Framework for advancing rigorous research.

There is a pressing need to increase the rigor of research in the life and biomedical sciences. To address this issue, we propose that communities of 'rigor champions' be established to campaign for reforms of the research culture that has led to shortcomings in rigor. These communities of rigor champions would also assist in the development and adoption of a comprehensive educational platform that would teach the principles of rigorous science to researchers at all career stages.

General Intelligence (g): Overview of a Complex Construct and Its Implications for Genetics Research.

Current technology has dramatically increased the prevalence of studies to establish the genetic correlates of a wide variety of human characteristics, including not only the physical attributes that determine what we look like and the risk of physiological disease but also the psychological and cognitive characteristics that often define who we are as individuals. Perhaps one of the most deeply personal and often controversial characteristics is the concept of general intelligence, known in the psychological literature as "g." As with the genetic study of any complex trait, the first step in studying the genetics of g is to carefully define the characteristic of interest. For g, this entails establishing what intelligence means and providing a clear operational definition for how it will be measured. In this paper, we provide a brief historical and theoretical overview of the construct of general intelligence, describe its relationship to the contemporary measurement of intelligence, and discuss these concepts in light of the challenges associated with defining g as a characteristic in the study of genetics.

Obligations and Concerns of an Organization Like the Center for Talented Youth.

There is another set of entities that needs to be brought into the conversation about the ethical, legal, and social implications of scientific conduct. This widely varied group includes not-for-profit educational, academic, public-service, and philanthropic organizations other than the type mentioned above as well as for-profit businesses. Despite their major differences, these organizations may all be in a position to make decisions, directly or indirectly, about the conduct of scientific research. And those decisions may have a significant impact on the parties normally involved in thinking and talking about obligations and concerns-the researchers, the subjects, and the general public. Yet there are few if any conceptual frameworks to help organizations address the ethical, legal, and social issues related to conducting scientific research. There are also few resources to help organizations find and develop the expertise required to make responsible decisions or communicate those decisions in ways that could support and advance the ethical conduct of research. In what follows, we try to identify and explore the duties, rights, and interests of one such organization, the Center for Talented Youth at Johns Hopkins University, when asked to play a supporting role in research on the genetics of intelligence. As central agents in this case, we hope to demonstrate why organizations like CTY cannot be neglected in the broader effort to ensure trustworthy research into the genetics of intelligence.

Persistent and stable biases in spatial learning mechanisms predict navigational style.

A wealth of evidence in rodents and humans supports the central roles of two learning systems--hippocampal place learning and striatal response learning--in the formation of spatial representations to support navigation. Individual differences in the ways that these mechanisms are engaged during initial encoding and subsequent navigation may provide a powerful framework for explaining the wide range of variability found in the strategies and solutions that make up human navigational styles. Previous work has revealed that activation in the hippocampal and striatal networks during learning could predict navigational style. Here, we used functional magnetic resonance imaging to investigate the relative activations in these systems during both initial encoding and the act of dynamic navigation in a learned environment. Participants learned a virtual environment and were tested on subsequent navigation to targets within the environment. We observed that a given individual had a consistent balance of memory system engagement across both initial encoding and subsequent navigation, a balance that successfully predicted the participants' tendencies to use novel shortcuts versus familiar paths during dynamic navigation. This was further supported by the observation that the activation during subsequent retrieval was not dependent on the type of solution used on a given trial. Taken together, our results suggest a model in which the place- and response-learning systems are present in parallel to support a variety of navigational behaviors, but stable biases in the engagement of these systems influence what solutions might be available for any given individual.

The role of potential agents in making spatial perspective taking social.

A striking relationship between visual spatial perspective taking (VSPT) and social skills has been demonstrated for perspective-taking tasks in which the target of the imagined or inferred perspective is a potential agent, suggesting that the presence of a potential agent may create a social context for the seemingly spatial task of imagining a novel visual perspective. In a series of studies, we set out to investigate how and when a target might be viewed as sufficiently agent-like to incur a social influence on VSPT performance. By varying the perceptual and conceptual features that defined the targets as potential agents, we find that even something as simple as suggesting animacy for a simple wooden block may be sufficient. More critically, we found that experience with one potential agent influenced the performance with subsequent targets, either by inducing or eliminating the influence of social skills on VSPT performance. These carryover effects suggest that the relationship between social skills and VSPT performance is mediated by a complex relationship that includes the task, the target, and the context in which that target is perceived. These findings highlight potential problems that arise when identifying a task as belonging exclusively to a single cognitive domain and stress instead the highly interactive nature of cognitive domains and their susceptibility to cross-domain individual differences.

