Abnormal EEG signal energy in the elderly: A wavelet analysis of event-related potentials during a stroop task.

BACKGROUND: Previous work showed that elderly with excess in theta activity in their resting state electroencephalogram (EEG) are at higher risk of cognitive decline than those with a normal EEG. By using event-related potentials (ERP) during a counting Stroop task, our prior work showed that elderly with theta excess have a large P300 component compared with normal EEG group. This increased activity could be related to a higher EEG signal energy used during this task. NEW METHOD: By wavelet analysis applied to ERP obtained during a counting Stroop task we quantified the energy in the different frequency bands of a group of elderly with altered EEG. RESULTS: In theta and alpha bands, the total energy was higher in elderly subjects with theta excess, specifically in the stimulus categorization window (258-516 ms). Both groups solved the task with similar efficiency. COMPARISON WITH EXISTING METHODS: The traditional ERP analysis in elderly compares voltage among conditions and groups for a given time window, while the frequency composition is not usually examined. We complemented our previous ERP analysis using a wavelet methodology. Furthermore, we showed the advantages of wavelet analysis over Short Time Fourier Transform when exploring EEG signal during this task. CONCLUSIONS: The higher EEG signal energy in ERP might reflect undergoing neurobiological mechanisms that allow the elderly with theta excess to cope with the cognitive task with similar behavioral results as the normal EEG group. This increased energy could promote a metabolic and cellular dysregulation causing a greater decline in cognitive function.

Experience-Regulated Neuronal Signaling in Maternal Behavior.

Maternal behavior is shaped and challenged by the changing developmental needs of offspring and a broad range of environmental factors, with evidence indicating that the maternal brain exhibits a high degree of plasticity. This plasticity is displayed within cellular and molecular systems, including both intra- and intercellular signaling processes as well as transcriptional profiles. This experience-associated plasticity may have significant overlap with the mechanisms controlling memory processes, in particular those that are activity-dependent. While a significant body of work has identified various molecules and intracellular processes regulating maternal care, the role of activity- and experience-dependent processes remains unclear. We discuss recent progress in studying activity-dependent changes occurring at the synapse, in the nucleus, and during the transport between these two structures in relation to maternal behavior. Several pre- and postsynaptic molecules as well as transcription factors have been found to be critical in these processes. This role reflects the principal importance of the molecular and cellular mechanisms of memory formation to maternal and other behavioral adaptations.

Imbalance in cerebral protein homeostasis: Effects on memory consolidation.

The long-standing hypothesis that memory consolidation is dependent upon de novo protein synthesis is based primarily on the amnestic effects of systemic administration of protein synthesis inhibitors (PSIs). Early experiments on mice showed that PSIs produced interference with memory consolidation that was dependent on the doses of PSIs, on the interval between drug injection and training, and, importantly, on the degree and duration of protein synthesis inhibition in the brain. Surprisingly, there is a conspicuous lack of information regarding the relationship between the duration of protein synthesis inhibition produced by PSIs and memory consolidation in the rat, one of the species most widely used to study memory processes. We found that, in the male rat, a single injection of cycloheximide, a commonly used PSI, produced a significant imbalance in protein homeostasis: an early inhibition of protein synthesis that lasted for at least one hour, followed by hyperproduction of proteins that lasted three days. We evaluated memory consolidation of inhibitory avoidance trained with either low or high intensity of foot-shock at the peaks of protein synthesis inhibition and protein hyperproduction. We found that, independent of the moment of training, the low-foot-shock groups showed amnesia, while the high-foot-shock groups displayed optimal memory performance. These results indicate that memory consolidation of relatively weak training is impaired by the inhibition or hyperproduction of protein synthesis, and that intense training overcomes this dysregulation of protein homeostasis allowing for memory formation probably through non-genomic mechanisms.

Retrieval of Inhibitory Avoidance Memory Induces Differential Transcription of arc in Striatum, Hippocampus, and Amygdala.

Similar to the hippocampus and amygdala, the dorsal striatum is involved in memory retrieval of inhibitory avoidance, a task commonly used to study memory processes. It has been reported that memory retrieval of fear conditioning regulates gene expression of arc and zif268 in the amygdala and the hippocampus, and it is surprising that only limited effort has been made to study the molecular events caused by retrieval in the striatum. To further explore the involvement of immediate early genes in retrieval, we used real-time PCR to analyze arc and zif268 transcription in dorsal striatum, dorsal hippocampus, and amygdala at different time intervals after retrieval of step-through inhibitory avoidance memory. We found that arc expression in the striatum increased 30 min after retrieval while no changes were observed in zif268 in this region. Expression of arc and zif268 also increased in the dorsal hippocampus but the changes were attributed to context re-exposure. Control procedures indicated that in the amygdala, arc and zif268 expression was not dependent on retrieval. Our data indicate that memory retrieval of inhibitory avoidance induces arc gene expression in the dorsal striatum, caused, very likely, by the instrumental component of the task. Striatal arc expression after retrieval may induce structural and functional changes in the neurons involved in this process.

Two Different Populations within the Healthy Elderly: Lack of Conflict Detection in Those at Risk of Cognitive Decline.

During healthy aging, inhibitory processing is affected at the sensorial, perceptual, and cognitive levels. The assessment of event-related potentials (ERPs) during the Stroop task has been used to study age-related decline in the efficiency of inhibitory processes. Studies using ERPs have found that the P300 amplitude increases and the N500 amplitude is attenuated in healthy elderly adults compared to those in young adults. On the other hand, it has been reported that theta excess in resting EEG with eyes closed is a good predictor of cognitive decline during aging 7 years later, while a normal EEG increases the probability of not developing cognitive decline. The behavioral and ERP responses during a Counting-Stroop task were compared between 22 healthy elderly subjects with normal EEG (Normal-EEG group) and 22 healthy elderly subjects with an excess of EEG theta activity (Theta-EEG group). Behaviorally, the Normal-EEG group showed a higher behavioral interference effect than the Theta-EEG group. ERP patterns were different between the groups, and two facts are highlighted: (a) the P300 amplitude was higher in the Theta-EEG group, with both groups showing a P300 effect in almost all electrodes, and (b) the Theta-EEG group did not show an N500 effect. These results suggest that the diminishment in inhibitory control observed in the Theta-EEG group may be compensated by different processes in earlier stages, which would allow them to perform the task with similar efficiency to that of participants with a normal EEG. This study is the first to show that healthy elderly subjects with an excess of theta EEG activity not only are at risk of developing cognitive decline but already have a cognitive impairment.

Protein synthesis is not required for acquisition, consolidation, and extinction of high foot-shock active avoidance training.

Long-term memory of active avoidance in mice is not disturbed by administration of protein synthesis inhibitors (PSIs) when relatively high levels of training are used, whereas a detrimental effect is produced with lower levels of training. PSIs also disrupt extinction of avoidance behaviors in rodents, but it is not clear whether PSIs also affect this form of learning when the behavior to be extinguished was produced by a high level of training. Experiment 1 demonstrated that rats treated with the PSI cycloheximide (CXM) 30 min before training developed normal acquisition after training with either high or low foot-shock stimulation, but that memory consolidation was hindered only after low foot-shock training. Experiment 2 demonstrated that CXM disrupted extinction when administered before the first of a series of extinction sessions when low foot-shock intensity was used during training; in contrast, after training with a higher foot-shock, the PSI treatment only interfered transiently with extinction. These results indicate that acquisition, consolidation, and extinction of active avoidance learning produced by high aversive stimulation are not dependent on protein synthesis and that these processes are governed by mechanisms different from those underlying moderate forms of learning.