The influence of early aging on eye movements during motor simulation

Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging

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

Skill Memory Escaping from Distraction by Sleep—Evidence from Dual-Task Performance

BackgroundSleep facilitates off-line consolidation of memories, as shown for learning of motor skills in the absence of concomitant distractors. We often perform complex tasks focusing our attention mostly on one single part of them. However, we are equally able to skillfully perform other concurrent tasks. One may even improve performance on disregarded parts of complex tasks, which were learned implicitly. In the present study we investigated the role of sleep in the off-line consolidation of procedural skills when attention is diverted from the procedural task because of interference from a concurrent task.Methodology/Principal FindingsWe used a dual-task paradigm containing (i) procedural serial reaction time task (SRTT), which was labeled as subordinate and unimportant and (ii) declarative word-pair association task (WPAT), performed concomitantly. The WPAT served as a masked distractor to SRTT and was strongly reinforced by the instructions. One experimental and three control groups were tested. The experimental group was re-tested after two nights of sleep (sleep group, SG). The first control group had sleep deprivation on the first post-learning night (nighttime-awake group, NA), the second control group was tested in the morning and then re-tested after 12-hours (daytime-awake group, DA); the third one had the same assignments as DA but with a subsequent, instead of a concomitant, WPAT (daytime-awake-subsequent-WPAT group, DAs). We found SRTT performance gains in SG but not in NA and DA groups. Furthermore, SG reached similar learning gains in SRTT as the DAs group, which gained in SRTT performance because of post-training interference from the declarative task.Conclusions/SignificanceThe results demonstrate that sleep allows off-line consolidation, which is resistant to deteriorating effects of a reinforced distractor on the implicit procedural learning and allowing for gains which are consistent with those produced when inhibited declarative memories of SRTT do not compete with procedural ones

Means and standard error of mean (SEM) percentages for correct word-pairs recalls during the SRTT processing, in training and retrieval sessions.

<p>Differences between both sessions are also shown.</p

Experimental procedure.

<p>The experiment consisted of a <i>Training</i> followed by a <i>Retrieval</i> session. Sleep group (<i>SG</i>), nighttime-awake group (<i>NA</i>) and daytime-awake group (<i>DA</i>) performed a dual task (concomitant SRTT and WPAT; upper part). The daytime-awake-subsequent-WPAT group (<i>DAs</i>) performed a single task (SRTT alone then followed by the WPAT; lower part). <i>Training session (left part)</i>. SRTT was arranged in blocks (in yellow), for which the trial sequence was <i>fixed</i>, followed by blocks (in green) with <i>random</i> sequences of trials. Numbers in the bottom mark block’s position in the general sequence whereas, numbers on the top indicate the number of trials administered within each block. “Practice” (light blue) indicates the initial practice block, which was not included in the analyses. The WPAT (distractor task) was continuously performed throughout the entire SRTT session. The first and the last fixed sequence blocks (i.e.: block 2 and block 6), followed by the random sequence block 3 and 7, respectively were considered to investigate changes in performance across <i>Training</i>. For clarity, block 2 and block 3 were labeled as “Training 1” whereas block 6 and block 7 were labeled as “Training 2”. The difference between mean RTs to random and sequential blocks was the dependent variable being analyzed. <i>Retention interval between training and retrieval sessions (middle part)</i>. The sleep group slept the two nights after <i>Training</i> before doing <i>Retrieval</i> in the morning. The nighttime-awake group, instead, stayed awake throughout the first night after <i>Training</i> and slept the second night. The daytime-awake group trained in the morning and was retested in the evening of the same day during which they stayed awake. <i>Retrieval session (right part)</i>. Block 9 (fixed trial sequence) and block 10 (random trial sequence) were labeled as <i>Retrieval</i>. The same random minus fixed block difference as in the training session was taken to investigate the RT performance. The task was immediately followed by one bock (in purple) in which a generation task was administered.</p

Graph of SRTT performance gains across the three time-points of assessment.

<p>Delta means improvement in SRTT performances (in msec) for the four groups during the Training session (left graph) and in the Retrieval session compared to Training 2 (right graph).</p

Mean reaction times in msec (+/− SEM) for the three time-points of assessment of SRTT performance: Training 1, Training 2 and Retrieval.

<p>For each group, block number and property are reported. “delta” indicates the differences between mean reaction times in the fixed and in the following random sequence blocks.</p

Descriptive statistics and post-hoc analyses of SRTT performance across Training 1 and Training 2 and across Training 2 and Retrieval, for all groups.

<p>Beside mean and standard error of mean (SEM), the results of paired-sample <i>t</i>-tests are presented (t = t-value, p = significance value, d = Cohen’s d). In the last row, the <i>Group</i> x <i>Training</i> and <i>Group</i> x <i>Retrieval</i> interactions from the respective separate ANOVAs are reported.</p