This functional magnetic resonance imaging study investigated the relationship between the neural correlates of associative memory encoding, callosal integrity, and memory performance in older adults. Thirty-six older and 18 young subjects were scanned while making relational judgments on word pairs. Neural correlates of successful encoding (subsequent memory effects) were identified by contrasting the activity elicited by study pairs that were correctly identified as having been studied together with the activity elicited by pairs wrongly judged to have come from different study trials. Subsequent memory effects common to the 2 age groups were identified in several regions, including left inferior frontal gyrus and bilateral hippocampus. Negative effects (greater activity for forgotten than for remembered items) in default network regions in young subjects were reversed in the older group, and the amount of reversal correlated negatively with memory performance. Additionally, older subjects' subsequent memory effects in right frontal cortex correlated positively with anterior callosal integrity and negatively with memory performance. It is suggested that recruitment of right frontal cortex during verbal memory encoding may reflect the engagement of processes that compensate only partially for age-related neural degradation.

Dopamine is important to learning and plasticity. Dopaminergic drugs are the focus of many therapies targeting the motor system, where high inter-individual differences in response are common. The current study examined the hypothesis that genetic variation in the dopamine system is associated with significant differences in motor learning, brain plasticity, and the effects of the dopamine precursor L-Dopa. Skilled motor learning and motor cortex plasticity were assessed using a randomized, double-blind, placebo-controlled, crossover design in 50 healthy adults during two study weeks, one with placebo and one with L-Dopa. The influence of five polymorphisms with established effects on dopamine neurotransmission was summed using a gene score, with higher scores corresponding to higher dopaminergic neurotransmission. Secondary hypotheses examined each polymorphism individually. While training on placebo, higher gene scores were associated with greater motor learning (p = .03). The effect of L-Dopa on learning varied with the gene score (gene score*drug interaction, p = .008): participants with lower gene scores, and thus lower endogenous dopaminergic neurotransmission, showed the largest learning improvement with L-Dopa relative to placebo (p<.0001), while L-Dopa had a detrimental effect in participants with higher gene scores (p = .01). Motor cortex plasticity, assessed via transcranial magnetic stimulation (TMS), also showed a gene score*drug interaction (p = .02). Individually, DRD2/ANKK1 genotype was significantly associated with motor learning (p = .02) and its modulation by L-Dopa (p<.0001), but not with any TMS measures. However, none of the individual polymorphisms explained the full constellation of findings associated with the gene score. These results suggest that genetic variation in the dopamine system influences learning and its modulation by L-Dopa. A polygene score explains differences in L-Dopa effects on learning and plasticity most robustly, thus identifying distinct biological phenotypes with respect to L-Dopa effects on learning and plasticity. These findings may have clinical applications in post-stroke rehabilitation or the treatment of Parkinson's disease.

Event related potentials (ERPs) were recorded from samples of young (18–29yrs) and older (63–77yrs) subjects 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 than in young subjects. 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 `mid-frontal old/new effect' – could be identified in the young subjects only. This age-related difference in the sensitivity of ERPs to familiarity was also evident in sub-groups of young and older subjects in whom familiarity-based recognition performance was equivalent. Thus, the inability to detect a reliable mid-frontal old/new effect in older subjects 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.

The neural correlates of episodic retrieval ('recollection') have been shown to differ according to the content of retrieved episodes. It has been hypothesized that these content-dependent differences reflect the 'reinstatement' of encoding-related processes or representations at the time of recollection. It remains unclear, however, whether these effects directly reflect the recollection of differential episodic content, as would be predicted by the reinstatement hypothesis, or whether they are instead associated with processes that are contingent on successful recollection. To address this issue, the present study employed event-related potentials (ERPs), permitting the investigation of the temporal dynamics of content-dependent neural effects during retrieval, and in particular, their onset with respect to well-established ERP correlates of recollection, such as the left parietal old-new effect. Subjects studied a series of words that were each presented in the context of one of two encoding tasks. One task required the covert generation of a sentence incorporating each word, whereas the other required imagining the object corresponding to each word within a superimposed scenic picture. Memory for the words was subsequently tested with the 'remember/know' procedure. ERPs elicited by recollected words differed according to the prior encoding history of the word, beginning at approximately 300 ms following word onset. These content-dependent ERP differences were maximal over the anterior scalp and, importantly, onset as early as the left parietal old-new effect. The findings demonstrate that content-dependent neural activity during retrieval can occur in a timeframe that is compatible with a direct role in the recollection and representation of episodic information.

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