It has been recently shown that if an input-affine nonlinear MIMO system is uniformly invertible and its normal form has a special structure, it is possible to design feedback laws that solve ...relevant design problems via dynamic output feedback, such as asymptotic stabilization and/or robust almost feedback linearization. The purpose of this note is to shed some light into the issue of existence of normal forms having such special structure and, in particular, to show that this is actually a consequence of a stronger property of invertibility, introduced by Hirschorn in the late 1970s.
The nuclear receptor peroxisome proliferator-activated receptor-δ/β (PPAR-d) is upregulated in human colorectal cancers, but its role in colonic tumorigenesis remains controversial.
We generated a ...novel mouse model of intestinally targeted PPAR-d overexpression to simulate PPAR-d upregulation in human colon carcinogenesis. Colon-specific PPAR-d overexpression was confirmed by real-time reverse transcription polymerase chain reaction, immunoblotting, and activity assays. Mice with and without targeted PPAR-d overexpression were tested for azoxymethane (AOM)-induced colonic tumorigenesis. Mouse whole-genome transcriptome microarray analyses were performed to identify PPAR-d target genes to promote tumorigenesis. We used linear models to test for PPAR-d overexpression trend effects on tumor multiplicity. All statistical tests were two-sided.
Targeted PPAR-d overexpression markedly increased colonic tumor incidence (from 0 of 10 wild-type WT littermate mice to 9 of 10 mice P < .001 in 2 FVB/N background mouse lines villin-PPAR-d-1 and villin-PPAR-d-2 at a 5-mg/kg AOM dose) and multiplicity (number of tumors per mouse per mg/kg dose of AOM increased from 0.47 95% confidence interval CI = 0.22 to 0.72 for the WT littermates to 2.15 95% CI = 1.90 to 2.40 P < .001 for the villin-PPAR-d-1 mice and from 0.44 95% CI = 0.09 to 0.79 for the WT littermates to 1.91 95% CI = 1.57 to 2.25 P < .001 for the villin-PPAR-d-2 mice). PPAR-d overexpression reversed resistance to AOM-induced colonic tumorigenesis in C57BL/6 mice. PPAR-d overexpression modulated expression of several novel PPAR-d target genes in normal-appearing colonic epithelial cells of mice with PPAR-d overexpression in a pattern that matched the changes in colonic tumors.
Our finding that PPAR-d upregulation profoundly enhances susceptibility to colonic tumorigenesis should impact the development of strategies of molecularly targeting PPAR-d in cancer and noncancerous diseases.
This study aimed to investigate abnormal static and dynamic functional network connectivity (FNC) and its association with cognitive function in patients with presbycusis.
In total, 60 patients with ...presbycusis and 60 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) and cognitive assessments. Group independent component analysis (ICA) was carried out on the rs-fMRI data, and eight resting-state networks (RSNs) were identified. Static and dynamic FNCs (sFNC and dFNC) were then constructed to evaluate differences in RSN connectivity between the patients with presbycusis and the HCs. Furthermore, the correlations between these differences and cognitive scores were analyzed.
Patients with presbycusis had differences in sFNC compared with HCs, mainly reflected in decreased sFNC in the default mode network (DMN)-left frontoparietal network (LFPN) and attention network (AN)-cerebellum network (CN) pairs, but they had increased sFNC in the auditory network (AUN) between DMN domains. The decreased sFNC in the DMN-LFPN pair was negatively correlated with their TMT-B score (
= -0.441,
= 0.002). Patients with presbycusis exhibited aberrant dFNCs in State 2 and decreased dFNCs between the CN and AN and the visual network (VN). Moreover, the presbycusis group had a shorter mean dwell time (MDT) and fraction time (FT) in State 3 (
= 0.0027;
= 0.0031, respectively).
This study highlighted differences in static and dynamic functional connectivity in patients with presbycusis and suggested that FNC may serve as an important biomarker of cognitive performance since abnormal alterations can better track cognitive impairment in presbycusis.
This article provides a detailed comparative analysis of five orientational, two degrees of freedom (DOF) mechanisms whose envisioned application is the wrist of the iCub humanoid robot. Firstly, the ...current iCub mk.2 wrist implementation is presented, and the desired design objectives are proposed. Prominent architectures from literature such as the spherical five-bar linkage and spherical six-bar linkage, the OmniWrist-III and the Quaternion joint mechanisms are modeled and analyzed for the said application. Finally, a detailed comparison of their workspace features is presented. The Quaternion joint mechanism emerges as a promising candidate from this study.
