Early survival and delayed death of developmentally-born dentate gyrus neurons.

The storage and persistence of memories depends on plasticity in the hippocampus. Adult neurogenesis produces new neurons that mature through critical periods for plasticity and cellular survival, which determine their contributions to learning and memory. However, most granule neurons are generated prior to adulthood; the maturational timecourse of these neurons is poorly understood compared to adult-born neurons but is essential to identify how the dentate gyrus (DG), as a whole, contributes to behavior. To characterize neurons born in the early postnatal period, we labeled DG neurons born on postnatal day 6 (P6) with BrdU and quantified maturation and survival across early (1 hr to 8 weeks old) and late (2-6 months old) cell ages. We find that the dynamics of developmentally-born neuron survival is essentially the opposite of neurons born in adulthood: P6-born neurons did not go through a period of cell death during their immature stages (from 1 to 8 weeks). In contrast, 17% of P6-born neurons died after reaching maturity, between 2 and 6 months of age. Delayed death was evident from the loss of BrdU+ cells as well as pyknotic BrdU+ caspase3+ neurons within the superficial granule cell layer. Patterns of DCX, NeuN, and activity-dependent Fos expression indicate that developmentally-born neurons mature over several weeks and a sharp peak in zif268 expression at 2 weeks suggests that developmentally-born neurons mature faster than adult-born neurons (which peak at 3 weeks). Collectively, our findings are relevant for understanding how developmentally-born DG neurons contribute to memory and disorders throughout the lifespan. High levels of early survival and zif268 expression may promote learning, while also rendering neurons sensitive to insults at defined stages. Late neuronal death in young adulthood may result in the loss of hundreds of thousands of DG neurons, which could impact memory persistence and contribute to hippocampal/DG atrophy in disorders such as depression.

The presence of joint predictors generates conjunctive predictions.

The cognitive system readily detects statistical relationships where a cue predicts a specific outcome. What is less known is how the mind generates predictions when multiple cues are presented simultaneously that predict different outcomes. Here, we examine the nature of such predictions. Specifically, we examine whether the presence of joint cues leads to conjunctive predictions that represent the overlap between the outcomes associated with the cues, or disjunctive predictions that represent the total possible outcomes. To test this, we used a visual search paradigm where participants first viewed a cue and then searched for a target in an array. Each cue predicted where the target would appear in one of the four quadrants in the array. After learning the cue-location associations, two cues were presented simultaneously, and participants searched for the target where the target now appeared in each quadrant with equal probability. We found that participants were faster to find the target in conjunctive locations over disjunctive ones upon seeing two cues (Experiment 1). This attentional prioritization was not solely driven by the smaller spatial scope of conjunctive locations (Experiment 2), and was present when two cues were presented in two feature dimensions in a single object (Experiment 3). These results were consistent with a conjunctive account, where the presence of joint cues led to a conjunctive prediction that represented the overlap of the different outcomes associated with each cue. The study sheds a new light on how the mind makes predictions in novel contexts based on existing knowledge.

Perception of multi-dimensional regularities is driven by salience.

A challenge for the visual system is to detect regularities from multiple dimensions of the environment. Here we examine how regularities in multiple feature dimensions are distinguished from randomness. Participants viewed a matrix containing a structured half and a random half, and judged whether the boundary between the two halves was horizontal or vertical. In Experiments 1 and 2, the cells in the matrix varied independently in the color dimension (red or blue), the shape dimension (circle or square), or both. We found that boundary discrimination accuracy was higher when regularities were present in the color dimension than in the shape dimension, but the accuracy was the same when regularities were present in the color dimension alone or in both dimensions. By adding a third surface dimension (hollow or filled) in Experiments 3 and 4, we found that discrimination accuracy was higher when regularities were present in the surface dimension than in the color dimension, but was the same when regularities were present in the surface dimension alone or in all three dimensions. Moreover, when there were two conflicting boundaries, participants chose the boundary defined by the surface dimension, followed by the color dimension as more visible than the shape dimension (Experiments 5 and 6). Finally, participants were faster at detecting differences in the surface dimension, followed by the color and the shape dimensions (Experiments 7 and 8). These results suggest that perception of regularities in multiple feature dimensions is driven by the presence of regularities in the most salient feature dimension.

Adult neurogenesis promotes efficient, nonspecific search strategies in a spatial alternation water maze task.

