the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset with 826 subjects, and obtain good performance in PET image synthesis, qualitatively and quantitatively better than recent works.

Small-world properties of the whole-brain functional networks in patients with obstructive sleep apnea-hypopnea syndrome.

OBJECTIVE: To explore the small-world properties of brain functional networks in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) to aid diagnosis. METHODS: A total of 29 OSAHS patients and 26 matched healthy volunteers were scanned with blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) separately, and the whole brain was divided into 90 districts via automated anatomical labeling. The matrix Z was then built through a Fisher Z transformation. Two-sample t tests were applied to evaluate the changes in small-world properties in OSAHS patients compared to the control group. The properties included Eglobal, Elocal, and small-world parameters Lp, Cp, γ, λ, and σ. RESULTS: Both groups satisfied the small-world properties (σ > 1) within the sparsity range of 0.1-0.2. However, compared with the control group, the OSAHS group performed significantly lower in Cp, Elocal, and Eglobal (p < 0.05) and higher in Lp (p < 0.05). The γ, σ, and λ values were not significantly different between the two groups. CONCLUSION: Both healthy and OSAHS patients exhibited small-world properties in functional networks, but a subset of these small-world properties in OSAHS patients performed differently. These changes will not only provide a new perspective for pathophysiological mechanisms of OSAHS but will also help in understanding the disease in terms of whole-brain functional networks.

[Dominant hemisphere and tonotopic organization of auditory functional MRI in Chinese].

OBJECTIVE: Functional MRI (fMRI) was measured in responses to stimulations of different frequencies to investigate dominant hemisphere and tonotopic organization in primary and secondary auditory cortex. METHODS: 25 healthy subjects with normal hearing were examined using tones of 0.5, 2 or 4 kHz that were amplitude modulated (AM) sinusoidally at 8 Hz. The AM signals were presented at 96 dB SPL Event-related design was combined with a sparse clustered volume acquisitioning paradigm for data collection in the attempt to reduce the influence of acoustic scanner noise. SPM2 software was used for offline data analyzing. RESULTS: Data from 9 subjects were discarded due to a large head movement during recording. In the rest of 16 subjects, activation was found mainly in the primary auditory cortex. In most of these cases, the activation area and intensity by BOLD were find to be decreased with increasing signal frequency. In a great portion of cases (6 left and 7 right hemispheres), a lateral-medial preference for low-to-high frequency response shift was clearly demonstrated in the primary auditory cortex. However, this was not clear in all other cases. No significant rule could be found in secondary auditory cortex activation. CONCLUSION: The responses to AM signals showed a clear lateralization to left cerebral hemisphere. The activated area and response intensity decreased with increasing frequency of stimulation. The activation is related to the signal frequency with high frequency AM activating more medially.

Aberrant Interhemispheric Connectivity in Obstructive Sleep Apnea-Hypopnea Syndrome.

OBJECTIVE: To determine the changes in interhemispheric functional coordination in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) relative to controls, using a recently introduced method of analysis: voxel-mirrored homotopic connectivity (VMHC). METHODS: Twenty-nine patients with OSAHS and twenty-six normal sex-, age-, and education-matched controls were recruited and resting-state functional magnetic resonance imaging data were obtained. We employed VMHC to analyze the interhemispheric functional connectivity differences between groups. The z-values of alterations in VMHC in brain region were correlated with clinical characteristics. RESULTS: Compared with controls, patients with OSAHS had significantly higher scores for body mass index (t = 5.749, P < 0.001), apnea-hypopnea index (AHI; t = 7.706, P < 0.001), oxygen desaturation index (t = 6.041, P < 0.001), and Epworth sleepiness scale (t = 3.711, P < 0.001), but significantly lower scores on the Rey-Osterrieth complex figure test-immediate recall (t = -3.727, P < 0.05). On the same basis, the VMHC showed significant increases in bilateral calcarine cortex and precuneus. Moreover, significant, positive correlations were found in only these areas between the AHI and the VMHC change coefficients (r = 0.399, P = 0.032; r = 0.378, P = 0.043). CONCLUSION: We found a memory defect in patients with OSAHS. The correlation between the abnormal VMHC and the AHI in patients with OSAHS suggested that AHI might be a key factor in cognitive dysfunction, which might offer new insights into the neural pathophysiology underlying OSAHS-related cognitive deficits.