Spatial selective attention is widely considered to be right hemisphere dominant. Previous functional magnetic resonance imaging studies, however, have reported bilateral ...blood-oxygenation-level-dependent responses in dorsal frontoparietal regions during anticipatory shifts of attention to a location (Kastner et al., 1999; Corbetta et al., 2000; Hopfinger et al., 2000). Right-lateralized activity has mainly been reported in ventral frontoparietal regions for shifts of attention to an unattended target stimulus (Arrington et al., 2000; Corbetta et al., 2000). However, clear conclusions cannot be drawn from these studies because hemispheric asymmetries were not assessed using direct voxelwise comparisons of activity in left and right hemispheres. Here, we used this technique to measure hemispheric asymmetries during shifts of spatial attention evoked by a peripheral cue stimulus and during target detection at the cued location. Stimulus-driven shifts of spatial attention in both visual fields evoked right-hemisphere dominant activity in temporoparietal junction (TPJ). Target detection at the attended location produced a more widespread right hemisphere dominance in frontal, parietal, and temporal cortex, including the TPJ region asymmetrically activated during shifts of spatial attention. However, hemispheric asymmetries were not observed during either shifts of attention or target detection in the dorsal frontoparietal regions (anterior precuneus, medial intraparietal sulcus, frontal eye fields) that showed the most robust activations for shifts of attention. Therefore, right hemisphere dominance during stimulus-driven shifts of spatial attention and target detection reflects asymmetries in cortical regions that are largely distinct from the dorsal frontoparietal network involved in the control of selective attention.
Objective
Focal brain lesions can have important remote effects on the function of distant brain regions. The resulting network dysfunction may contribute significantly to behavioral deficits ...observed after stroke. This study investigates the behavioral significance of changes in the coherence of spontaneous activity in distributed networks after stroke by measuring resting state functional connectivity (FC) using functional magnetic resonance imaging.
Methods
In acute stroke patients, we measured FC in a dorsal attention network and an arm somatomotor network, and determined the correlation of FC with performance obtained in a separate session on tests of attention and motor function. In particular, we compared the behavioral correlation with intrahemispheric FC to the behavioral correlation with interhemispheric FC.
Results
In the attention network, disruption of interhemispheric FC was significantly correlated with abnormal detection of visual stimuli (Pearson r with field effect = −0.624, p = 0.002). In the somatomotor network, disruption of interhemispheric FC was significantly correlated with upper extremity impairment (Pearson r with contralesional Action Research Arm Test = 0.527, p = 0.036). In contrast, intrahemispheric FC within the normal or damaged hemispheres was not correlated with performance in either network. Quantitative lesion analysis demonstrated that our results could not be explained by structural damage alone.
Interpretation
These results suggest that lesions cause state changes in the spontaneous functional architecture of the brain, and constrain behavioral output. Clinically, these results validate using FC for assessing the health of brain networks, with implications for prognosis and recovery from stroke, and underscore the importance of interhemispheric interactions. ANN NEUROL 2010;67:365–375
Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly ...defined GBM subtypes.
MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. IDH1 mutational and MGMT promoter methylation status were determined by DNA sequencing and methylation-specific PCR, respectively. Overall survival was determined by using a multivariate Cox model and the Kaplan-Meier method with a log rank test. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features.
MGMT promoter methylation and IDH1 mutation were associated with longer median survival. Edema levels stratified survival for methylated but not unmethylated tumors. Median survival for methylated tumors with little/no edema was 2476 days (95% CI, 795), compared with 586 days (95% CI, 507-654) for unmethylated tumors or tumors with edema. All IDH1 mutant tumors were nCET positive, and most (11/14, 79%) were located in the frontal lobe. Imaging features including larger tumor size and nCET could be used to determine IDH1 mutational status with 97.5% accuracy, but poorly predicted MGMT promoter methylation.
Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation. Edema stratifies survival in MGMT promoter methylated but not in unmethylated tumors; patients with methylated tumors with little or no edema have particularly long survival.
