Sex difference in cue strategy in a modified version of the Morris water task: correlations between brain and behaviour.

BACKGROUND: Sex differences in spatial memory function have been reported with mixed results in the literature, with some studies showing male advantages and others showing no differences. When considering estrus cycle in females, results are mixed at to whether high or low circulating estradiol results in an advantage in spatial navigation tasks. Research involving humans and rodents has demonstrated males preferentially employ Euclidean strategies and utilize geometric cues in order to spatially navigate, whereas females employ landmark strategies and cues in order to spatially navigate. METHODOLOGY/PRINCIPAL FINDINGS: This study used the water-based snowcone maze in order to assess male and female preference for landmark or geometric cues, with specific emphasis placed on the effects of estrus cycle phase for female rat. Performance and preference for the geometric cue was examined in relation to total hippocampal and hippocampal subregions (CA1&2, CA3 and dentate gyrus) volumes and entorhinal cortex thickness in order to determine the relation between strategy and spatial performance and brain area size. The study revealed that males outperformed females overall during training trials, relied on the geometric cue when the platform was moved and showed significant correlations between entorhinal cortex thickness and spatial memory performance. No gross differences in behavioural performance was observed within females when accounting for cyclicity, and only total hippocampal volume was correlated with performance during the learning trials. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the sex-specific use of cues and brain areas in a spatial learning task.

Enriched childhood experiences moderate age-related motor and cognitive decline.

Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks.

Mental rotational ability is correlated with spatial but not verbal working memory performance and P300 amplitude in males.

This study investigated how both sex and individual differences in a mental rotation test (MRT) influence performance on working memory (WM). To identify the neural substrate supporting these differences, brain electrical activity was measured using the event-related potential technique. No significant sex differences were observed in a test of verbal WM, however males were significantly faster than females to respond to probe stimuli in a test of spatial WM. This difference was no longer significant after controlling for differences in MRT score, suggesting that rotational ability mediates performance in the spatial memory task for both sexes. A posterior P300 was observed in both tasks as participants encoded information into memory, however the amplitude of the P300 correlated with RT in the spatial task but not in the verbal task. Individual differences in the MRT also correlated with RT and with the amplitude of the P300, but again only in the spatial task. After splitting the analysis by sex, partial correlations controlling for MRT revealed that for males, individual differences in rotational ability completely mediated the correlation between the P300 and RT in the spatial task. This mediating effect was not observed for the female participants. The results therefore suggest a relatively stronger association in males between innate mental rotational ability, spatial memory performance, and brain electrophysiological processes supporting spatial memory.

Seasonal and sex differences in the hippocampus of a wild rodent.

Studies across and within species suggest that hippocampus size is sexually dimorphic in polygamous species, but not in monogamous species. Although hippocampal volume varies with sex, season and mating system, few studies have simultaneously tested for sex and seasonal differences. Here, we test for sex and seasonal differences in the hippocampal volume of wild Richardson's ground squirrels (Urocitellus richardsonii), a polygamous species that lives in matrilineal, kin-based social groups and has profound sex differences in behavior. Based on the behavior and ecology of this species, we predicted that males would have a significantly larger hippocampus than females and that the hippocampus would be largest in males during the breeding season. Analyses of both absolute and relative volumes of the hippocampus yielded a significant difference between the sexes and seasons as well as an interaction between the two such that non-breeding males have significantly larger hippocampal volumes than breeding males or females from either season. Dentate gyrus, CA1 and CA3 subfield volumes were generally larger in the non-breeding season and in males, but no significant interaction effects were detected. This sex and seasonal variation in hippocampal volume is likely the result of their social organization and male-only food caching behavior during the non-breeding season. The demonstration of a sex and seasonal variation in hippocampal volume suggests that Richardson's ground squirrel may be a useful model for understanding hippocampal plasticity within a natural context.

Hummingbirds have a greatly enlarged hippocampal formation.

Both field and laboratory studies demonstrate that hummingbirds (Apodiformes, Trochilidae) have exceptional spatial memory. The complexity of spatial-temporal information that hummingbirds must retain and use daily is probably subserved by the hippocampal formation (HF), and therefore, hummingbirds should have a greatly expanded HF. Here, we compare the relative size of the HF in several hummingbird species with that of other birds. Our analyses reveal that the HF in hummingbirds is significantly larger, relative to telencephalic volume, than any bird examined to date. When expressed as a percentage of telencephalic volume, the hummingbird HF is two to five times larger than that of caching and non-caching songbirds, seabirds and woodpeckers. This HF expansion in hummingbirds probably underlies their ability to remember the location, distribution and nectar content of flowers, but more detailed analyses are required to determine the extent to which this arises from an expansion of HF or a decrease in size of other brain regions.

