Disruption of effective connectivity from the dorsolateral prefrontal cortex to the orbitofrontal cortex by negative emotional distraction in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive-affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients. METHOD: A total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging. RESULTS: During the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p < 0.05, Bonferroni-corrected). CONCLUSIONS: Exaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.

Cognitive functioning in obsessive-compulsive disorder: a meta-analysis.

BACKGROUND: Substantial empirical evidence has indicated impairment in the cognitive functioning of patients with obsessive-compulsive disorder (OCD) despite inconsistencies. Although several confounding factors have been investigated to explain the conflicting results, the findings remain mixed. This study aimed to investigate cognitive dysfunction in patients with OCD using a meta-analytic approach. METHOD: The PubMed database was searched between 1980 and October 2012, and reference lists of review papers were examined. A total of 221 studies were identified, of which 88 studies met inclusion criteria. Neuropsychological performance and demographic and clinical variables were extracted from each study. RESULTS: Patients with OCD were significantly impaired in tasks that measured visuospatial memory, executive function, verbal memory and verbal fluency, whereas auditory attention was preserved in these individuals. The largest effect size was found in the ability to recall complex visual stimuli. Overall effect estimates were in the small to medium ranges for executive function, verbal memory and verbal fluency. The effects of potentially confounding factors including educational level, symptom severity, medication status and co-morbid disorders were not significant. CONCLUSIONS: Patients with OCD appear to have wide-ranging cognitive deficits, although their impairment is not so large in general. The different test forms and methods of testing may have influenced the performance of patients with OCD, indicating the need to select carefully the test forms and methods of testing used in future research. The effects of various confounding variables on cognitive functioning need to be investigated further and to be controlled before a definite conclusion can be made.

Volumetric Measurement of Relative CBV Using T1-Perfusion-Weighted MRI with High Temporal Resolution Compared with Traditional T2*-Perfusion-Weighted MRI in Postoperative Patients with High-Grade Gliomas.

BACKGROUND AND PURPOSE: T1-PWI with high temporal resolution may provide a reliable relative CBV value as a valid alternative to T2*-PWI under increased susceptibility. The purpose of this study was to assess the technical and clinical performance of T1-relative CBV in patients with postoperative high-grade gliomas. MATERIALS AND METHODS: Forty-five MRIs of 34 patients with proved high-grade gliomas were included. In all MRIs, T1- and T2*-PWIs were both acquired and processed semiautomatically to generate relative CBV maps using a released commercial software. Lesion masks were overlaid on the relative CBV maps, followed by a histogram of the whole VOI. The intraclass correlation coefficient and Bland-Altman plots were used for quantitative and qualitative comparisons. Signal loss from both methods was compared using the Wilcoxon signed-rank test of zero voxel percentage. The MRIs were divided into a progression group (n = 20) and a nonprogression group (n = 14) for receiver operating characteristic curve analysis. RESULTS: Fair intertechnique consistency was observed between the 90th percentiles of the T1- and T2*-relative CBV values (intraclass correlation coefficient = 0.558, P < .001). T2*-PWI revealed a significantly higher percentage of near-zero voxels than T1-PWI (17.7% versus 3.1%, P < .001). There was no statistically significant difference between the area under the curve of T1- and T2*-relative CBV (0.811 versus 0.793, P = .835). T1-relative CBV showed 100% sensitivity and 57.1% specificity for the detection of progressive lesions. CONCLUSIONS: T1-relative CBV demonstrated exquisite diagnostic performance for detecting progressive lesions in postoperative patients with high-grade gliomas, suggesting the potential role of T1-PWI as a valid alternative to the traditional T2*-PWI.

Ion-pair reorganization regulates reactivity in photoredox catalysts.

