Marianne de Chastelaine

On the elusive nature of sex differences in cognition: hormonal influences contributing to within-sex variation.

We argue that within-sex variation resulting from the prenatal organizational and adult activational effects of gonadal steroid hormones has the potential to obscure between sex differences in cognitive performance and functional cerebral asymmetry. Two putative markers for prenatal testosterone, finger ridge count (FRC) asymmetry and the 2D:4D finger length ratio, have been linked to within-sex variation in cognitive performance. In particular, FRC allows the identification of men and women who show a reversal of the typical sex-related pattern of task performance. Three paradigms for the study of activational effects—seasonal, menstrual, and diurnal hormonal cycles—have evaluated changes in task performance and functional cerebral asymmetry. The performance of sex-dimorphic, but not sex-neutral, tasks changes with estrogen across the menstrual cycle and with testosterone across its seasonal and diurnal cycles. Functional cerebral asymmetry also changes systematically across both the menstrual cycle and the diurnal testosterone cycle in such a way that suggests left hemisphere performance increases as testosterone levels decline whereas right hemisphere performance increases as estrogen levels decline. In studies of sex differences, such correlates of within-sex hormone-related differences are rarely measured or controlled. Whatever the explanation for the associations of putative markers and hormone cycles with differences in cognitive abilities and cerebral asymmetry, it is clear that these relationships have the potential to contribute to the elusive nature of sex differences in cognition and functional brain organization.

Changes in familiarity and recollection across the lifespan: an ERP perspective.

The ability to recognize previous experience depends on two neurocognitive processes, familiarity, fast-acting and relatively automatic, and recollection, slower-acting and more effortful. Familiarity appears to mature relatively early in development and is maintained with aging, whereas recollection shows protracted development and deteriorates with aging. To assess this model, ERP and behavioral data were recorded in children (9-10 years), adolescents (13-14), young (20-30) and older (65-85) adults during a recognition memory task in which the same items were studied and tested over four cycles. Participants decided whether each item was old or new and then whether the decision was associated with (Remember, R) or without (Know, K) contextual detail. Memory sensitivity was greatest in young adults, although all groups showed increases in memory sensitivity and R judgments with repetition. Familiarity-based processes (mid-frontal episodic memory, EM, effect) appeared to be used by adolescents, young and older adults, but apparently not to the same extent by children. Recollection-based processes (parietal EM effect) were recruited by children, adolescents and young adults, but to a much lesser extent by older adults. Repetition enhanced the parietal effect in all but older adults. However, post-hoc analyses indicated that reduced recollective processing was confined to poor-performing older adults. By contrast, children appeared to rely mainly on recollection concordant with their conservative decision criteria across tests. We conclude that episodic-memory development reflects the increasingly flexible and interchangeable use of familiarity and recollection with a breakdown in the latter at older ages, perhaps limited to poor-performing older adults.

Recollection-Related Increases in Functional Connectivity Predict Individual Differences in Memory Accuracy

Recollection involves retrieving specific contextual details about a prior event. Functional neuroimaging studies have identified several brain regions that are consistently more active during successful versus failed recollection—the “core recollection network.” In the present study, we investigated whether these regions demonstrate recollection-related increases not only in activity but also in functional connectivity in healthy human adults. We used fMRI to compare time-series correlations during successful versus unsuccessful recollection in three separate experiments, each using a different operational definition of recollection. Across experiments, a broadly distributed set of regions consistently exhibited recollection-related increases in connectivity with different members of the core recollection network. Regions that demonstrated this effect included both recollection-sensitive regions and areas where activity did not vary as a function of recollection success. In addition, in all three experiments the magnitude of connectivity increases correlated across individuals with recollection accuracy in areas diffusely distributed throughout the brain. These findings suggest that enhanced functional interactions between distributed brain regions are a signature of successful recollection. In addition, these findings demonstrate that examining dynamic modulations in functional connectivity during episodic retrieval will likely provide valuable insight into neural mechanisms underlying individual differences in memory performance.