Housing environment and sex affect behavioral recovery from ischemic brain damage.

In previous work from our laboratory, we have developed a model of stroke that allows the comparison of stroke injury across age groups (10-day old, 63-day old, 180-day old rats). In this current study, we incorporated environmental enrichment to determine whether this form of rehabilitation alters behavioral recovery, and whether age and/or sex interacts with enrichment. Our results indicated that ischemic male rats that were housed in standard cages (shoebox housed) performed the poorest on two tasks of motor ability, and that this performance was related to the size of the lesion. With the exception of lesion size, in which 10-day old enriched rats had significantly smaller lesions than either the enriched 63-day old rats or the 180-day old rats, we observed no significant effects of age on behavioral recovery. Thus, our results are consistent with the observation that male rats may be more vulnerable to stroke and that they may differentially benefit from enrichment.

Drive for muscularity, body comparison, and social physique anxiety in men and women.

The presented study tested a model of the relationship between the drive for muscularity (DM), three aspects of body comparison (general, weight-, and muscle-related), and social physique anxiety in college men and women. The findings demonstrated that those with higher levels of DM engaged in more frequent body-related comparisons in all three areas. Greater frequency of both Weight- and Muscle-Related Body Comparison was then predictive of higher levels of social physique anxiety. Constraints placed on the path coefficients showed that the association between DM and Muscle-Related Comparisons was significantly stronger than the association between DM and Weight-Related Comparisons. The model was similar for both genders. The results from the structural models were discussed in terms of Cash's (2002) cognitive-behavioral model of body image and the dual pathway model of boys' and men's body image (Jones & Crawford, 2005).

Hypoxia ischemia affects ultrasonic vocalization in the neonatal rat.

Perinatal hypoxic-ischemic encephalopathy results in a spectrum of pathologies related to the degree of initial infarct and environmental factors, including maternal interactions. Infants actively influence their environment by crying; rat pups produce ultrasonic vocalizations (USVs). Our study observed that ischemic pups engage in less time producing USVs and make fewer USVs overall, with male ischemic pups experiencing reductions in more categories than females. Future studies should consider whether alterations in mother-pup interactions result from these reductions.

Can a reward-based behavioural test be used to investigate the effect of protein-energy malnutrition on hippocampal function?

Our laboratory is investigating the effects of protein-energy malnutrition (PEM) on cognitive outcome following global ischemia. Here, we investigated whether PEM independently impairs working memory in the T-maze and if the associated food reward reverses PEM. Gerbils were fed 12.5% (control diet) or 2% protein. A loss of body weight (20.1%) in the 2% protein group and decreased food intake and serum albumin concentration compared to controls (17.5% and 18.2%, respectively) indicated that PEM was achieved. Based on T-maze criterion frequently used in ischemia studies, no difference was observed in the mean (+/- SEM) number of trials required (control 5.2 +/- 0.7; PEM 4.9 +/- 0.4; p = 0.758) or the number of animals reaching criterion (control 10/12; PEM 12/12; p = 0.140). Using more stringent criterion, PEM animals required fewer trials (control 7.3 +/- 0.7; PEM 5.4 +/- 0.4; p = 0.035), and more reached criterion (control 8/12; PEM 12/12; p = 0.028). PEM may increase motivation to obtain a food reward.

Enriched environment and the effect of age on ischemic brain damage.

Stroke affects all age groups from the newborn to the elderly. Previous work from our laboratory has shown that despite a greater susceptibility to brain damage, the immature brain recovers more rapidly and to a greater extent than does the more mature nervous system. In the current study, we examined the influence of environmental enrichment on the effects of age on the brain damaging effects of stroke. Rats aged 10, 63, and 180 days received ischemic insults following stereotactic intra-cerebral injection of endothelin-1, and resulting in injury to the right middle cerebral artery territory. Rats were then housed in either environmentally enriched cages, or standard cages for 60 days, after which they were sacrificed, and brain volumes determined for the extent of neurologic injury. Rats receiving the insult at 10 days of age showed a reduction of pathologic injury when housed in the enriched cages compared to standard. Conversely, rats receiving the insult at 180 days and housed environmentally enriched cages actually showed an increased volume of brain damage compared to controls. Our findings clearly indicate the dramatic influence of age on the extent of stroke and the influence of rehabilitative therapies. Behavioral correlation to morphologic alterations is required. Attempts at therapeutic interventions clearly need to be age-specific.