Shifts of attention to unattended stimuli (stimulus-driven reorienting) are often studied by measuring responses to unexpected stimuli, confounding reorienting and expectation. We separately measured ...the blood-oxygenation-level-dependent signal for both factors by manipulating the probability of salient visual cues that either shifted attention away from or maintained attention on a stream of visual stimuli. The results distinguished three networks recruited by reorienting. Right temporoparietal junction (TPJ), the posterior core of a ventral frontoparietal network, was activated more by cues for shifting than maintaining attention independently of cue location and probability, acting as a switch. TPJ was separately modulated by low probability cues, which signaled a breach of spatial expectation, independently of whether they shifted attention. Under resting conditions, TPJ activity was correlated resting-state functional connectivity magnetic resonance imaging, (rs-fcMRI) with right inferior frontal gyrus (IFG), an anterior component of the ventral network. Nevertheless, IFG was activated only by unexpected shifts of attention, dissociating its function from TPJ. Basal ganglia and frontal/insula regions also were activated only when reorienting was unexpected but showed strong rs-fcMRI among themselves, not with TPJ/IFG, defining a distinct network that may retrieve/activate commands for shifting attention. Within dorsal frontoparietal regions, shifting attention produced sustained spatially selective modulations in intraparietal sulcus (IPS) and frontal-eye field (FEF), and transient less selective modulations in precuneus and FEF. Modulations were observed even when reorienting was likely, but increased when reorienting was unexpected. The latter result may partly reflect interactions with lateral prefrontal components of the basal-ganglia/frontal/insula network that showed significant rs-fcMRI with the dorsal network.
Excessive daytime sleepiness (EDS) occurs frequently in adult patients with obstructive sleep apnea (OSA). However, the incidence of EDS in children with OSA is unknown.
To determine overall daytime ...sleepiness in pediatric OSA, 54 children with OSA, 14 children with primary snoring (PS), and 24 controls (C) underwent an overnight diagnostic polysomnogram followed the next day by a multiple sleep latency test.
The mean apnea index was 15.1 +/- 9.5 standard deviation in OSA, 1.1 +/- 0.5 in PS, and 0.1 +/- 0.3 in C. Mean sleep latencies were 23.7 +/- 3.0 minutes in C, 23.7 +/- 3.1 minute in PS, and 20.0 +/- 7.1 minute in OSA patients. However, only 7 children with OSA had mean sleep latencies <10 minutes. In addition, shorter sleep latencies were more likely to occur in more obese OSA patients and those with more severe apnea index, and oxyhemoglobin desaturation.
Shortened sleep latencies occur in children with OSA, but EDS is infrequent and tends to develop among more severe and/or obese patients.
Bevacizumab has been shown to be effective in the treatment of recurrent glioblastoma in combination with chemotherapy compared with historic controls but not in randomized trials.
We conducted a ...retrospective analysis of patients treated for recurrent glioblastoma with bevacizumab vs a control group of patients, comparing progression-free survival (PFS) and overall survival (OS) between the two groups, and performed subgroup analysis based on age and performance status. Expression of vascular endothelial growth factor (VEGF) based on age was examined using DNA microarray analysis. We also evaluated the impact of bevacizumab on quality of life.
We identified 44 patients who received bevacizumab and 79 patients who had not been treated with bevacizumab. There was a significant improvement in PFS and OS in the bevacizumab-treated group. Patients of older age (> or =55 years) and poor performance status (Karnofsky Performance Status < or =80) had significantly better PFS when treated with bevacizumab, and bevacizumab-treated older patients had significantly increased OS. VEGF expression was significantly higher in older glioblastoma patients (aged > or =55 years). Patients treated with bevacizumab also required less dexamethasone use and maintained their functional status longer than the control group.
Bevacizumab in combination with chemotherapy may be a more effective treatment for recurrent glioblastoma and warrants further randomized prospective studies to determine its effect on survival. Bevacizumab also has more effect in those with older age and might reflect biologic differences in glioblastoma in different age groups as seen with the expression of vascular endothelial growth factor.