Effects of age on the neural correlates of familiarity as indexed by erps

ERPs were recorded from samples of young (18–29 years) and older (63–77 years) participants while they performed a modified “remember–know” recognition memory test. ERP correlates of familiarity-driven recognition were obtained by contrasting the waveforms elicited by unrecollected test items accorded “confident old” and “confident new” judgments. Correlates of recollection were identified by contrasting the ERPs elicited by items accorded “remember” and confident old judgments. Behavioral analyses revealed lower estimates of both recollection and familiarity in older participants than in young participants. The putative ERP correlate of recollection—the “left parietal old–new effect”—was evident in both age groups, although it was slightly but significantly smaller in the older sample. By contrast, the putative ERP correlate of familiarity—the “midfrontal old–new effect”—could be identified in young participants only. This age-related difference in the sensitivity of ERPs to familiarity was also evident in subgroups of young and older participants, in whom familiarity-based recognition performance was equivalent. Thus, the inability to detect a reliable midfrontal old–new effect in older participants was not a consequence of an age-related decline in the strength of familiarity. These findings raise the possibility that familiarity-based recognition memory depends upon qualitatively different memory signals in older and young adults.

Effects of multiple study-test repetition on the neural correlates of recognition memory: ERPs dissociate remembering and knowing.

Event-related potential (ERP) frontal (300-500 ms) and parietal (500-700 ms) episodic memory (EM) effects are thought to reflect, respectively, familiarity and recollection. However, as most ERP studies use preexperimentally familiar items, an alternative idea is that the frontal EM effect reflects conceptual priming. Repetition of unnameable symbols was used to assess modulations of the putative ERP indices of familiarity and recollection. The same symbols were viewed in each of 4 study/test blocks. Increases in familiarity and conceptual processing of symbols did not modulate the frontal EM effect, suggesting that it reflects neither familiarity nor conceptual priming. The magnitude of the parietal EM effect increased and its onset latency decreased across tests for items given remember (R) but not know (K) judgments. R and K old-new topographies differed. These findings support dual-process proposals that familiarity- and recollection-based processes are distinct.

Comparison of the neural correlates of encoding item-item and item-context associations

fMRI was employed to investigate the role of the left inferior frontal gyrus (LIFG) in the encoding of item-item and item-context associations. On each of a series of study trials subjects viewed a picture that was presented either to the left or right of fixation, along with a subsequently presented word that appeared at fixation. Memory was tested in a subsequent memory test that took place outside of the scanner. On each test trial one of two forced choice judgments was required. For the associative test, subjects chose between the word paired with the picture at study and a word studied on a different trial. For the source test, the judgment was whether the picture had been presented on the left or right. Successful encoding of associative information was accompanied by subsequent memory effects in several cortical regions, including much of the LIFG. By contrast, successful source encoding was selectively associated with a subsequent memory effect in right fusiform cortex. The finding that the LIFG was enhanced during successful associative, but not source, encoding is interpreted in light of the proposal that subsequent memory effects are localized to cortical regions engaged by the on-line demands of the study task.

The Effects of Age on the Neural Correlates of Recollection Success, Recollection-Related Cortical Reinstatement, and Post-Retrieval Monitoring

Functional magnetic resonance imaging (fMRI) was used to investigate whether age-related differences in episodic memory performance are accompanied by a reduction in the specificity of recollected information. We addressed this question by comparing recollection-related cortical reinstatement in young and older adults. At study, subjects viewed objects and concrete words, making 1 of 2 different semantic judgments depending on the study material. Test items were words that corresponded to studied words or the names of studied objects. Subjects indicated whether each test item was recollected, familiar, or novel. Reinstatement of information differentiating the encoding tasks was quantified both with a univariate analysis of the fMRI signal and with a multivoxel pattern analysis, using a classifier that had been trained to discriminate between the 2 classes of study episode. The results of these analyses converged to suggest that reinstatement did not differ according to age. Thus, there was no evidence that specificity of recollected information was reduced in older individuals. Additionally, there were no age effects in the magnitude of recollection-related modulations in regional activity or in the neural correlates of post-retrieval monitoring. Taken together, the findings suggest that the neural mechanisms engaged during successful episodic retrieval can remain stable with advancing age.