Evidence for the influence of testosterone in the performance of spatial navigation in a virtual water maze in women but not in men.

Testosterone (T) may be associated with enhanced spatial navigation in a number of rodent species, although the nature of the relation is equivocal. Similarly, numerous studies in humans generally have found that T is associated with enhanced spatial ability on a variety of paper and pencil tasks that may relate to navigational ability. However, relatively few studies have reported effects of T on navigational ability in humans. We investigated the relationship between endogenous T and performance on a virtual water maze (vWM) and mental rotations test (MROT). ELISA for T was performed on salivary samples that were obtained from participants before and after completion of both spatial tasks. Results indicated that women with low T required more time to locate the hidden platform in the vWM than either group of men or women with high T. Significant negative correlations were found for the entire sample between vWM performance and T, and between vWM latency to escape and MROT. Similar significant correlations were found in women but not men. Thus, our data support the position that T improves performance in the vWM in a linear fashion, most strongly in women. However, further work is needed to confirm this hypothesis in humans.

The influence of aging on recovery following ischemic brain damage.

Stroke is a health hazard that affects all age groups, however the impact of age on brain injury following ischemia remains largely unexamined. We examined the extent to which age, from the newborn to mature adult, affects behavioral recovery following similar degrees of ischemic brain damage. We utilized a model that produces comparable volumes of brain damage between the different ages. Endothelin-1, a potent vasoconstrictor, was injected into the brain of 10, 63 and 180-day-old rats, at the level of the right middle cerebral artery. On days 3, 7, 14, 28 and 56 post-insult, behavioral tests including rota-rod, foot-fault, open-field, inclined screen, tape-removal test and postural reflex were performed. Control animals underwent sham surgery, but ischemia was not induced. Neuropathology was assessed on day 63 post-insult. Volume of damage was determined for each brain as a percentage of the contralateral hemisphere (which remains undamaged). Our results indicated that the volume of damage for each age group was 22.97, 19.97, and 18.85% for 10, 63 and 180-day-old rats, respectively, and were not significantly different from each other. Overall, ischemic animals did significantly more poorly on behavioral testing than did controls. When broken down by age, the difference between ischemics and controls was only evident in the 63 and 180-day-old animals. The tape-removal test revealed main effects of age, group, and day (p<0.001). In addition, significant interactions were noted for day of testing by age (p<0.001), day of testing by group with ischemics performing more slowly than controls, and an age by group interaction which indicated that the 63 and 180-day-old ischemic rats did not recover completely during the testing period and remained significantly slower than their controls (p<0.001). In the foot-fault task, the 63 and 180-day-old ischemic animals performed significantly more poorly on days 3, 7, and 14 of recovery, returning to control values by day 28. The 180-day olds performed more poorly on day 3 of recovery, but then returned to control values. For open-field testing, the results indicate an overall difference between ischemics and controls, with the 63 and 180-day-old animals improving with time though they did not achieve control values. In conclusion our data suggest functional performance is poorly and inconsistently correlated with the extent of morphologic injury across all age groups. The immature rat clearly recovers more completely and more rapidly than do older, more mature rats. The findings may imply a greater degree of brain plasticity in the infant rat compared to the adult, and have important implications related to the underlying mechanisms of recovery and the association between brain damage and functional improvement.

Photographer preference or image purpose? An investigation of posing bias in mammalian and non-mammalian species.

Portraits of human adults typically exhibit leftward biases--that is, they depict individuals with their left cheek prominently featured. The purpose of this study was to determine if photographs of human infants and photographs of non-human animals also display these leftward biases. We observed significant leftward biases in photographs of infants and non-human animals. The only exception to this was a rightward bias observed for photographs of non-mammalian species that were found on personal websites. As the species sampled were likely unaware of the purpose of the photographs, our data are consistent with the interpretation that these biases reflect the preference of the photographer.

