Epigenetics in the mature mammalian brain: effects on behavior and synaptic transmission

The role of epigenetic mechanisms in control of gene expression during mammalian development is well established. Associations between specific DNA or histone modifications and numerous neurodevelopmental and neurodegenerative disorders implies significant consequences of epigenetic dysregulation in both the developing and mature brain, the latter of which is the general focus of this review. Accumulating evidence suggests that epigenetic changes are involved in normal cognitive processes in addition to neurological and psychiatric disorders. Recent investigations into the regulation of epigenetic modifications in the adult brain have revealed novel and surprisingly dynamic mechanisms for controlling learning and memory-related behaviors as well as long-term synaptic plasticity. DNA methylation and histone acetylation have also been implicated in the modulation of basal synaptic transmission and the balance between excitation and inhibition in various brain regions. Studies have begun to uncover some of the alterations in gene expression that appear to mediate many of these effects, but an understanding of the precise mechanisms involved is still lacking. Nevertheless, the fundamental importance of epigenetic processes in influencing neuronal activity is becoming increasingly evident.     

Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment

Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models--from repeated and chronic ethanol exposure to thiamine deficiency--is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone.     

Does reflection lead to wise choices?

Does conscious reflection lead to good decision-making? Whereas engaging in reflection is traditionally thought to be the best way to make wise choices, recent psychological evidence undermines the role of reflection in lay and expert judgement. The literature suggests that thinking about reasons does not improve the choices people make, and that experts do not engage in reflection, but base their judgements on intuition, often shaped by extensive previous experience. Can we square the traditional accounts of wisdom with the results of these empirical studies? Should we even attempt to? I shall defend the view that philosophy and cognitive sciences genuinely interact in tackling questions such as whether reflection leads to making wise choices.     

The effects of "thin ideal" media on women's body image concerns and eating-related intentions: the beneficial role of an autonomous regulation of eating behaviors

The present study examines the protective role of an autonomous regulation of eating behaviors (AREB) on the relationship between trait body dissatisfaction and women's body image concerns and eating-related intentions in response to “thin ideal” media. Undergraduate women (n = 138) were randomly assigned to view a “thin ideal” video or a neutral video. As hypothesized, trait body dissatisfaction predicted more negative affect and size dissatisfaction following exposure to the “thin ideal” video among women who displayed less AREB. Conversely, trait body dissatisfaction predicted greater intentions to monitor food intake and limit unhealthy foods following exposure to the “thin ideal” video among women who displayed more AREB.     

Accuracy in estimating the body weight of self and others: Impact of dietary restraint and BMI

We examined the accuracy of people's estimates of their own body weight and of the body weight of other people. Female undergraduates (n = 132) self-reported their weight, were weighed by the experimenter, and completed a measure of dietary restraint. Participants also viewed 10 photographs of women ranging from underweight to obese and estimated their body weight. Individuals high in dietary restraint underestimated their own weight to a greater extent than those low in dietary restraint, but this effect was accounted for by individual differences in BMI: heavier participants underestimated their weight to a greater extent than leaner participants. Participants also underestimated the weight of heavier targets to a greater extent than they did leaner targets, but the degree of inaccuracy was not related to participants’ dietary restraint or BMI. These findings support the hypothesis that inaccuracies in self-reported weight reflect deliberate misreporting rather than a cognitive or perceptual bias.     

Holding a manual response sequence in memory can disrupt vocal responses that share semantic features with the manual response

Holding an action plan in memory for later execution can delay execution of another action if the actions share a similar (compatible) feature. This compatibility interference (CI) occurs for actions that share the same response modality (e.g., manual response). We investigated whether CI can generalize to actions that utilize different response modalities (manual and vocal). In three experiments, participants planned and withheld a sequence of key-presses with the left- or right-hand based on the visual identity of the first stimulus, and then immediately executed a speeded, vocal response (‘left’ or ‘right’) to a second visual stimulus. The vocal response was based on discriminating stimulus color (Experiment 1), reading a written word (Experiment 2), or reporting the antonym of a written word (Experiment 3). Results showed that CI occurred when the manual response hand (e.g., left) was compatible with the identity of the vocal response (e.g., ‘left’) in Experiment 1 and 3, but not in Experiment 2. This suggests that partial overlap of semantic codes is sufficient to obtain CI unless the intervening action can be accessed automatically (Experiment 2). These findings are consistent with the code occupation hypothesis and the general framework of the theory of event coding (Behav Brain Sci 24:849–878, 2001a; Behav Brain Sci 24:910–937, 2001b).     

Learn locally, think globally. Exemplar variability supports higher-order generalization and word learning

Research suggests that variability of exemplars supports successful object categorization; however, the scope of variability's support at the level of higher-order generalization remains unexplored. Using a longitudinal study, we examined the role of exemplar variability in first- and second-order generalization in the context of nominal-category learning at an early age. Sixteen 18-month-old children were taught 12 categories. Half of the children were taught with sets of highly similar exemplars; the other half were taught with sets of dissimilar, variable exemplars. Participants' learning and generalization of trained labels and their development of more general word-learning biases were tested. All children were found to have learned labels for trained exemplars, but children trained with variable exemplars generalized to novel exemplars of these categories, developed a discriminating word-learning bias generalizing labels of novel solid objects by shape and labels of nonsolid objects by material, and accelerated in vocabulary acquisition. These findings demonstrate that object variability leads to better abstraction of individual and global category organization, which increases learning outside the laboratory.     

Memory for reward location is enhanced even though acetylcholine efflux within the amygdala is impaired in rats with damage to the diencephalon produced by thiamine deficiency

Sleep facilitates declarative memory processing. However, we know little about whether sleep plays a role in the processing of a fundamental feature of declarative memory, relational memory – the flexible representation of items not directly learned prior to sleep. Thirty-one healthy participants first learned at 12 pm two sets of face–object photograph pairs (direct associative memory), in which the objects in each pair were common to both lists, but paired with two different faces. Participants either were given approximately 90 min to have a NREM-only daytime nap (n = 14) or an equivalent waking period (n = 17). At 4:30 pm, participants who napped demonstrated significantly better retention of direct associative memory, as well as better performance on a surprise task assessing their relational memory, in which participants had to associate the two faces previously paired with the same object during learning. Particularly noteworthy, relational memory performance was correlated with the amount of NREM sleep during the nap, with only slow-wave sleep predicting relational memory performance. Sleep stage data did not correlate with direct associative memory retention. These results suggest an active role for sleep in facilitating multiple processes that are not limited to the mere strengthening of rote memories, but also the binding of items that were not directly learned together, reorganizing them for flexible use at a later time.     

Data Management in Academic Settings: An Intellectual Property Perspective

Intellectual property can be an important asset for academic institutions. Good data management practices are important for capture, development and protection of intellectual property assets. Selected issues focused on the relationship between data management and intellectual property are reviewed and a thesis that academic institutions and scientists should honor their obligations to responsibly manage data.