An fMRI Investigation of Source Memory in Obsessive-Compulsive Disorder

Individuals with Obsessive-Compulsive Disorder (OCD) often complain about poor memory and evidence suggests that individuals with OCD exhibit deficits on some tasks, including those that are unrelated to obsessional concerns. As individuals with OCD tend to focus on details and miss the larger context, the construct of source (contextual) memory may be particularly relevant to memory complaints in OCD. Memory for different types of information (object versus contextual information) may rely on distinct regions within the prefrontal cortex and medial temporal lobe, and may be differentially impacted by obsessive-compulsive symptoms. Using a novel task, 16 individuals with OCD and 17 age, education, and gender matched healthy control group participants studied objects in the context of four rooms. While undergoing functional Magnetic Resonance Imaging (fMRI), participants completed source and object recognition testing. While no significant differences were found between the two groups in terms of behavioral performance, individuals with OCD exhibited greater task related activation in the left medial prefrontal cortex, premotor cortex, dorsolateral prefrontal cortex, right parietal region, and posterior cingulate cortical areas relative to healthy controls during correct source verses object recognition trials. Results are discussed in terms of compensatory activation and altered activation patterns in individuals with OCD

Source Memory in Individuals with Subclinical Obsessive-Compulsive Symptoms

Patients with obsessive-compulsive disorder often complain of poor memory and results of neuropsychological research have demonstrated impairments, particularly on tasks involving strategic processing. Past research has relied heavily on highly structured tasks where subjects are told exactly what to do. However, memory deficits may be more apparent for unstructured visuospatial tasks. This study examined performance on such a task. In the present study we sought to test source and item memory using an ecologically valid paradigm -The Memory for Rooms Test (MFRT) - a four-room task in which participants attempted to remember objects in the context of rooms. In addition, we sought to examine verbal and nonverbal memory in individuals with subclinical OCD using the California Verbal Learning Test (CVLT) and Rey-Osterrieth Complex Figure Test (RCFT). On the MFRT, Individuals with subclinical OC symptoms performed more poorly on item recognition. No impairments were found in terms of source memory. On the CVLT and RCFT, individuals with subclinical obsessive symptoms were less likely to utilize efficient organizational strategies. Our results demonstrate impairments in some aspects of organization and memory in individuals with subclinical obsessive-compulsive symptoms

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival