Increased stress-induced intra-hippocampus corticosterone rise associated with memory impairments in middle-aged mice

The present study investigates the relationships between hippocampal corticosterone concentrations and memory retrieval performance in stress and non-stress conditions, in both young (6 month-old) and middle-aged (16 month-old) mice. For this purpose, the time-course evolution of stress-induced corticosterone rise in the dorsal hippocampus (dHPC) was investigated in both young and middle-aged mice. In parallel, the evolution of memory retrieval patterns was assessed using a contextual serial discrimination task (CSD). Finally, metyrapone (corticosterone synthesis inhibitor) was administered in order to evaluate the stress-induced impact of corticosterone rise on contextual memory retrieval in middle-aged animals.Results showed that: (i) non-stressed middle-aged mice exhibited a memory retrieval pattern opposite to that of non-stressed young animals, but similar to that of stressed young mice; (ii) the impact of stress on memory performance was transient (90 min) in young, as compared to middle-aged mice (120 min); (iii) dHPC basal (non-stress) corticosterone level was significantly increased by ageing; (iv) acute stress induced a rapid (15 min) and transient (90 min) dHPC corticosterone rise in young mice, while exhibiting greater magnitude and duration (120 min) in middle-aged animals; and (v) both the stress-induced endocrinal and memory effects were blocked by metyrapone in young and middle-aged mice.Finally, to our knowledge, the present work is the first study to directly measure the corticosterone rise in the hippocampus following exposure to stress and to directly correlate the corticosterone changes in the hippocampus with memory performance in both young and middle-aged mice.     

Common neuropsychological deficits associated with stroke survivors' impaired performance on a useful field of view test

Useful field of view is a measure of information processing in peripheral vision that has potential for predicting impaired driving performance. The present study was performed to examine whether common neuropsychological deficits resulting from stroke might be associated with useful field of view impairment. 46 stroke survivors had impaired useful field of view test performance when compared to individuals without stroke (t30.6= -4.33, p<.001). The impairments in useful field of view of stroke survivors were associated with impaired peripheral fields, slowed processing speeds, and diminished attention. Such impairment was not localized to lesions in any particular brain area. Results allow the inference that common neuropsychological impairments may have contributed to inefficient extraction of visual information from peripheral vision.     

Reasoning deficits among illicit drug users are associated with aspects of cannabis use

Deficits in deductive reasoning have been observed among ecstasy/polydrug users. The present study seeks to investigate dose-related effects of specific drugs and whether these vary with the cognitive demands of the task. One hundred and five participants (mean age 21.33, SD 3.14; 77 females, 28 males) attempted to generate solutions for eight one-model syllogisms and one syllogism for which there was no valid conclusion. All of the one-model syllogisms generated at least one valid conclusion and six generated two valid conclusions. In these six cases, one of the conclusions was classified as common and the other as non-common. The number of valid common inferences was negatively associated with the aspects of short-term cannabis use and with measures of IQ. The outcomes observed were more than simple post-intoxication effects since cannabis use in the 10 days immediately before testing was unrelated to reasoning performance. Following adjustment for multiple comparisons, the number of non-common valid inferences was not significantly associated with any of the drug-use measures. Recent cannabis use appears to impair the processes associated with generating valid common inferences while not affecting the production of non-common inferences. It is possible, therefore, that the two types of inference may recruit different executive resources, which may differ in their susceptibility to cannabis-related effects.     

Patterns of intellectual ability in children with verbal deficits

Patterns of intellectual ability were examined in 81 children with verbal deficits identified by a Low Verbal/High Performance WISC profile. The results of verbal and nonverbal tests of intellectual functioning were factor-analyzed, and three groups of children were defined based on patterns of factor scores. Group 1 consisted of children with a Specific Language Disability (SLD) but good Abstract Reasoning ability, while Group 2 included SLD children with good Sequencing-Memory skills. Group 3 children displayed a General Language Disability (GLD) with deficits in both abstract reasoning and sequencing memory. The intellectual patterns were related to cognitive interpretations and found to have educational implications, with Group 1 children reading adequately, Group 2 children showing somewhat poorer reading skills, and Group 3 children reading very poorly. These findings emphasize the importance of identifying subgroups of children with verbal deficits and demonstrate the feasibility of extracting relatively specific cognitive information from global measures of intelligence. The results question the appropriateness of applying traditional assumptions regarding cognitive organization derived from studies of normal children to atypical groups of children.     