Accessibility versus accuracy in retrieving spatial memory: evidence for suboptimal assumed headings.

Orientation dependence in spatial memory has often been interpreted in terms of accessibility: Object locations are encoded relative to a reference orientation that affords the most accurate access to spatial memory. An open question, however, is whether people naturally use this "preferred" orientation whenever recalling the space. We tested this question by asking participants to locate buildings on a familiar campus from various imagined locations, without specifying the heading to be assumed. We then used these pointing judgments to infer the approximate heading participants assumed at each location. Surprisingly, each location showed a unique assumed heading that was consistent across participants and seemed to reflect episodic or visual properties of the space. This result suggests that although locations are encoded relative to a reference orientation, other factors may influence how people choose to access the stored information and whether they appeal to long-term spatial memory or other more sensory-based stores.

Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment.

Elevated hippocampal activation is observed in conditions that confer risk for Alzheimer's disease, including amnestic mild cognitive impairment (aMCI). Studies in relevant animal models have indicated that overactivity in selective hippocampal circuits contributes to cognitive impairment. Here, we tested the effect of reducing hippocampal activation in aMCI. Under placebo treatment, hippocampal activation in the dentate gyrus/CA3 was elevated in aMCI patients compared to a healthy control group. By using a low dose of the antiepileptic levetiracetam hippocampal activation in aMCI was reduced to a level that did not differ from the control group. Compared to aMCI memory performance under placebo, performance in the scanning task was significantly improved under drug treatment. Contrary to the view that greater hippocampal activation might serve a beneficial function, these results support the view that increased hippocampal activation in aMCI is a dysfunctional condition and that targeting excess hippocampal activity has therapeutic potential.

Cognitive mappers to creatures of habit: differential engagement of place and response learning mechanisms predicts human navigational behavior.

Learning to navigate plays an integral role in the survival of humans and other animals. Research on human navigation has largely focused on how we deliberately map out our world. However, many of us also have experiences of navigating on "autopilot" or out of habit. Animal models have identified this cognitive mapping versus habit learning as two dissociable systems for learning a space--a hippocampal place-learning system and a striatal response-learning system. Here, we use this dichotomy in humans to understand variability in navigational style by demonstrating that brain activation during spatial encoding can predict where a person's behavior falls on a continuum from a more flexible cognitive map-like strategy to a more rigid creature-of-habit approach. These findings bridge the wealth of knowledge gained from animal models and the study of human behavior, opening the door to a more comprehensive understanding of variability in human spatial learning and navigation.

Spatial memory in the real world: long-term representations of everyday environments.

When people learn an environment, they appear to establish a principle orientation just as they would determine the "top" of a novel object. Evidence for reference orientations has largely come from observations of orientation dependence in pointing judgments: Participants are most accurate when asked to recall the space from a particular orientation. However, these investigations have used highly constrained encoding in both time-scale and navigational goals, leaving open the possibility that larger spaces experienced during navigational learning depend on a different organizational scheme. To test this possibility, we asked undergraduates to perform judgments of relative direction on familiar landmarks around their well-learned campus. Participants showed clear evidence for a single reference orientation, generally aligned along salient axes defined by the buildings and paths. This result argues that representing space involves the establishment of a reference orientation, a requirement that endures over repeated exposures and extensive experience.

Reduced hippocampal activity during encoding in cognitively normal adults carrying the APOE ɛ4 allele.

Apolipoprotein (APOE) ɛ4-related differences in memory performance have been detected before age 65. The hippocampus and the surrounding medial temporal lobe (MTL) structures are the first site affected by Alzheimer's disease (AD) and the MTL is the seat of episodic memory, including visuo-spatial memory. While reports of APOE ɛ4-related differences in these brain structures are not consistent in either cross-sectional or longitudinal structural and functional magnetic resonance imaging (fMRI) studies, there is increasing evidence that brain activity at baseline (defined as activity during fixation or rest) may differ in APOE ɛ4 carriers compared to non-carriers. In this fMRI study, cognitively normal APOE ɛ4 carriers and non-carriers engaged in a perspective-dependent spatial learning task (Shelton & Gabrieli, 2002) previously shown to activate MTL structures in older participants (Borghesani et al., 2008). A low-level, visually engaging dot-control task was used for comparison, in addition to fixation. APOE ɛ4 carriers showed less activation than non-carriers in the hippocampus proper during encoding. Specifically, when spatial encoding was contrasted against the dot-control task, encoding-related activation was significantly lower in carriers than non-carriers. By contrast, no ɛ4-related differences in the hippocampus were found when spatial encoding was compared with fixation. Lower activation, however, was not global since encoding-related activation in early visual cortex (left lingual gyrus) was not different between APOE ɛ4 carriers and non-carriers. The present data document APOE ɛ4-related differences in the hippocampus proper during encoding and underscore the role of low-level control contrasts for complex encoding tasks. These results have implications for fMRI studies that investigate the default-mode network (DMN) in middle-aged to older APOE ɛ4 carriers to help evaluate AD risk in this otherwise cognitively normal population.

