EEG markers of successful allocentric spatial working memory maintenance in humans.

Several brain regions in the frontal, occipital and medial temporal lobes are known to contribute to spatial information processing. In contrast, the oscillatory patterns contributing to allocentric spatial working memory maintenance are poorly understood, especially in humans. Here, we tested twenty-three 21- to 32-year-old and twenty-two 64- to 76-year-old healthy right-handed adults in a real-world, spatial working memory task and recorded electroencephalographic (EEG) activity during the maintenance period. We established criteria for designating recall trials as perfect (no errors) or failed (errors and random search) and identified 8 young and 13 older adults who had at least 1 perfect and 1 failed trial amongst 10 recall trials. Individual alpha frequency-based analyses were used to identify oscillatory patterns during the maintenance period of perfect and failed trials. Spectral scalp topographies showed that individual theta frequency band relative power was stronger in perfect than in failed trials in the frontal midline and posterior regions. Similarly, gamma band (30-40 Hz) relative power was stronger in perfect than in failed trials over the right motor cortex. Exact low-resolution brain electromagnetic tomography in the frequency domain identified greater theta power in perfect than in failed trials in the secondary visual area (BA19) and greater gamma power in perfect than in failed trials in the right supplementary motor area. The findings of this exploratory study suggest that theta oscillations in the occipital lobe and gamma oscillations in the secondary motor cortex (BA6) play a particular role in successful allocentric spatial working memory maintenance.

Age-Related Differences in Resting-State EEG and Allocentric Spatial Working Memory Performance.

During normal aging resting-state brain activity changes and working memory performance declines as compared to young adulthood. Interestingly, previous studies reported that different electroencephalographic (EEG) measures of resting-state brain activity may correlate with working memory performance at different ages. Here, we recorded resting-state EEG activity and tested allocentric spatial working memory in healthy young (20-30 years) and older (65-75 years) adults. We adapted standard EEG methods to record brain activity in mobile participants in a non-shielded environment, in both eyes closed and eyes open conditions. Our study revealed some age-group differences in resting-state brain activity that were consistent with previous results obtained in different recording conditions. We confirmed that age-group differences in resting-state EEG activity depend on the recording conditions and the specific parameters considered. Nevertheless, lower theta-band and alpha-band frequencies and absolute powers, and higher beta-band and gamma-band relative powers were overall observed in healthy older adults, as compared to healthy young adults. In addition, using principal component and regression analyses, we found that the first extracted EEG component, which represented mainly theta, alpha and beta powers, correlated with spatial working memory performance in older adults, but not in young adults. These findings are consistent with the theory that the neurobiological bases of working memory performance may differ between young and older adults. However, individual measures of resting-state EEG activity could not be used as reliable biomarkers to predict individual allocentric spatial working memory performance in young or older adults.

Resting-State EEG Microstates Parallel Age-Related Differences in Allocentric Spatial Working Memory Performance.

Alterations of resting-state EEG microstates have been associated with various neurological disorders and behavioral states. Interestingly, age-related differences in EEG microstate organization have also been reported, and it has been suggested that resting-state EEG activity may predict cognitive capacities in healthy individuals across the lifespan. In this exploratory study, we performed a microstate analysis of resting-state brain activity and tested allocentric spatial working memory performance in healthy adult individuals: twenty 25-30-year-olds and twenty-five 64-75-year-olds. We found a lower spatial working memory performance in older adults, as well as age-related differences in the five EEG microstate maps A, B, C, C' and D, but especially in microstate maps C and C'. These two maps have been linked to neuronal activity in the frontal and parietal brain regions which are associated with working memory and attention, cognitive functions that have been shown to be sensitive to aging. Older adults exhibited lower global explained variance and occurrence of maps C and C'. Moreover, although there was a higher probability to transition from any map towards maps C, C' and D in young and older adults, this probability was lower in older adults. Finally, although age-related differences in resting-state EEG microstates paralleled differences in allocentric spatial working memory performance, we found no evidence that any individual or combination of resting-state EEG microstate parameter(s) could reliably predict individual spatial working memory performance. Whether the temporal dynamics of EEG microstates may be used to assess healthy cognitive aging from resting-state brain activity requires further investigation.

Attentional Measures of Memory in Typically Developing and Hypoxic-Ischemic Injured Infants.

Hypoxic-ischemic injury (HII) at birth has been found to relate to differences in development, including decreased memory performance. The current study assessed recognition memory in 6- and 12-month-old HII infants and typically developing (TD) infants using two eye-tracking paradigms well suited to explore explicit memory processes early in life: visual paired comparison (VPC) and relational memory (RM). During the VPC, infants were familiarized to a face and then tested for their novelty preference immediately and after a two-minute delay. At 6 months, neither HII nor TD showed a VPC novelty preference at immediate delay, but at 12 months, both groups did; after the two-minute delay, no group showed a novelty preference. During RM, infants were presented with blocks containing a learning phase with three different scene-face pairs, and a test phase with one of the three scenes and all three faces appearing simultaneously. When there was no interference from other scene-face pairs between learning and test, 6-month-old TD showed evidence of an early novelty preference, but when there was interference, they revealed an early familiarity preference. For 12-month-old TD, some evidence for a novelty preference during RM was seen regardless of interference. Although HII and TD showed similar recognition memory on the VPC, when looking at RM, HII infants showed subtle differences in their attention to the familiar and novel faces as compared to their TD peers, suggesting that there might be subtle differences in the underlying memory processing mechanisms between HII and TD. More work is needed to understand how these attentional patterns might be predictive of later memory outcomes.