Obstructive sleep apnea syndrome in young children is associated with an adverse effect on learning. However, the long-term impact of sleep-disordered breathing (SDB) during early childhood on ...learning remains unknown.
Questionnaires were mailed to seventh and eighth graders attending public schools whose class ranking was either in the top 25% (high performance HP) or bottom 25% of their class (low performance LP), and who were matched for age, gender, race, school, and street of residence. Snoring frequency and loudness at 2 to 6 years of age, tonsillectomy and adenoidectomy (T&A) for snoring or recurrent infection, school grades, and parental smoking and snoring were assessed.
The questionnaire response rate was 82.8%. Because of ongoing ring, 13 responders were excluded, such that 1588 questionnaires could be analyzed (797 in LP and 791 in HP group). Frequent and loud snoring during early childhood was reported in 103 LP children (12.9%) compared with 40 HP children (5.1%; odds ratio: 2.79; confidence interval: 1.88-4.15). Furthermore, 24 LP and 7 HP children underwent T&A for snoring (odds ratio: 3.40; confidence interval: 1.47-7.84), while 21 LP and 19 HP children required surgery for recurrent tonsillitis.
Children with lower academic performance in middle school are more likely to have snored during early childhood and to require T&A for snoring compared with better performing schoolmates. These findings support the concept that SDB-associated neurocognitive morbidity may be only partially reversible or that a "learning debt" may develop with SDB during early childhood and hamper subsequent school performance.
Patients with recurrent gliomas (n = 14) were treated with bevacizumab and carboplatin, cpt-11, or etoposide. Follow-up MRI scans were obtained 2 to 6 weeks after initiation of treatment. ...Contrast-enhancing tumor shrank in 7 patients, with reductions evident in as little as 2 weeks after initiation of therapy. Treatment seemed more effective for heterogeneously enhancing tumor compared with solidly enhancing tumor.
The bis(imino)pyridine iron complex, for the first time, is developed as an effective metal carbene catalyst for carbene transfer reactions of donor-acceptor diazo compounds. Its broad catalytic ...capability is demonstrated by a range of metal carbene reactions, from cyclopropanation, cyclopropenation, epoxidation, and Doyle-Kirmse reaction to O-H insertion, N-H insertion, and C-H insertion reactions. The asymmetric cyclopropanation of styrene and methyl phenyldiazoacetate was successfully achieved by the new chiral bis(imino)pyridine iron catalyst, which delivers a new gateway for the development of chiral iron catalysis for metal carbene reactions.
The bis(imino)pyridine iron complex, for the first time, is developed as an effective metal carbene catalyst for carbene transfer reactions of donor-acceptor diazo compounds.
Currently it is difficult to predict tumor response to anti-angiogenic therapy in individual patients. Our aim was to determine if ADC histogram analysis can stratify progression-free and overall ...survival in patients with newly diagnosed GBM treated "up-front" (ie, before tumor recurrence) with bevacizumab.
Up-front bevacizumab-treated and control patients (n = 59 and 62, respectively) with newly diagnosed GBM were analyzed by using an ADC histogram approach based on enhancing tumor. Progression-free and overall survival was determined by using Cox proportional HRs and the Kaplan-Meier method with logrank and Wilcoxon tests.
For up-front bevacizumab-treated patients, lower ADC(L) was associated with significantly longer progression-free survival (median, 459 days for ADC(L) < 1200 versus 315 days for ADC(L) ≥ 1200 10(-6)mm(2)/s; P = .008, logrank test) and trended with longer overall survival (581 versus 429 days, P = .055). ADC values did not stratify progression-free or overall survival for patients in the control group (P = .92 and P = .22, respectively). Tumors with MGMT promoter methylation had lower ADC(L) values than unmethylated tumors (mean, 1071 versus 1183 10(-6)mm(2)/s; P = .01, 2-group t test).
Pretreatment ADC histogram analysis can stratify progression-free survival in bevacizumab-treated patients with newly diagnosed GBM. Lower ADC is associated with tumor MGMT promoter methylation, which may, in part, account for the favorable outcome associated with low ADC(L) tumors.
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