Cyclometalated and polypyridyl complexes of d6 metals are promising photoredox catalysts, using light to drive reactions with high kinetic or thermodynamic barriers via the generation of reactive radical intermediates. However, while tuning of their redox potentials, absorption energy, excited-state lifetime and quantum yield are well-known criteria for modifying activity, other factors could be important. Here we show that dynamic ion-pair reorganization controls the reactivity of a photoredox catalyst, [Ir[dF(CF3)ppy]2(dtbpy)]X. Time-resolved dielectric-loss experiments show how counter-ion identity influences excited-state charge distribution, evincing large differences in both the ground- and excited-state dipole moment depending on whether X is a small associating anion (PF6-) that forms a contact-ion pair versus a large one that either dissociates or forms a solvent-separated pair (BArF4-). These differences correlate with the reactivity of the photocatalyst toward both reductive and oxidative electron transfer, amounting to a 4-fold change in selectivity toward oxidation versus reduction. These results suggest that ion pairing could be an underappreciated factor that modulates reactivity in ionic photoredox catalysts.

Intraindividual Comparison between the Contrast-Enhanced Golden-Angle Radial Sparse Parallel Sequence and the Conventional Fat-Suppressed Contrast-Enhanced T1-Weighted Spin-Echo Sequence for Head and Neck MRI.

BACKGROUND AND PURPOSE: The golden-angle radial sparse parallel-volumetric interpolated breath-hold (GRASP-VIBE) sequence is a recently introduced imaging technique with high resolution. This study compared the image quality between conventional fat-suppressed T1-weighted TSE and GRASP-VIBE after gadolinium enhancement in the head and neck region. MATERIALS AND METHODS: Data from 65 patients with clinical indications for head and neck MR imaging between September 2020 and January 2021 were retrospectively reviewed. Two radiologists assessed the overall image quality, overall artifacts, and image conspicuities in the oropharynx, hypopharynx, and cervical lymph nodes according to 5-point scores (best score: 5). Interobserver agreement was assessed using weighted κ statistics. The SNR and contrast-to-noise ratio were calculated and compared between the 2 sequences using a paired Wilcoxon signed rank test. RESULTS: The analysis included 52 patients (mean age, 60 [SD, 14 ] years; male, 71.2% [37/52]) who were mostly diagnosed with head and neck malignancies (94.3% [50/52]). κ statistics ranged from slight agreement in cervical lymph node conspicuity (κ = 0.18) to substantial agreement in oropharyngeal mucosal conspicuity (κ = 0.80) (κ range, 0.18-0.80). Moreover, GRASP-VIBE demonstrated significantly higher mean scores in overall image quality (4.68 [SD, 0.41] versus 3.66 [SD, 0.73]), artifacts (4.47 [SD, 0.48] versus 3.58 [SD, 0.71]), oropharyngeal mucosal conspicuity (4.85 [SD, 0.41] versus 4.11 [SD, 0.79]), hypopharyngeal mucosal conspicuity (4.84 [SD, 0.34] versus 3.58 [SD, 0.81]), and cervical lymph node conspicuity (4.79 [SD, 0.32] versus 4.08 [SD, 0.64]) than fat-suppressed T1-weighted TSE (all, P < .001). Furthermore, GRASP-VIBE demonstrated a higher SNR (22.8 [SD, 11.5] versus 11.3 [SD, 5.6], P < .001) and contrast-to-noise ratio (4.7 [SD, 5.4] versus 2.3 [SD, 2.7], P = .059) than fat-suppressed T1-weighted TSE. CONCLUSIONS: GRASP-VIBE provided better image quality with fewer artifacts than conventional fat-suppressed T1-weighted TSE for the head and neck regions.

Prediction of Human Papillomavirus Status and Overall Survival in Patients with Untreated Oropharyngeal Squamous Cell Carcinoma: Development and Validation of CT-Based Radiomics.