Goal-directed navigation requires learning strategies that are efficient and minimize costs. In some cases it may be desirable to flexibly adjust behavioral responses depending on the cues that vary from one episode to the next. In others, successful navigation might be achieved with inflexible, habit-like responses that reduce cognitive load. Adult neurogenesis is believed to contribute to the spatial processing functions of the hippocampus, particularly when behavioral flexibility is required. However, little is known about the role of neurogenesis in spatial navigation when goals are unpredictable or change repeatedly according to certain rules. We hypothesized that neurogenesis is necessary in a spatial navigation task that involves different patterns of reinforcement. Intact and neurogenesis-deficient rats were trained to escape to one of two possible platform locations in a spatial water maze. The platform either repeated in the same location for all trials in a day, alternated between two locations across trials, or randomly moved between the two locations. Neurogenesis selectively enhanced escape performance in the alternating condition, but not by improving platform choice accuracy. Instead, neurogenesis-intact rats made fewer search errors and developed an efficient habit-like strategy where they consistently swam to a preferred location. If the platform was not present, they proceeded to the other possible location. In contrast, neurogenesis-deficient rats were indecisive and navigationally less-efficient. Thus, in conditions where goals follow a predictable spatiotemporal pattern, adult neurogenesis promotes the adoption of navigation strategies that are spatially nonspecific but, nonetheless, accurate and efficient.

Alternation blindness in the representation of binary sequences.

Binary information is prevalent in the environment and contains 2 distinct outcomes. Binary sequences consist of a mixture of alternation and repetition. Understanding how people perceive such sequences would contribute to a general theory of information processing. In this study, we examined how people process alternation and repetition in binary sequences. Across 4 paradigms involving estimation, working memory, change detection, and visual search, we found that the number of alternations is underestimated compared with repetitions (Experiment 1). Moreover, recall for binary sequences deteriorates as the sequence alternates more (Experiment 2). Changes in bits are also harder to detect as the sequence alternates more (Experiment 3). Finally, visual targets superimposed on bits of a binary sequence take longer to process as alternation increases (Experiment 4). Overall, our results indicate that compared with repetition, alternation in a binary sequence is less salient in the sense of requiring more attention for successful encoding. The current study thus reveals the cognitive constraints in the representation of alternation and provides a new explanation for the overalternation bias in randomness perception. (PsycINFO Database Record

Implicit updating of object representation via temporal associations.

The cognitive system can flexibly update the representations of objects upon changes in the physical properties of the objects. Can the changes ripple to the representations of other associated objects that are not directly observable? We propose that statistical learning allows changes in one object to be automatically transferred to related objects. Observers viewed a temporal sequence with pairs of colored circles where the first circle always preceded the second. When the first circle increased or decreased in size, the second circle was judged to be larger (or smaller), suggesting that changes were automatically transferred to the second object (Experiment 1). When the second circle changed in size, the first circle was unaffected (Experiment 2). The strength of transfer seemed to depend on the conditional probability between objects (Experiment 3). The findings were replicated using pairs of faces that changed in expressions (Experiments 4&5). Importantly, no observer was explicitly aware of the pairs. Thus, statistical learning enables automatic and implicit updating of object representations upon changes to temporally associated objects.

The consistency of the subjective concept of randomness.

A pervasive bias in the subjective concept of randomness is that people often expect random sequences to exhibit more alternations than produced by genuine random processes. What is less known is the stability of this bias. Here, we examine two important aspects of the over-alternation bias: first, whether this bias is present in stimuli that vary across feature dimensions, sensory modalities, presentation modes and probing methods, and, second, how consistent the bias is across these stimulus variations. In Experiment 1, participants adjusted sequences until they looked maximally random. The sequences were presented as temporal streams of colors, shapes, auditory tones or tiled as spatial matrices. In Experiment 2, participants produced random matrices by adjusting the color of each cell. We replicated the findings using a within-subjects design in Experiment 3. We found that participants judged and produced over-alternating stimuli as the most random. Importantly, this bias was consistent across presentation modes (temporal vs spatial), feature dimensions (color vs shape), sensory modalities (visual vs auditory), speed (fast vs slow), stimulus size (small vs large matrices) and probing methods (adjusting the generating process vs individual bits). Overall, the results suggest that the subjective concept of randomness is highly stable across stimulus variations.

Differential Effects of Extended Exercise and Memantine Treatment on Adult Neurogenesis in Male and Female Rats.