Functional and Anatomic Consequences of Diabetic Pregnancy on Memory in Ten-Year-Old Children.

OBJECTIVE: Pregnancies complicated by diabetes mellitus impair offspring memory functions during infancy and early childhood. The purpose of this study was to investigate the long-term consequences of such pregnancies on memory and memory-related brain regions in 10-year-old children. METHODS: Nineteen children of diabetic mothers (CDMs) and 35 children of nondiabetic mothers participated in this 10-year follow-up study. Memory performance was assessed using a continuous recognition memory task during which children made old/new judgments in response to pictures of concrete and abstract objects presented after different lags or delays. In addition, the volume of the hippocampal formation (HF) was measured using high-resolution structural images. RESULTS: At 10 years of age, recognition memory performance of CDMs did not differ from children of nondiabetic mothers. Similarly, the volume of the HF did not differ between groups. However, the size of the HF in CDMs predicted the time those children needed to provide accurate responses in the continuous recognition memory task. CONCLUSIONS: CDMs do not show memory impairments by 10 years of age, despite evidence for such impairments early in life. However, subtle differences in underlying neural processes may still be present. These results have important implications for long-term cognitive development of CDMs.

Development of allocentric spatial memory abilities in children from 18 months to 5 years of age.

Episodic memories for autobiographical events that happen in unique spatiotemporal contexts are central to defining who we are. Yet, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. Here, we studied the development of allocentric spatial memory, a fundamental component of episodic memory, in two versions of a real-world memory task requiring 18 month- to 5-year-old children to search for rewards hidden beneath cups distributed in an open-field arena. Whereas children 25-42-months-old were not capable of discriminating three reward locations among 18 possible locations in absence of local cues marking these locations, children older than 43 months found the reward locations reliably. These results support previous findings suggesting that allocentric spatial memory, if present, is only rudimentary in children under 3.5 years of age. However, when tested with only one reward location among four possible locations, children 25-39-months-old found the reward reliably in absence of local cues, whereas 18-23-month-olds did not. Our findings thus show that the ability to form a basic allocentric representation of the environment is present by 2 years of age, and its emergence coincides temporally with the offset of infantile amnesia. However, the ability of children to distinguish and remember closely related spatial locations improves from 2 to 3.5 years of age, a developmental period marked by persistent deficits in long-term episodic memory known as childhood amnesia. These findings support the hypothesis that the differential maturation of distinct hippocampal circuits contributes to the emergence of specific memory processes during early childhood.

Postnatal development of the hippocampal formation: a stereological study in macaque monkeys.

We performed a stereological analysis of neuron number, neuronal soma size, and volume of individual regions and layers of the macaque monkey hippocampal formation during early postnatal development. We found a protracted period of neuron addition in the dentate gyrus throughout the first postnatal year and a concomitant late maturation of the granule cell population and individual dentate gyrus layers that extended beyond the first year of life. Although the development of CA3 generally paralleled that of the dentate gyrus, the distal portion of CA3, which receives direct entorhinal cortex projections, matured earlier than the proximal portion of CA3. CA1 matured earlier than the dentate gyrus and CA3. Interestingly, CA1 stratum lacunosum-moleculare, in which direct entorhinal cortex projections terminate, matured earlier than CA1 strata oriens, pyramidale, and radiatum, in which the CA3 projections terminate. The subiculum developed earlier than the dentate gyrus, CA3, and CA1, but not CA2. However, similarly to CA1, the molecular layer of the subiculum, in which the entorhinal cortex projections terminate, was overall more mature in the first postnatal year compared with the stratum pyramidale in which most of the CA1 projections terminate. Unlike other hippocampal fields, volumetric measurements suggested regressive events in the structural maturation of presubicular neurons and circuits. Finally, areal and neuron soma size measurements revealed an early maturation of the parasubiculum. We discuss the functional implications of the differential development of distinct hippocampal circuits for the emergence and maturation of different types of "hippocampus-dependent" memory processes, including spatial and episodic memories.

Quantitative analysis of postnatal neurogenesis and neuron number in the macaque monkey dentate gyrus.

The dentate gyrus is one of only two regions of the mammalian brain where substantial neurogenesis occurs postnatally. However, detailed quantitative information about the postnatal structural maturation of the primate dentate gyrus is meager. We performed design-based, stereological studies of neuron number and size, and volume of the dentate gyrus layers in rhesus macaque monkeys (Macaca mulatta) of different postnatal ages. We found that about 40% of the total number of granule cells observed in mature 5-10-year-old macaque monkeys are added to the granule cell layer postnatally; 25% of these neurons are added within the first three postnatal months. Accordingly, cell proliferation and neurogenesis within the dentate gyrus peak within the first 3 months after birth and remain at an intermediate level between 3 months and at least 1 year of age. Although granule cell bodies undergo their largest increase in size during the first year of life, cell size and the volume of the three layers of the dentate gyrus (i.e. the molecular, granule cell and polymorphic layers) continue to increase beyond 1 year of age. Moreover, the different layers of the dentate gyrus exhibit distinct volumetric changes during postnatal development. Finally, we observe significant levels of cell proliferation, neurogenesis and cell death in the context of an overall stable number of granule cells in mature 5-10-year-old monkeys. These data identify an extended developmental period during which neurogenesis might be modulated to significantly impact the structure and function of the dentate gyrus in adulthood.