The medial temporal lobes, prefrontal cortex, and parts of parietal cortex form the neural underpinnings of episodic memory, which includes remembering both where and when an event occurred. Yet how these three key regions interact during retrieval of spatial and temporal context remains largely untested. Here, we employed simultaneous electrocorticographical recordings across multiple lobular regions, employing phase synchronization as a measure of network functional connectivity, while patients retrieved spatial and temporal context associated with an episode. Successful memory retrieval was characterized by greater global connectivity compared to incorrect retrieval, with the MTL acting as a convergence hub for these interactions. Spatial vs. temporal context retrieval resulted in prominent differences in both the spectral and temporal patterns of network interactions. These results emphasize dynamic network interactions as central to episodic memory retrieval, providing novel insight into how multiple contexts underlying a single event can be recreated within the same network.

The authors have presented several aspects of using new techniques to visualize electrodes implanted for localizing epilepsy. The ability to use automated labeling schemas to denote which gyrus a particular electrode overlies is potentially of great utility in planning resections and in corroborating the results of extraoperative stimulation mapping. Dilation of the pial mesh model provides, for the first time, a sense of the cortical surface not sampled by the electrode, and the potential roles this "electrophysiologically hidden" cortex may play in both eloquent function and seizure onset.

The right inferior frontal cortex (rIFC) is important for stopping responses. Recent research shows that it is also activated when response emission is slowed down when stopping is anticipated. This suggests that rIFC also functions as a goal-driven brake. Here, we investigated the causal role of rIFC in goal-driven braking by using computer-controlled, event-related (chronometric), direct electrical stimulation (DES). We compared the effects of rIFC stimulation on trials in which responses were made in the presence versus absence of a stoppinggoal ("Maybe Stop" [MS] vs "No Stop" [NS]). We show that DES of rIFC slowed down responses (compared with control-site stimulation) and that rIFC stimulation induced more slowing when motor braking was required (MS) compared with when it was not (NS). Our results strongly support a causal role of a rIFC-based network in inhibitory motor control. Importantly, the results extend this causal role beyond externally driven stopping to goal-driven inhibitory control, which is a richer model of human self-control. These results also provide the first demonstration of double-blind chronometric DES of human prefrontal cortex, and suggest that-in the case of rIFC-this could lead to augmentation of motor braking.

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Pancreatic cancer continues to have a dismal prognosis and novel therapy is needed. In this study, we evaluate a promising new target for therapy, phosphatidylserine (PS). PS is an anionic phospholipid located normally on the inner leaflet of the plasma membrane in mammalian cells. In the tumor microenvironment, PS becomes externalized on vascular endothelium. The monoclonal antibody 3G4 binds PS and promotes an inflammatory response against tumor blood vessels, resulting in reduction of tumor growth. Mice with orthotopic pancreatic tumors were treated with 3G4, gemcitabine or a combination of both drugs. Tumor burden including pancreas weight and metastatic lesions (liver, lymph node and peritoneal) were reduced 3-to 5-fold by the combination therapy as compared with 1.5-to 2-fold with 3G4 and gemcitabine alone, respectively. Treatment of tumor-bearing animals with the combination therapy increased macrophage infiltration into the tumor mass 10-fold and reduced microvessel density in the tumor by 2.5-fold compared with tumors from untreated animals. Gemcitabine alone and 3G4 alone were less effective than the combination of the 2 agents together. The additive therapeutic effect of both agents appears to be because chemotherapy increases PS exposure on tumor vascular endothelium and amplifies the target for attack by 3G4. In conclusion, 3G4 enhanced the anti-tumor and anti-metastatic activity of gemcitabine without contributing to toxicity. ' 2005 Wiley-Liss, Inc.