To investigate resting-state connectivity and further understand directional aspects of implicit alterations in presbycusis patients, we used degree centrality (DC) and Granger causality analysis ...(GCA) to detect functional hubs of the whole-brain network and then analyze directional connectivity. Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 40 presbycusis patients and 40 healthy controls matched for age, gender, and education. We used DC analysis and GCA to characterize abnormal brain networks in presbycusis patients. The associations of network centrality and directed functional connectivity (FC) with clinical measures of presbycusis were also examined according to the above results. We found that the network centrality of left frontal middle gyrus (MFG) was significantly lower than that of healthy control group. Unidirectionally, the left MFG revealed increased directional connectivity to the left superior frontal gyrus (SFG), while the left MFG exhibited decreased directional connectivity to the left middle temporal gyrus (MTG) and right lingual gyrus (LinG). And the decreased directional connectivity was found from the left precentral gyrus (PrCG) to the left MFG. In addition, the Trail-Making Test B (TMT-B) score was negatively correlated with the decreased DC of the left MFG (r = −0.359,
p
= 0.032). Resting-state fMRI provides a novel method for identifying aberrant brain network architecture. These results primarily indicate altered functional hubs and abnormal frontal lobe connectivity patterns that may further reflect executive dysfunction in patients with presbycusis.
The phantom sound of tinnitus is considered to be associated with abnormal functional coupling between the nucleus accumbens (NAc) and the prefrontal cortex, which may form a frontostriatal top-down ...gating system to evaluate and modulate sensory signals. Resting-state functional magnetic resonance imaging (fMRI) was used to recognize the aberrant directional connectivity of the NAc in chronic tinnitus and to ascertain the relationship between this connectivity and tinnitus characteristics.
Participants included chronic tinnitus patients (
= 50) and healthy controls (
= 55), matched for age, sex, education, and hearing thresholds. The hearing status of both groups was comparable. On the basis of the NAc as a seed region, a Granger causality analysis (GCA) study was conducted to investigate the directional connectivity and the relationship with tinnitus duration or distress.
Compared with healthy controls, tinnitus patients exhibited abnormal directional connectivity between the NAc and the prefrontal cortex, principally the middle frontal gyrus (MFG), orbitofrontal cortex (OFC), and inferior frontal gyrus (IFG). Additionally, positive correlations between tinnitus handicap questionnaire (THQ) scores and increased directional connectivity from the right NAc to the left MFG (
= 0.357,
= 0.015) and from the right MFG to the left NAc (
= 0.626,
< 0.001) were observed. Furthermore, the enhanced directional connectivity from the right NAc to the right OFC was positively associated with the duration of tinnitus (
= 0.599,
< 0.001).
In concurrence with expectations, tinnitus distress was correlated with enhanced directional connectivity between the NAc and the prefrontal cortex. The current study not only helps illuminate the neural basis of the frontostriatal gating control of tinnitus sensation but also contributes to deciphering the neuropathological features of tinnitus.
Sudden sensorineural hearing loss (SSNHL) is a common otology emergency and some SSNHL will develop into a long-term hearing loss (LSNHL). However, whether SSNHL and LSNHL have similar psychiatric ...patterns remains unknown, as well as the neural substrates. Increasing evidence has proved that the cerebellar network plays a vital role in hearing, cognition processing, and emotion control. Thus, we recruited 20 right SSNHL (RSSNHL), 20 right LSNHL (RLSNHL), and 24 well-matched healthy controls to explore the cerebellar patterns among the three groups. Every participant underwent pure tone audiometry tests, neuropsychological evaluations, and MRI scanning. Independent component analysis (ICA) was carried out on the MRI data and the cerebellar network was extracted. Granger causality analysis (GCA) was conducted using the significant cerebellar region as a seed. Pearson’s correlation analysis was computed between imaging characteristics and clinical features. ICA found the effect of group on right cerebellum lobule V for the cerebellar network. Then, we found decreased outflow from right cerebellum lobule V to right middle orbitofrontal cortex, inferior frontal gyrus, anterior cingulate cortex, superior temporal gyrus, and dorsal lateral prefrontal cortex in RSSNHL group in GCA analysis. No significance was found in RLSNHL subjects. Additionally, the RSSNHL group showed increased effective connectivity from the right middle frontal gyrus (MFG) and the RLSNHL group showed increased effective connectivity from the right insula and temporal pole to the right cerebellum lobule V. Moreover, connections between right cerebellum lobule V and mean time series of the cerebellar network was negatively correlated with anxiety score in RSSNHL and negatively correlated with depression scores in RLSNHL. Effective connectivity from right MFG to right cerebellum lobule V could predict anxiety status in RSSNHL subjects. Our results may prove potential imaging biomarkers and treatment targets for hearing loss in future work.