BACKGROUND AND PURPOSE: Human papillomavirus is a prognostic marker for oropharyngeal squamous cell carcinoma. We aimed to determine the value of CT-based radiomics for predicting the human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Eighty-six patients with oropharyngeal squamous cell carcinoma were retrospectively collected and grouped into training (n = 61) and test (n = 25) sets. For human papillomavirus status and overall survival prediction, radiomics features were selected via a random forest-based algorithm and Cox regression analysis, respectively. Relevant features were used to build multivariate Cox regression models and calculate the radiomics score. Human papillomavirus status and overall survival prediction were assessed via the area under the curve and concordance index, respectively. The models were validated in the test and The Cancer Imaging Archive cohorts (n = 78). RESULTS: For prediction of human papillomavirus status, radiomics features yielded areas under the curve of 0.865, 0.747, and 0.834 in the training, test, and validation sets, respectively. In the univariate Cox regression, the human papillomavirus status (positive: hazard ratio, 0.257; 95% CI, 0.09-0.7; P = .008), T-stage (≥III: hazard ratio, 3.66; 95% CI, 1.34-9.99; P = .011), and radiomics score (high-risk: hazard ratio, 3.72; 95% CI, 1.21-11.46; P = .022) were associated with overall survival. The addition of the radiomics score to the clinical Cox model increased the concordance index from 0.702 to 0.733 (P = .01). Validation yielded concordance indices of 0.866 and 0.720. CONCLUSIONS: CT-based radiomics may be useful in predicting human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma.

Image Quality of Low-Dose Cerebral Angiography and Effectiveness of Clinical Implementation on Diagnostic and Neurointerventional Procedures for Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Awareness of the potential for exposure to high doses of radiation from interventional radiologic procedures has increased. The purpose of this study was to evaluate image quality and dose reduction of low-dose cerebral angiography during diagnostic and therapeutic procedures for intracranial aneurysms. MATERIALS AND METHODS: A retrospective review of 1137 prospectively collected patients between January 2012 and June 2014 was performed. Beginning in April 2013, a dose-reduction strategy was implemented. Subjective image-quality assessment of 506 standard and 540 low-dose cerebral angiography images was performed by 2 neuroradiologists using a 5-point scale and was tested using noninferiority statistics. Radiation dose-area product and air kerma of 1046 diagnostic and 317 therapeutic procedures for intracranial aneurysms were analyzed and compared between groups before (group 1) and after (group 2) clinical implementation of a dose-reduction strategy. RESULTS: The image quality of the low-dose cerebral angiography was not inferior on the basis of results from the 2 readers. For diagnostic cerebral angiography, the mean dose-area product and air kerma were 140.8 Gy×cm2 and 1.0 Gy, respectively, in group 1 and 82.0 Gy×cm2 and 0.6 Gy in group 2 (P < .001, P < .001). For the neurointerventional procedure, the mean dose-area product and air kerma were 246.0 Gy×cm2 and 3.7 Gy, respectively, in group 1 and 169.8 Gy×cm2 and 3.3 Gy in group 2 (P < .001, P = .291). CONCLUSIONS: With low-dose cerebral angiography, image quality was maintained, and implementation of dose-reduction strategies reduced radiation doses in patients undergoing diagnostic and neurointerventional procedures for intracranial aneurysms.

Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src.

Tyrosine phosphorylation of CAS (Crk-associated substrate, p130(Cas)) has been implicated as a key signaling step in integrin control of normal cellular behaviors, including motility, proliferation, and survival. Aberrant CAS tyrosine phosphorylation may contribute to cell transformation by certain oncoproteins, including v-Crk and v-Src, and to tumor growth and metastasis. The CAS substrate domain (SD) contains 15 Tyr-X-X-Pro motifs, which are thought to represent the major tyrosine phosphorylation sites and to function by recruiting downstream signaling effectors, including c-Crk and Nck. CAS makes multiple interactions, direct and indirect, with the tyrosine kinases Src and focal adhesion kinase (FAK), and as a result of this complexity, several plausible models have been proposed for the mechanism of CAS-SD phosphorylation. The objective of this study was to provide experimental tests of these models in order to determine the most likely mechanism(s) of CAS-SD tyrosine phosphorylation by FAK and Src. In vitro kinase assays indicated that FAK has a very poor capacity to phosphorylate CAS-SD, relative to Src. However, FAK expression along with Src was found to be important for achieving high levels of CAS tyrosine phosphorylation in COS-7 cells, as well as recovery of CAS-associated Src activity toward the SD. Structure-functional studies for both FAK and CAS further indicated that FAK plays a major role in regulating CAS-SD phosphorylation by acting as a docking or scaffolding protein to recruit Src to phosphorylate CAS, while a secondary FAK-independent mechanism involves Src directly bound to the CAS Src-binding domain (SBD). Our results do not support models in which FAK either phosphorylates CAS-SD directly or phosphorylates CAS-SBD to promote Src binding to this site.