When advertising turns "cheeky"!

Portraits typically exhibit leftward posing biases, with people showing more of their left cheek than their right. The current study investigated posing biases in print advertising to determine whether the product advertised affects the posing bias. As the posing bias may be decreasing over time, we also investigated changes in posing biases over a span of more than 100 years. The current investigation coded 2664 advertisements from two time periods; advertisements were coded for target group of advertisement (men, women, both) and posing bias (rightward, leftward, or central). Unlike other studies that typically observe a leftward posing bias, print advertisements exhibit a rightward posing bias, regardless of time-frame. Thus, print advertisements differ greatly from portraits, which may relate to the purpose of advertisements and the role of attractiveness in advertising.

Men are more accurate than women in aiming at targets in both near space and extrapersonal space.

Men excel at motor tasks requiring aiming accuracy whereas women excel at different tasks requiring fine motor skill. However, these tasks are confounded with proximity to the body, as fine motor tasks are performed proximally and aiming tasks are directed at distal targets. As such, it is not known whether the male advantage on tasks requiring aiming accuracy is because men have better aim or is better in the proximal domain in which the task is usually presented. 18 men (M age = 20.6 yr., SD = 3.0) and 20 women (M age = 18.7 yr., SD = 0.9) performed 2 tasks of extrapersonal aiming accuracy (>2 m away), 2 tasks of aiming accuracy performed in near space (< 1 m from them), and a task of fine motor skill. Men outperformed women on both the extrapersonal aiming tasks, and women outperformed men on the task of fine motor skill. However, a male advantage was observed for one of the aiming tasks performed in near space, suggesting that the male advantage for aiming accuracy does not result from proximity.

Rightward biases in free-viewing visual bisection tasks: implications for leftward responses biases on similar tasks.

Neurologically normal individuals exhibit strong leftward response biases during free-viewing perceptual judgments of brightness, quantity, and size. When participants view two mirror-reversed objects and they are forced to choose which object appears darker, more numerous, or larger, the stimulus with the relevant feature on the left side is chosen 60-75% of the time. This effect could be influenced by inaccurate judgments of the true centre-point of the objects being compared. In order to test this possibility, 10 participants completed three visual bisection tasks on stimuli known to elicit strong leftward response biases. Participants were monitored using a remote eye-tracking device and instructed to stare at the subjective midpoint of objects presented on a computer screen. Although it was predicted that bisection errors would deviate to the left of centre (as is the case in the line bisection literature), the opposite effect was found. Significant rightward bisection errors were evident on two of the three tasks, and the leftward biases seen during forced-choice tasks could be the result of misjudgments to the right of centre on these same tasks.

Protein-energy malnutrition impairs functional outcome in global ischemia.

We investigated whether protein-energy malnutrition (PEM) exacerbates brain injury in global ischemia. It was hypothesized that PEM would increase secondary brain damage by worsening ischemia-induced depletion of glutathione (GSH) and increasing oxidative stress. Adult male gerbils were fed an adequate protein (12.5%; C) or low protein (2%; PEM) diet for 4 weeks and subjected to 5 min of bilateral carotid artery occlusion (Ischemia) or sham surgery (Sham). At 12 h post-ischemia, GSH and markers of oxidative stress were measured in hippocampus and neocortex. The remaining gerbils were tested in the open field on days 3, 7, and 10, with viable hippocampal CA1 neurons assessed on day 10. Although the habituation of C-Ischemia gerbils in the open field was normal by day 7, PEM-Ischemia gerbils failed to habituate even by day 10 and spent greater time in the outer zone (P < 0.05). Mean (+/-SEM) total number of viable CA1 neurons at 10 days post-ischemia were C-Sham = 713 (13), C-Ischemia = 264 (48), PEM-Sham = 716 (12), and PEM-Ischemia = 286 (66). Although PEM did not increase CA1 neuron loss caused by ischemia, a subset (4/12) of PEM-Ischemia gerbils showed dramatic reactive gliosis accompanied by extensive neuronal loss. Hippocampal protein thiols were decreased by PEM and ischemia. Although the mechanism is yet to be established, the finding that PEM worsens functional outcome following global ischemia is clinically relevant since 16% of elderly are nutritionally compromised at the time of admission for stroke.

A new model for determining the influence of age and sex on functional recovery following hypoxic-ischemic brain damage.

