Extensive research has established the relationship between individual differences in brain activity in a resting state and individual differences in behavior. Conversely, when individuals are engaged in various tasks, certain task-evoked reorganization occurs in brain functional connectivity, which consequently can influence individuals' performance as well. Here, we show that resting state and task-dependent state brain patterns interact as a function of contexts engendering stress. Findings revealed that when the resting state connectome was examined during performance, the relationship between connectome strength and performance only remained for participants under stress (who also performed worse than all other groups on the math task), suggesting stress preserved brain patterns indicative of underperformance whereas non-stressed individuals spontaneously transitioned out of brain patterns indicative of underperformance. These findings were subsequentially replicated in an independent sample set. Implications are discussed for network dynamics as a function of context.
The developing cerebral cortex undergoes rapid microstructural and morphological changes throughout the third trimester. Recently, increased attention has been focused on the identification of imaging features that represent the underlying cortical cyto/myeloarchitecture driving intracortical myelination and the maturation of cortical gray matter (GM) and its adjacent superficial white matter (sWM). However, the characterization and spatiotemporal pattern of complex cyto/myeloarchitectural changes in this critical time period remain incompletely understood. Using 92 MRI scans from 78 preterm neonates (baseline: n = 78, postmenstrual age=33.1+/-1.8 weeks; follow-up: n=14, 37.3+/-1.3), the current study leveraged combined T1/T2 intensity ratio and diffusion tensor imaging (DTI) measurements, including fractional anisotropy (FA) and mean diffusivity (MD), to characterize the cyto/myeloarchitectural architecture of cortical GM and its adjacent sWM in preterm neonates. DTI metrics during these weeks showed an overall linear developmental trajectory: FA decreased along with time in GM but increased in sWM; MD decreased in both GM and sWM. In contrast, T1/T2 measurements showed a distinctive parabolic developmental trajectory, revealing additional cyto/myeloarchitectural signature inferred. Furthermore, the spatiotemporal courses of T1/T2 ratio and DTI parameters were found to be regionally heterogeneous across the cerebral cortex, suggesting these imaging features specific relationship to regional cyto/myeloarchitectural maturation: faster T1/T2 ratio changes were found in the central, ventral, and temporal regions of GM and sWM, faster FA increases in anterior sWM areas, and faster MD decreases in GM and sWM central and cingulate areas. Taken together, our results may offer an explanation of the novel pattern of cyto/myeloarchitectural processes observed throughout the third trimester, including dendritic arborization, synaptogenesis, glial proliferation, as well as radial glial cell organization and apoptosis. Finally, T1/T2 ratio and DTI measurements were significantly associated with 1 year outcome scores of language and cognitive performance as well as perinatal clinical conditions, including intraventricular hemorrhage and chronic lung disease, demonstrating their potential as imaging biomarkers characterizing microstructural deviation in atypical neurodevelopment. Ultimately, with combined properties of cortical T1/T2 and DTI measurements, this study provides unique insights into the cellular processes and associated developmental mechanisms during the critical development of the third trimester.
4627 Background: ChemoRT after surgery for locally advanced gastric cancer improves overall and relapse-free survival (OS and RFS) compared to observation (NEJM 2000,345:725–30). However, loco-regional recurrences (>50%) remain high and we hypothesized that adding IP FUDR would further improve outcome. Methods: Patients (pts) ECOG performance status (PS) 0–2, gastric/gastroesphogeal(GEJ) adenocarcinoma stage Ib-IV (M0) undergoing R0 resection were eligible, and had insertion of IP catheters at surgery. IP FUDR(3gm/dose/day) was given on protocol days 1, 2, 3 and 15, 16, 17 prior to 5-FU/LV and external beam RT (45Gy) as in cited study. Simon 2-stage optimum design was used to demonstrate safety. Endpoints also included were loco-regional recurrence and survival. Results: 28 pts with gastric/GEJ adenocarcinoma (25/3) were enrolled from 2002 to 2006 at 2 institutions: median age 59.5 years (range 39–81), M /F (21/7). R0 gastric resection was performed with dissection of median 22 (range 8–102) lymph nodes(LN’s). 22/28 pts were lymph node positive. Full dose IP FUDR was completed in 20/28 pts. 4 pts required dose reduction (1 for grade(gr) 2 hepatic enzyme elevation, 2 gr 2 neutropenia, 1 gr 4 neutropenia), 3 discontinued therapy (1 gr 3 abdominal pain, 1 GI abscess, and 1 bleeding arterial pseudoaneurysm). One pt received no IP treatment due to catheter failure. 24/28 pts completed chemoRT and had toxicity comparable to that previously reported in the Intergroup 0116 trial. At 26 month median follow up (range 2.8–43.4), of the 26 pts evaluable for response, 16 pts are NED, 6 alive with disease, 3 dead of disease, and 1 dead from other cause. 5 recurrences were intra-abdominal, 1 local, 2 distant, and 1 at multiple sites. At present analysis, the median RFS is 32.5 months. Conclusions: IP FUDR prior to chemoRT after R0 gastric cancer resection is well tolerated. A randomized study to test its role in reducing regional recurrence and improving outcome is warranted. (FDA Orphan Products grant# FD-R-2150–04) No significant financial relationships to disclose.
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