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

BACKGROUND AND PURPOSE: The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. MATERIALS AND METHODS: Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (<1 year, n = 16) and longer (≥1 year, n = 43) durations of parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. RESULTS: The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P < .05). The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P < .05). The group with longer duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right posterior cingulate was used as a seed, and in the parieto-occipital areas when the left or right caudate was used as a seed (corrected P < .05). No differences in cortical thickness were found in all group contrasts. CONCLUSIONS: Resting-state functional connectivity and WM alterations might be useful imaging biomarkers for identifying changes in patients with Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. The functional and microstructural substrates may topographically differ depending on the rate of cognitive decline in these patients.

Effects of agmatine on blood-brain barrier stabilization assessed by permeability MRI in a rat model of transient cerebral ischemia.

BACKGROUND AND PURPOSE: BBB disruption after acute ischemic stroke and subsequent permeability increase may be enhanced by reperfusion. Agmatine has been reported to attenuate BBB disruption. Our aim was to evaluate the effects of agmatine on BBB stabilization in a rat model of transient cerebral ischemia by using permeability dynamic contrast-enhanced MR imaging at early stages and subsequently to demonstrate the feasibility of dynamic contrast-enhanced MR imaging for the investigation of new therapies. MATERIALS AND METHODS: Thirty-four male Sprague-Dawley rats were subjected to transient MCA occlusion for 90 minutes. Immediately after reperfusion, agmatine (100 mg/kg) or normal saline was injected intraperitoneally into the agmatine-treated group (n = 17) or the control group, respectively. MR imaging was performed after reperfusion. For quantitative analysis, regions of interest were defined within the infarct area, and values for volume transfer constant, rate transfer coefficient, volume fraction of extravascular extracellular space, and volume fraction of blood plasma were obtained. Infarct volume, infarct growth, quantitative imaging parameters, and numbers of factor VIII-positive cells after immunohistochemical staining were compared between control and agmatine-treated groups. RESULTS: Among the permeability parameters, volume transfer constant and volume fraction of extravascular extracellular space were significantly lower in the agmatine-treated group compared with the control group (0.05 ± 0.02 minutes(-1) versus 0.08 ± 0.03 minute(-1), P = .012, for volume transfer constant and 0.12 ± 0.06 versus 0.22 ± 0.15, P = .02 for volume fraction of extravascular extracellular space). Other permeability parameters were not significantly different between the groups. The number of factor VIII-positive cells was less in the agmatine-treated group than in the control group (3-fold versus 4-fold, P = .037). CONCLUSIONS: In ischemic stroke, agmatine protects the BBB, which can be monitored in vivo by quantification of permeability by using dynamic contrast-enhanced MR imaging. Therefore, dynamic contrast-enhanced MR imaging may serve as a potential imaging biomarker for assessing the BBB stabilization properties of pharmacologic agents.

Differentiation between Cystic Pituitary Adenomas and Rathke Cleft Cysts: A Diagnostic Model Using MRI.