Object working memory performance depends on microstructure of the frontal-occipital fasciculus.

Re-entrant circuits involving communication between the frontal cortex and other brain areas have been hypothesized to be necessary for maintaining the sustained patterns of neural activity that represent information in working memory, but evidence has so far been indirect. If working memory maintenance indeed depends on such temporally precise and robust long-distance communication, then performance on a delayed recognition task should be highly dependent on the microstructural integrity of white-matter tracts connecting sensory areas with prefrontal cortex. This study explored the effect of variations in white-matter microstructure on working memory performance in two separate groups of participants: patients with multiple sclerosis and age- and sex-matched healthy adults. Functional magnetic resonance imaging was performed to reveal cortical regions involved in spatial and object working memory, which, in turn, were used to define specific frontal to extrastriate white-matter tracts of interest via diffusion tensor tractography. After factoring out variance due to age and the microstructure of a control tract (the corticospinal tract), the number of errors produced in the object working memory task was specifically related to the microstructure of the inferior frontal-occipital fasciculus. This result held for both groups, independently, providing a within-study replication with two different types of white-matter structural variability: multiple sclerosis-related damage and normal variation. The results demonstrate the importance of interactions between specific regions of the prefrontal cortex and sensory cortices for a nonspatial working memory task that preferentially activates those regions.

Where do you think you are? Effects of conceptual current position on spatial memory performance.

Testing spatial memory within the same environment used for learning produces interference between one's immediate representation of current position and the to-be-retrieved position. In a series of 3 experiments, we show that "current position" and its influence on memory performance can be driven by conceptual factors in an ambiguous testing situation. First, we demonstrate that simple instructions about the testing conditions-"you are in the space" versus "imagine the space"-determined whether a participant showed interference from current position, reflecting the effect of one's conceived position in space on long-term memory retrieval. In addition, we show that when instructions motivate this use of current position under ambiguous conditions, the position assumed is defined by the last known position rather than the learning position. We account for these results by suggesting that current models of spatial memory need to incorporate both the perceptual and conceptual testing environment, malleable versus stable features, and the interaction of current position with long-term memory.

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study.

BACKGROUND: A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects. METHODS: In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals. RESULTS: ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation. CONCLUSIONS: Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.

Interdependent self-construal and neural representations of self and mother.

Representations of self are thought to be dynamically influenced by one's surroundings, including the culture one lives in. However, neuroimaging studies of self-representations have either ignored cultural influences or operationalized culture as country of origin. The present study used functional magnetic resonance imaging to examine the neural correlates of individual differences in interdependent self-construal. Participants rated whether trait adjectives applied to themselves or their mothers, or judged their valence or font. Findings indicated that individual differences in interdependent self-construal correlated positively with increased activation in the medial prefrontal cortex and posterior cingulated cortex when making judgments about one-self vs making judgments about one's mother. This suggests that those with greater interdependent self-construals may rely more upon episodic memory, reflected appraisals, or theory of mind to incorporate social information to make judgments about themselves.

Cognitive and neural development of individuated self-representation in children.

Processing the self-relevance of information facilitates recall. Similarly, processing close-other-related information facilitates recall to a lesser degree than processing self-relevant information. This memory advantage may be viewed as an index of the degree to which the representation of self is differentiated from representations of close others. To test developmental hypotheses concerning the self, this study examined the relation of memory for self- and mother-referentially processed information in participants age 7-13 years (Experiment 1: N = 37; Experiment 2: N = 14). Memory for words encoded with reference to oneself increases with age, relative to memory for words encoded with reference to one's mother. When used as an individual difference measure, the difference in self versus mother memory correlates with regions of the rostral anterior cingulate associated with affective salience.

Orientation dependence of spatial memory acquired from auditory experience.

