The medial prefrontal cortex is critical for memory retrieval and resolving interference.

The prefrontal cortex (PFC) is known to be critically involved in strategy switching, attentional set shifting, and inhibition of prepotent responses. A central feature of this kind of behavioral flexibility is the ability to resolve conflicting response tendencies, suggesting a general role of the PFC in resolving interference. If so, the PFC should also be involved in memory retrieval, which involves competition between potential retrieval targets. Moreover, the PFC should be needed whenever interference is high, regardless of the strategic or attentional requirements of the task. To test this hypothesis, we temporarily inactivated the mPFC with muscimol and tested rats on several olfactory learning tasks. Rats given muscimol were able to learn a few discrimination problems when they were learned one at a time. However, they were severely impaired when they had to learn and remember many odors concurrently. Rats given muscimol also suffered greater interference when learning two lists of conflicting odor discrimination problems. Additionally, temporary mPFC inactivation during the acquisition of one set of odor memories actually improved the ability to learn a new set of conflicting odor memories. This paradoxical release from interference suggests that the mPFC plays an important role in acquiring and promoting the long term retrieval of memories. These results suggest that the mPFC plays a general role in resolving interference and that this is a key aspect of behavioral flexibility.

Intravitreal ranibizumab for polypoidal choroidal vasculopathy in non-Asian patients.

PURPOSE: To determine safety, tolerability, and efficacy of intravitreal ranibizumab in the treatment of polypoidal choroidal vasculopathy in a non-Asian population. METHODS: Phase I/II, prospective, open-label, single-center, nonrandomized, uncontrolled, consecutive, interventional case series of 20 eyes in 19 patients with exudative active polypoidal choroidal vasculopathy. Eyes received 3 monthly intravitreal ranibizumab injections (0.3 or 0.5 mg), with additional ranibizumab injections, observation, or alternative treatments at investigators' discretion, through 24 months. Main outcome measures were ocular and systemic safety and mean change from baseline in best-corrected visual acuity and center point thickness. RESULTS: Visually significant ocular adverse events included cataract progression (n = 3), mild vitreous hemorrhage (n = 2), and macular hole (n = 1). No systemic drug-related adverse events were observed. Mean baseline best-corrected visual acuity was 20/127 (range, 20/16-20/500) and center point thickness was 298 µm. Mean best-corrected visual acuity increased from baseline by 1.2 Snellen lines at 12 months and 24 months. Mean center point thickness decreased by 53 µm and 67 µm from baseline at 12 months and 24 months, respectively. CONCLUSION: Intravitreal ranibizumab was well tolerated in non-Asian patients with polypoidal choroidal vasculopathy; the majority of eyes experienced improvements in best-corrected visual acuity and center point thickness after ranibizumab treatment.