Stroke is a disorder affecting the lives of all age groups, and particularly those at the opposite ends of the age spectrum. It is generally believed that the immature brain is more resistant to damage resulting from a hypoxic/ischemic injury, and that it is also more 'plastic' in terms of its ability to recover. Evidence from our laboratory, and a host of others, has indicated, however, that the developing brain may in fact be more sensitive to injury resulting from hypoxia-ischemia. The question remains, however, whether the immature brain has a greater capacity for recovery. In order to determine the relative capability for functional recovery between age groups, a stroke model of comparable injury is required. This paper describes a new rodent model of ischemic injury allowing for comparisons of behavioral recovery spanning the spectrum of ages between newborn and the elderly. Endothelin-1, a potent vasoconstrictor, was stereotactically injected into the brains of 10-, 63-, and 180-day-old Wistar rats, immediately adjacent to the middle cerebral artery. Regionally, the cortex, caudate, and thalamus were most significantly affected, with sparing of the hippocampus. Pathologic assessment indicated a similar degree of injury across age groups affecting the territorial distribution of the middle cerebral artery, with a predominance of damage in the anterior sections of the cortex and caudate (p < 0.05), compared to the posterior sections including the cortex and thalamus. There were no regional differences in the extent of damage between age groups. Interestingly, however, there were significant differences between males and females regarding the overall extent of brain damage (p < 0.05), with males showing greater damage than females. In addition, there were significant regional differences in the extent of damage between males and females, particularly regarding cortical damage (p < 0.05), both anteriorly and posteriorly, and the caudate anteriorly (p < 0.05). Our findings provide an important new model for comparison of brain damage among the entire spectrum of ages affected by stroke. Importantly, this will allow for further investigations regarding both functional recovery and gender difference comparisons. This may have important ramifications for the development of therapeutic interventions that are age and gender specific.

Involvement of extracellular regulated kinase and p38 kinase in hippocampal seizure tolerance.

The mechanisms underlying brain seizure tolerance, a phenomenon in which brief periods of seizures protect brain against the lethal effects of subsequent sustained seizures, are poorly understood. Because brain seizure tolerance and brain ischemia tolerance likely share certain common mechanisms, the recent evidence that activation of extracellular regulated kinase (ERK) and p38 kinase pathways plays a critical role in ischemic preconditioning suggests that a similar mechanism may underlie brain seizure tolerance. We investigated the hypothesis in a rat kainic acid preparation of seizure preconditioning and tolerance, which was established by induction of one episode of priming epileptic status lasting for 20 min on the first day and another episode of sustained epileptic status lasting for 2 hr on the second day. We observed that acute seizures lead to a rapid activation of ERK and p38 in the hippocampal CA3 area, the brain region most susceptible to the lethal effects of epileptic status. Pretreatment with the ERK inhibitor PD98059 and the p38 inhibitor SB203580 selectively reduces seizure-elicited activation of ERK and p38, respectively, and significantly reduces priming seizure-induced protection of CA3 neurons. These findings indicate that, similar to brain ischemia tolerance, brain seizure tolerance also involves the ERK and p38 signaling pathways.

Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid.

PURPOSE: The purpose of this study was to determine whether N-palmitoylethanolamide (PEA), a putative endocannabinoid, would be effective against kindled amygdaloid seizures. For a comparison with earlier work, we also tested the effectiveness of PEA against pentylenetetrazol (PTZ)-induced convulsions. METHODS: Kindling electrodes were implanted bilaterally in the amygdala in 32 Long-Evans rats. After the kindling of generalized (stage 5) seizures, the effects of PEA administration [i.p.; 1, 10, 100 mg/kg in dimethylsulfoxide (DMSO)] were evaluated for anticonvulsant activity. PEA (40 mg/kg, i.p. in DMSO) also was tested for anticonvulsant activity against PTZ-induced convulsions (75 mg/kg, i.p.). RESULTS: After i.p. administration of PEA, kindled rats displayed an increased latency to clonus at the 1-mg/kg dose. No other dose-dependent effects were noted. When tested against PTZ-induced convulsions, PEA protected against tonic convulsions and prolonged the latency between convulsive episodes. CONCLUSIONS: PEA produces antiepileptic effects, but does not completely suppress seizures. The mechanism of action of PEA remains to be defined.