Memory deficits in young schizophrenics with normal general intellectual function

The aim of the present study was to examine different dimensions of memory functioning in young schizophrenics with normal general intellectual abilities. Thirty-three patients with schizophrenia and 33 healthy controls were included in the study. The results suggest that immediate short-term memory is intact, though there emerged a working memory deficit in the schizophrenia group. Deficient encoding of verbal material was observed in some, but not in other, testing conditions. There also seemed to be a retrieval deficit for verbal material in schizophrenia, though no storage deficit was indicated. Impaired memory for non-verbal material was also revealed. These results occurred in a context of intact executive functioning as measured by the Wisconsin Card Sorting Test. The results indicate that temporal and frontal structures, as well as their interconnections, may be compromised in schizophrenia.     

Impaired long-term potentiation and enhanced neuronal excitability in the amygdala of CaV1.3 knockout mice

Previously, we demonstrated that mice in which the gene for the L-type voltage-gated calcium channel Ca_V1.3 is deleted (Ca_V1.3 knockout mice) exhibit an impaired ability to consolidate contextually-conditioned fear. Given that this form of Pavlovian fear conditioning is critically dependent on the basolateral complex of the amygdala (BLA), we were interested in the mechanisms by which Ca_V1.3 contributes to BLA neurophysiology. In the present study, we used in vitro amygdala slices prepared from Ca_V1.3 knockout mice and wild-type littermates to explore the role of Ca_V1.3 in long-term potentiation (LTP) and intrinsic neuronal excitability in the BLA. We found that LTP in the lateral nucleus (LA) of the BLA, induced by high-frequency stimulation of the external capsule, was significantly reduced in Ca_V1.3 knockout mice. Additionally, we found that BLA principal neurons from Ca_V1.3 knockout mice were hyperexcitable, exhibiting significant increases in firing rates and decreased interspike intervals in response to prolonged somatic depolarization. This aberrant increase in neuronal excitability appears to be at least in part due to a concomitant reduction in the slow component of the post-burst afterhyperpolarization. Together, these results demonstrate altered neuronal function in the BLA of Ca_V1.3 knockout mice which may account for the impaired ability of these mice to consolidate contextually-conditioned fear.     

Memory deficits in early infantile autism: some similarities to the amnesic syndrome.

Autistic children were compared with control children on tasks in which retention was tested by different methods. In three tests of recall, using named pictures, written words and spoken words as test stimuli, autistic children were impaired in comparison with age-matched normal children and with controls matched for verbal ability. In one test of forced-choice recognition of pictures, autistic children were impaired in comparison with ability-matched controls. In three tests of cued recall, using named pictures, written words and spoken words as test stimuli, and acoustic, graphemic and semantic cues, autistic children were not impaired in comparison with normal age-matched controls. In one test of paired-associate learning using non-related word pairs as test stimuli autistic children were not impaired in comparison with normal age-matched controls. These experimental paradigms were similar to some that have been used to investigate the amnesic syndrome in man. Thus findings on paired-associate learning differ in autistic and amnesic subjects, but findings on recall, recognition and cued recall are comparable. A possible parallel between autism and amnesia is discussed.     

Caudate nucleus-dependent response strategies in a virtual navigation task are associated with lower basal cortisol and impaired episodic memory