BACKGROUND AND PURPOSE: Cystic pituitary adenomas may mimic Rathke cleft cysts when there is no solid enhancing component found on MR imaging, and preoperative differentiation may enable a more appropriate selection of treatment strategies. We investigated the diagnostic potential of MR imaging features to differentiate cystic pituitary adenomas from Rathke cleft cysts and to develop a diagnostic model. MATERIALS AND METHODS: This retrospective study included 54 patients with a cystic pituitary adenoma (40 women; mean age, 37.7 years) and 28 with a Rathke cleft cyst (18 women; mean age, 31.5 years) who underwent MR imaging followed by surgery. The following imaging features were assessed: the presence or absence of a fluid-fluid level, a hypointense rim on T2-weighted images, septation, an off-midline location, the presence or absence of an intracystic nodule, size change, and signal change. On the basis of the results of logistic regression analysis, a diagnostic tree model was developed to differentiate between cystic pituitary adenomas and Rathke cleft cysts. External validation was performed for an additional 16 patients with a cystic pituitary adenoma and 8 patients with a Rathke cleft cyst. RESULTS: The presence of a fluid-fluid level, a hypointense rim on T2-weighted images, septation, and an off-midline location were more common with pituitary adenomas, whereas the presence of an intracystic nodule was more common with Rathke cleft cysts. Multiple logistic regression analysis showed that cystic pituitary adenomas and Rathke cleft cysts can be distinguished on the basis of the presence of a fluid-fluid level, septation, an off-midline location, and the presence of an intracystic nodule (P = .006, .032, .001, and .023, respectively). Among 24 patients in the external validation population, 22 were classified correctly on the basis of the diagnostic tree model used in this study. CONCLUSIONS: A systematic approach using this diagnostic tree model can be helpful in distinguishing cystic pituitary adenomas from Rathke cleft cysts.

Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B.

The Nck family of Src homology (SH) 2/SH3 domain adaptors functions to link tyrosine phosphorylation induced by extracellular signals with downstream regulators of actin dynamics. We investigated the role of mammalian Nck adaptors in signaling from the activated platelet-derived growth factor (PDGF) receptor (PDGFbetaR) to the actin cytoskeleton. We report here that Nck adaptors are required for cytoskeletal reorganization and chemotaxis stimulated by PDGF-B. Analysis of tyrosine-phosphorylated proteins demonstrated that Crk-associated substrate (p130(Cas)), not the activated PDGFbetaR itself, is the major Nck SH2 domain-binding protein in PDGF-B-stimulated cells. Both Nck- and p130(Cas)-deficient cells fail to display cytoskeletal rearrangements, including the formation of membrane ruffles and the disassembly of actin bundles, typically shown by their WT counterparts in response to PDGF-B. Furthermore, Nck and p130(Cas) colocalize in phosphotyrosine-enriched membrane ruffles induced by PDGF-B in NIH 3T3 cells. These results suggest that Nck adaptors play an essential role in linking the activated PDGFbetaR with actin dynamics through a pathway that involves p130(Cas).

NF-kappaB-dependent expression of nitric oxide synthase is required for membrane fusion of chick embryonic myoblasts.

The activity of nitric oxide synthase (NOS) has recently been shown to increase transiently but dramatically in chick embryonic myoblasts that are competent for fusion and that NO acts as a messenger for the cell fusion. Here we show that the rise in NOS activity is tightly correlated with an increase in NOS protein level, and its synthesis is under transcriptional control. In addition, a partial cDNA sequence of NOS obtained by reverse transcription PCR on total RNA from chick myoblasts was found to be identical with that of the inducible type of NOS (iNOS) from chick macrophage. Thus chick myoblast NOS must belong to the family of iNOS. Consistently, pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappaB (NF-kappaB), prevented the expression of myoblast NOS. Furthermore the antioxidant also strongly inhibited cell fusion, and its inhibitory effect was reversed by treatment with sodium nitroprusside, an NO-generating agent. In addition, nuclear extracts obtained from myoblasts that were competent for fusion, but not those from proliferating cells or from fully differentiated myotubes, were capable of binding to the consensus NF-kappaB site in the promoter region of the gene encoding iNOS. These results suggest that NF-kappaB-dependent expression of NOS is an important step in membrane fusion of chick embryonic myoblasts.