The present study investigated whether memory for a room-sized spatial layout learned through auditory localization of sounds exhibits orientation dependence similar to that observed for spatial memory acquired from stationary viewing of the environment. Participants learned spatial layouts by viewing objects or localizing sounds and then performed judgments of relative direction among remembered locations. The results showed that direction judgments following auditory learning were performed most accurately at a particular orientation in the same way as were those following visual learning, indicating that auditorily encoded spatial memory is orientation dependent. In combination with previous findings that spatial memories derived from haptic and proprioceptive experiences are also orientation dependent, the present finding suggests that orientation dependence is a general functional property of human spatial memory independent of learning modality.

Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers.

The apolipoprotein varepsilon4 allele (APOE*4) is a major genetic risk factor for Alzheimer's disease (AD) and has been associated with altered cortical activation as assessed by functional neuroimaging in cognitively normal younger and older carriers. We chose to evaluate medial temporal lobe (MTL) activation during encoding and recognition using a perspective-dependent (route or survey) visuospatial memory task by monitoring the blood-oxygen-level-dependent (BOLD) fMRI response in older, non-demented APOE*4 carriers (APOE*4+) and non-carriers (APOE*4-). During encoding, the APOE*4- group had greater average task-associated BOLD responses in ventral visual pathways, including the MTLs, as compared to the APOE*4+ group. Furthermore, MTL activation was greater during route encoding than survey encoding on average in APOE*4-, but not APOE*4+, subjects. During recognition, both groups performed similarly and no BOLD signal differences were found. Finally, within-group analysis revealed MTL activation during encoding was correlated with recognition performance in APOE*4-, but not APOE*4+ subjects. Reduced task-associated MTL activation that does not correlate with either visuospatial perspective or task performance suggests that MTL dysregulation occurs prior to clinical symptoms of dementia in APOE*4 carriers.

Path information effects in visual and proprioceptive spatial learning.

Objects in an environment are often encountered sequentially during spatial learning, forming a path along which object locations are experienced. The present study investigated the effect of spatial information conveyed through the path in visual and proprioceptive learning of a room-sized spatial layout, exploring whether different modalities differentially depend on the integrity of the path. Learning object locations along a coherent path was compared with learning them in a spatially random manner. Path integrity had little effect on visual learning, whereas learning with the coherent path produced better memory performance than random order learning for proprioceptive learning. These results suggest that path information has differential effects in visual and proprioceptive spatial learning, perhaps due to a difference in the way one establishes a reference frame for representing relative locations of objects.

Fixed versus dynamic orientations in environmental learning from ground-level and aerial perspectives.

Ground-level and aerial perspectives in virtual space provide simplified conditions for investigating differences between exploratory navigation and map reading in large-scale environmental learning. General similarities and differences in ground-level and aerial encoding have been identified, but little is known about the specific characteristics that differentiate them. One such characteristic is the need to process orientation; ground-level encoding (and navigation) typically requires dynamic orientations, whereas aerial encoding (and map reading) is typically conducted in a fixed orientation. The present study investigated how this factor affected spatial processing by comparing ground-level and aerial encoding to a hybrid condition: aerial-with-turns. Experiment 1 demonstrated that scene recognition was sensitive to both perspective (ground-level or aerial) and orientation (dynamic or fixed). Experiment 2 investigated brain activation during encoding, revealing regions that were preferentially activated perspective as in previous studies (Shelton and Gabrieli in J Neurosci 22:2711-2717, 2002), but also identifying regions that were preferentially activated as a function of the presence or absence of turns. Together, these results differentiated the behavioral and brain consequences attributable to changes in orientation from those attributable to other characteristics of ground-level and aerial perspectives, providing leverage on how orientation information is processed in everyday spatial learning.

Environmental context influences visually perceived distance.

What properties determine visually perceived space? We discovered that the perceived relative distances of familiar objects in natural settings depended in unexpected ways onthe surrounding visual field. Observers bisected egocentric distances in a lobby, in a hallway, and on an open lawn. Three key findings were the following: (1) Perceived midpoints were too far from the observer, which is the opposite of the common foreshortening effect. (2) This antiforeshortening constant error depended on the environmental setting--greatest in the lobby and hall but nonsignificant on the lawn. (3) Context also affected distance discrimination; variability was greater in the hall than in the lobby or on the lawn. A second experiment replicated these findings, using a method of constant stimuli. Evidently, both the accuracy and the precision of perceived distance depend on subtle properties of the surrounding environment.