The present research examined the relationship between endogenous glucocorticoids, navigational strategies in a virtual navigation task, and performance on standard neuropsychological assessments of memory. Healthy young adult participants (N = 66, mean age: 21.7) were tested on the 4 on 8 virtual maze (4/8 VM) and standard neuropsychological tests such as the Rey-Osterrieth Complex Figure (RO) and the Rey Auditory Verbal Learning Task (RAVLT), which measure episodic memory. The 4/8 VM differentiates between navigational strategies, where participants either use a hippocampal-dependent spatial strategy by building relationships between landmarks, or a caudate nucleus-dependent stimulus–response strategy by automatizing a pattern of open and closed arms to learn the location of objects within the maze. Degree of stress was assessed by administering the Perceived Stress Scale (PSS) questionnaire. Cortisol samples were taken on two consecutive days upon waking, 30 min after waking, at 11 am, 4 pm, and 9 pm. There was a significant difference in basal levels of cortisol between spatial and response learners. Interestingly, response learners had significantly lower cortisol levels throughout the day. The two groups did not differ in terms of perceived stress as measured with the PSS questionnaire. Moreover, there was no significant correlation between PSS scores and salivary cortisol levels, indicating that the higher cortisol levels in the spatial group were not associated with greater perceived stress. In addition, participants who spontaneously used a spatial strategy performed significantly better on the RAVLT and RO. These data indicate that the cortisol levels in the spatial group may be optimal in terms of episodic memory performance whereas the cortisol levels in the response group may be associated with poorer memory. These results are suggestive of an inverted U-shaped curve describing the effects of basal levels of circulating cortisol on memory in young adults.     

Sensitivity to stimulus similarity is associated with greater sustained attention ability

Sustained attention is critical for tasks where perceptual information must be continuously processed, like reading or driving; however, the cognitive processes underlying sustained attention remain incompletely characterized. In the experiments that follow, we explore the relationship between sustaining attention and the contents and maintenance of task-relevant features in an attentional template. Specifically, we administered the gradual onset continuous performance task (gradCPT), a sensitive measure of sustained attention, to a large web-based sample (N>20,000) and a smaller laboratory sample for validation and extension. The gradCPT requires participants to respond to most stimuli (city scenes – 90 %) and withhold to rare target images (mountain scenes – 10 %). By using stimulus similarity to probe the representational content of task-relevant features—assuming either exemplar- or category-based feature matching—we predicted that RTs for city stimuli that were more “mountain-like” would be slower and “city-like” mountain stimuli would elicit more erroneous presses. We found that exemplar-based target-nontarget (T-N) similarity predicted both RTs and erroneous button presses, suggesting a stimulus-specific feature matching process was adopted. Importantly, individual differences in the degree of sensitivity to these similarity measures correlated with conventional measures of attentional ability on the gradCPT as well as another CPT that is perceptually less demanding. In other words, individuals with greater sustained attention ability (assessed by two tasks) were more likely to be influenced by stimulus similarity on the gradCPT. These results suggest that sustained attention facilitates the construction and maintenance of an attentional template that is optimal for a given task.     

Age-related deficits in face recognition are related to underlying changes in scanning behavior

Previous studies demonstrating age-related impairments in recognition memory for faces are suggestive of underlying differences in face processing. To study these differences, we monitored eye movements while younger and older adults viewed younger and older faces. Compared to the younger group, older adults showed increased sampling of facial features, and more transitions. However, their scanning behavior was most similar to the younger group when looking at older faces. Moreover, while older adults exhibited worse recognition memory than younger adults overall, their memory was more accurate for older faces. These findings suggest that age-related differences in recognition memory for faces may be related to changes in scanning behavior, and that older adults may use social group status as a compensatory processing strategy.     

Recall and recognition are equally impaired in patients with selective hippocampal damage

In two recent studies, the hypothesis that recall is more severely impaired than recognition in patients with damage thought to be limited to the hippocampus was tested. Yonelinas et al. (2002) reported findings that appeared to support this hypothesis, whereas Manns, Hopkins, Reed, Kitchener, and Squire (2003) found that recall and recognition were equally impaired. An analysis of the individual subject data from the two studies revealed that the apparent disagreement stemmed from the inclusion of a single outlying recognition score for 1 of the 55 control subjects in Yonelinas et al. (2002). When that outlier was excluded, the studies were in agreement that recognition and recall are substantially and similarly impaired in these patients. Yonelinas et al. (2002) also analyzed remember/know judgments and ROC data in an effort to show that recollection is selectively impaired in patients, but these analyses also raise problems.     