Adult neurogenesis has potential to ameliorate a number of disorders that negatively impact the hippocampus, including age-related cognitive decline, depression, and schizophrenia. A number of treatments enhance adult neurogenesis including exercise, NMDA receptor antagonism, antidepressant drugs and environmental enrichment. Despite the chronic nature of many disorders, most animal studies have only examined the efficacy of neurogenic treatments over short timescales (≤1 month). Also, studies of neurogenesis typically include only 1 sex, even though many disorders differentially impact males and females. We tested whether two known neurogenic treatments, running and the NMDA receptor antagonist, memantine, could cause sustained increases in neurogenesis in male and female rats. We found that continuous access to a running wheel (cRUN) initially increased neurogenesis, but effects were minimal after 1 month and completely absent after 5 months. Similarly, a single injection of memantine (sMEM) transiently increased neurogenesis before returning to baseline at 1 month. To determine whether neurogenesis could be increased over a 2-month timeframe, we next subjected rats to interval running (iRUN), multiple memantine injections (mMEM), or alternating blocks of iRUN and mMEM. Two months of iRUN increased DCX+ cells in females and iRUN followed by mMEM increased DCX+ cells in males, indicating that neurogenesis was increased in the later stages of the treatments. However, thymidine analogs revealed that neurogenesis was minimally increased during the initial stages of the treatments. These findings highlight temporal limitations and sex differences in the efficacy of neurogenic manipulations, which may be relevant for designing plasticity-promoting treatments.

Statistical regularities reduce perceived numerosity.

Numerical information can be perceived at multiple levels (e.g., one bird, or a flock of birds). The level of input has typically been defined by explicit grouping cues, such as contours or connecting lines. Here we examine how regularities of object co-occurrences shape numerosity perception in the absence of explicit grouping cues. Participants estimated the number of colored circles in an array. We found that estimates were lower in arrays containing colors that consistently appeared next to each other across the experiment, even though participants were not explicitly aware of the color pairs (Experiments 1a and 1b). To provide support for grouping, we introduced color duplicates and found that estimates were lower in arrays with two identical colors (Experiment 2). The underestimation could not be explained by increased attention to individual objects (Experiment 3). These results suggest that statistical regularities reduce perceived numerosity consistent with a grouping mechanism.

The persistence of the attentional bias to regularities in a changing environment.

The environment often is stable, but some aspects may change over time. The challenge for the visual system is to discover and flexibly adapt to the changes. We examined how attention is shifted in the presence of changes in the underlying structure of the environment. In six experiments, observers viewed four simultaneous streams of objects while performing a visual search task. In the first half of each experiment, the stream in the structured location contained regularities, the shapes in the random location were randomized, and gray squares appeared in two neutral locations. In the second half, the stream in the structured or the random location may change. In the first half of all experiments, visual search was facilitated in the structured location, suggesting that attention was consistently biased toward regularities. In the second half, this bias persisted in the structured location when no change occurred (Experiment 1), when the regularities were removed (Experiment 2), or when new regularities embedded in the original or novel stimuli emerged in the previously random location (Experiments 3 and 6). However, visual search was numerically but no longer reliably faster in the structured location when the initial regularities were removed and new regularities were introduced in the previously random location (Experiment 4), or when novel random stimuli appeared in the random location (Experiment 5). This suggests that the attentional bias was weakened. Overall, the results demonstrate that the attentional bias to regularities was persistent but also sensitive to changes in the environment.

[Effects of early rehabilitation on activities of daily living and complications in acute stroke patients].

OBJECTIVE: To investigate the effects of early rehabilitation on activities of daily living (ADL) and complications in patients within 1 month after a first stroke. METHODS: 57 stroke patients were randomly divided into rehabilitation group (30 cases) and control group (27 cases). Patients in rehabilitation group received rehabilitation intervention (the main methods were therapeutic exercises, especially Bobath method) starting on average (15+/-4) days after stroke. Patients in both groups received the similar pharmological treatments. The demographic information was similar in both groups. Using the degree of deficit of neural function (DDNF,Chinese version), Barthel index and Fugl-Meyer Assessment (FMA) scale to assess all patients in pre-therapy stage and post-therapy stage. RESULTS: The scores of DDNF, FMA and Barthel index except for the grooming item (P=0.04, it is higher in rehabilitation group than in control group) in the 2 groups were similar at the pre-therapy stage (P>0.05). At the post-therapy stage, there was no significant difference in the difference values in the grooming item between the pre- and post-stages in the 2 groups. There were significant differences in the difference values between the pre- and post-stages in the 2 groups in eating, bed-chair transfer and short distance walking activities items put together(P=0.05). The differences between the pre- and post-stages in both groups in Barthel index items except the control of feces and urine, and bath items were significant (P