Purpose:
Tinnitus is along with tension-type headache that will influence the cerebral blood flow (CBF) and accelerate the tinnitus severity. However, the potential associations between tension-type ...headache and tinnitus is still unknown. The current study will explore whether abnormal CBF exists in tinnitus patients and examine the effects of headache on CBF in tinnitus patients.
Materials and Methods:
Resting-state perfusion magnetic resonance imaging was performed in 40 chronic tinnitus patients and 50 healthy controls using pseudocontinuous arterial spin labeling. Regions with CBF differences between tinnitus patients and healthy controls were investigated. The effects of headache on tinnitus for CBF changes were further explored. Correlation analyses revealed the relationship between CBF values and tinnitus distress as well as CBF values and headache degree.
Results:
Relative to healthy controls, chronic tinnitus showed decreased CBF, mainly in right superior temporal gyrus (STG), left middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); the CBF in the right STG and the left MFG was negatively correlated with THQ scores (
r
= −0.553,
p
= 0.001;
r
= −0.399,
p
= 0.017). We also observed a significant effect of headache on tinnitus for CBF in the right STG. Furthermore, the headache degree was correlated positively with tinnitus distress (
r
= 0.594,
p
= 0.020).
Conclusion:
Decreased CBF in auditory and prefrontal cortex was observed in chronic tinnitus patients. Headache may accelerate CBF reductions in tinnitus, which may form the basis for the neurological mechanism in chronic tinnitus with tension-type headache.
Purpose
The possible relationship between migraine and tinnitus still remains elusive although migraine is often accompanied by chronic tinnitus. Several neuroimaging studies have reinforced the ...cognitive network abnormality in migraine and probably as well as tinnitus. The present work aims to investigate the dynamic neurocognitive network alterations of migraine comorbid with tinnitus.
Materials and Methods
Participants included migraine patients (
n
= 32), tinnitus patients (
n
= 20), migraine with tinnitus (
n
= 27), and healthy controls (
n
= 47), matched for age and gender. Resting-state functional magnetic resonance imaging (rs-fMRI) with independent component analysis (ICA), sliding window cross-correlation, and clustering state analysis was used to detect the dynamic functional network connectivity (dFNC) of each group. Correlation analyses illustrated the association between clinical symptoms and abnormal dFNC in migraine as well as tinnitus.
Results
Compared with healthy controls, migraine patients exhibited decreased cerebellar network and visual network (CN-VN) connectivity in State 2; migraine with tinnitus patients showed not only decreased CN-VN connectivity in State 2 but also decreased cerebellar network and executive control network (CN-ECN) connectivity in State 2 and increased cerebellar network and somatomotor network (SMN-VN) connectivity in State 1. The abnormal cerebellum dFNC with the executive control network (CN-ECN) was negatively correlated with headache frequency of migraine (rho = −0.776,
p
= 0.005).
Conclusion
Brain network characteristics of migraine with tinnitus patients may indicate different mechanisms for migraine and tinnitus. Our results demonstrated a transient pathologic state with atypical cerebellar-cortical connectivity in migraine with tinnitus patients, which might be used to identify the neuro-pathophysiological mechanisms in migraine accompanied by tinnitus.
Presbycusis is characterized by bilateral sensorineural hearing loss at high frequencies and is often accompanied by cognitive decline. This study aimed to identify the topological reorganization of ...brain functional network in presbycusis with/without cognitive decline by using graph theory analysis approaches based on resting-state functional magnetic resonance imaging (rs-fMRI).
Resting-state fMRI scans were obtained from 30 presbycusis patients with cognitive decline, 30 presbycusis patients without cognitive decline, and 50 age-, sex-, and education-matched healthy controls. Graph theory was applied to analyze the topological properties of brain functional networks including global and nodal metrics, modularity, and rich-club organization.
At the global level, the brain functional networks of all participants were found to possess small-world properties. Also, significant group differences in global network metrics were observed among the three groups such as clustering coefficient, characteristic path length, normalized characteristic path length, and small-worldness. At the nodal level, several nodes with abnormal betweenness centrality, degree centrality, nodal efficiency, and nodal local efficiency were detected in presbycusis patients with/without cognitive decline. Changes in intra-modular connections in frontal lobe module and inter-modular connections in prefrontal subcortical lobe module were found in presbycusis patients exposed to modularity analysis. Rich-club nodes were reorganized in presbycusis patients, while the connections among them had no significant group differences.
Presbycusis patients exhibited topological reorganization of the whole-brain functional network, and presbycusis patients with cognitive decline showed more obvious changes in these topological properties than those without cognitive decline. Abnormal changes of these properties in presbycusis patients may compensate for cognitive impairment by mobilizing additional neural resources.
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