Susceptibility to induction of long-term depression is associated with impaired memory in aged Fischer 344 rats

The current study employed aged and young male Fischer 344 rats to examine the relationship between long-term depression (LTD), age, and memory. Memory performance was measured on two tasks that are sensitive to hippocampal function; inhibitory avoidance and spatial discrimination on the Morris water maze. The slope of the extracellular excitatory postsynaptic field potential was recorded from CA3-CA1 synapses in hippocampal slices. Low frequency stimulation (LFS) induced a modest LTD only in aged animals under standard recording conditions. The decrease in synaptic transmission examined only in aged animals correlated with memory scores on the spatial task and LTD was not observed in aged animals with the highest memory scores. LTD induction was facilitated by increasing the Ca(2+)/Mg(2+) ratio of the recording medium or employing a paired-pulse stimulation paradigm. Age differences disappeared when LFS was delivered under conditions of elevated Ca(2+)/Mg(2+) in the recording medium. Using multiple induction episodes under conditions which facilitate LTD-induction, no age-related difference was observed in the maximum level of LTD. The results indicate that the increased susceptibility to LTD induction is associated with impaired memory and results from a shift in the induction process. The possible relationship between LTD and memory function is discussed.     

Age-related memory deficits in rats and mice: enhancement with peripheral injections of epinephrine

Epinephrine peripherally administered to rats and mice immediately following avoidance and/or appetitive training enhances later memory retention in both young and old animals. These findings suggest a possible involvement of peripheral adrenergic systems in memory dysfunctions which accompany aging.     

Psychosocial and socioeconomic factors associated with glycated hemoglobin in nondiabetic middle-aged men and women.

The authors tested associations between glycated hemoglobin (HbA1c; an index of glucose homeostasis and an indicator of cardiovascular disease risk in nondiabetic populations) and socioeconomic status (defined by grade of employment) and psychosocial factors in 234 British civil servants. HbA1c concentration was inversely related to grade of employment. Higher HbA1c was associated with greater waist-hip ratio, lower control at work, lower internal locus of control, lower active coping, and lower social support. Control at work, internal and chance locus of control, and active coping were also related to socioeconomic status. The association of social support but not other psychosocial factors with HbA1c was independent of socioeconomic status. HbA1c may complement measures of the metabolic syndrome and insulin resistance in studies of psychosocial factors in cardiovascular disease risk.     

Enhanced neuronal excitability in rat CA1 pyramidal neurons following trace eyeblink conditioning acquisition is not due to alterations in I M

Previous work done by our laboratory has demonstrated a reduction of the post-burst afterhyperpolarization (AHP) and accommodation following trace eyeblink conditioning in rabbit CA1 pyramidal neurons. Our laboratory has also demonstrated a reduction in the AHP in rat CA1 pyramidal neurons following spatial learning. In the current study we have extended our findings in rabbits by showing a reduction in both the AHP and accommodation in F344 X BN rat CA1 pyramidal neurons following acquisition of trace eyeblink conditioning. A component current of the AHP, I(M), was evaluated with a specific blocker of this current, and showed no apparent contribution to the learning-related increase in neuronal excitability. Rather, a reduction in an isoproterenol-sensitive component of the AHP, presumably sI(AHP), was observed to underlie the learning-specific change.     

The ability to regulate emotion is associated with greater well-being, income, and socioeconomic status

Are people who are best able to implement strategies to regulate their emotional expressive behavior happier and more successful than their counterparts? Although past research has examined individual variation in knowledge of the most effective emotion regulation strategies, little is known about how individual differences in the ability to actually implement these strategies, as assessed objectively in the laboratory, are associated with external criteria. In two studies, we examined how individual variation in the ability to modify emotional expressive behavior in response to evocative stimuli is related to well-being and financial success. Study 1 showed that individuals who can best suppress their emotional reaction to an acoustic startle are happiest with their lives. Study 2 showed that individuals who can best amplify their emotional reaction to a disgust-eliciting movie are happiest with their lives and have the highest disposable income and socioeconomic status. Thus, being able to implement emotion regulation strategies in the laboratory is closely linked to well-being and financial success.