Sensitivity of negative subsequent memory and task-negative effects to age and associative memory performance

The present fMRI experiment employed associative recognition to investigate the relationships between age and encoding-related negative subsequent memory effects and task-negative effects. Young, middle-aged and older adults (total n=136) were scanned while they made relational judgments on visually presented word pairs. In a later memory test, the participants made associative recognition judgments on studied, rearranged (items studied on different trials) and new pairs. Several regions, mostly localized to the default mode network, demonstrated negative subsequent memory effects in an across age-group analysis. All but one of these regions also demonstrated task-negative effects, although there was no correlation between the size of the respective effects. Whereas negative subsequent memory effects demonstrated a graded attenuation with age, task-negative effects declined markedly between the young and the middle-aged group, but showed no further reduction in the older group. Negative subsequent memory effects did not correlate with memory performance within any age group. By contrast, in the older group only, task-negative effects predicted later memory performance. The findings demonstrate that negative subsequent memory and task-negative effects depend on dissociable neural mechanisms and likely reflect distinct cognitive processes. The relationship between task-negative effects and memory performance in the older group might reflect the sensitivity of these effects to variations in amount of age-related neuropathology. This article is part of a Special Issue entitled SI: Memory.

The relationship between task-related and subsequent memory effects.

The primary aim of this fMRI study was to assess the proposal that negative subsequent memory effects—greater activity for later forgotten relative to later remembered study items—are localized to regions demonstrating task‐negative effects, and hence to potential components of the default mode network. Additionally, we assessed whether positive subsequent memory effects overlapped with regions demonstrating task‐positive effects. Eighteen participants were scanned while they made easy or difficult relational judgments on visually presented word pairs. Easy and hard task blocks were interleaved with fixation‐only rest periods. In the later unscanned test phase, associative recognition judgments were required on intact word pairs (studied pairs), rearranged pairs (pairs formed from words presented on different study trials) and new pairs. Subsequent memory effects were identified by contrasting the activity elicited by study pairs that went on to be correctly endorsed as intact versus incorrectly endorsed as rearranged. Task effects were identified by contrasting all study items and rest blocks. Both task‐negative and task‐positive effects were evident in widespread cortical regions and negative and positive subsequent memory effects were generally confined to task‐negative and task‐positive regions respectively. However, subsequent memory effects could be identified in only a fraction of task‐sensitive voxels and, unlike task effects, were insensitive to the difficulty manipulation. The findings for the negative subsequent memory effects are consistent with recent proposals that the default mode network is functionally heterogeneous, and suggest that these effects are not accurately characterized as reflections of the modulation of the network as a whole. Hum Brain Mapp 35:3687–3700, 2014.

Pre-stimulus neural activity predicts successful encoding of inter-item associations.

fMRI was employed to investigate the relationship between pre-stimulus neural activity and associative encoding of words and pictures in humans. While undergoing scanning, subjects studied randomly interleaved word or picture pairs. A pre-stimulus cue preceded the presentation of each study pair and signaled whether it would comprise words or pictures. Memory for the study pairs was later tested with an associative recognition test, which comprised word or picture pairs presented either in the same (intact) or a different (rearranged) pairing as at study, along with pairs of new items. The critical fMRI contrast was between study activity associated with pairs later correctly judged intact and pairs incorrectly judged as rearranged. A key question was whether material-selective pre-stimulus encoding effects could be identified which overlapped regions selectively activated by the respective study material. Picture-selective pre-stimulus effects were identified in bilateral fusiform and the intraparietal sulcus (IPS), whereas word-selective effects could not be identified. Material-invariant pre-stimulus subsequent memory effects were also identified in several neocortical regions as well as in the hippocampus. Whereas the loci of the neocortical effects suggest that they reflect the benefit to encoding that accrues from engagement of cognitive control processes, their magnitude was negatively correlated across subjects with associative recognition performance and positively related to false alarm rate. Conversely, the hippocampal effects also predicted unique variance in associative memory and were negatively related to hit rate. It is suggested that the neocortical pre-stimulus effects may reflect encoding processes that increase familiarity of single items, whereas the hippocampal pre-stimulus effects are proposed to reflect either the encoding of task-irrelevant features or the retrieval of task-relevant information associated with the pre-stimulus cues. Overall, the results provide evidence that pre-stimulus processes may be deleterious, rather than beneficial, to associative encoding.