Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255‐257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A‐>B, B‐>C, C‐>D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A‐>C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre‐experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre‐experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to‐be‐learned relations were arbitrary. However, accuracy improved for older adults when they could use pre‐experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to ventromedial prefrontal and anterior temporal regions may have resulted in an inability to use prior knowledge to flexibly express indirect relational knowledge. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Older adults typically exhibit poorer face recognition compared to younger adults. These recognition differences may be due to underlying age-related changes in eye movement scanning. We examined whether older adults’ recognition could be improved by yoking their eye movements to those of younger adults. Participants studied younger and older faces, under free viewing conditions (bases), through a gaze-contingent moving window (own), or a moving window which replayed the eye movements of a base participant (yoked). During the recognition test, participants freely viewed the faces with no viewing restrictions. Own-age recognition biases were observed for older adults in all viewing conditions, suggesting that this effect occurs independently of scanning. Participants in the bases condition had the highest recognition accuracy, and participants in the yoked condition were more accurate than participants in the own condition. Among yoked participants, recognition did not depend on age of the base participant. These results suggest that successful encoding for all participants requires the bottom-up contribution of peripheral information, regardless of the locus of control of the viewer. Although altering the pattern of eye movements did not increase recognition, the amount of sampling of the face during encoding predicted subsequent recognition accuracy for all participants. Increased sampling may confer some advantages for subsequent recognition, particularly for people who have declining memory abilities.

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The preterm cerebellum is vulnerable to impaired development impacting long-term outcome. Preterm newborns (<32 weeks) underwent serial magnetic resonance imaging (MRI) scans. The association between parental education and cerebellar volume at each time point was assessed, adjusting for age at scan. In 26 infants, cerebellar volumes at term (P = .001), but not birth (P = .4), were associated with 2-year volumes. For 1 cm(3) smaller cerebellar volume (4% total volume) at term, the cerebellum was 3.18 cm(3) smaller (3% total volume) by 2 years. Maternal postsecondary education was not associated with cerebellar volume at term (P = .16). Maternal postsecondary education was a significant confounder in the relationship between term and 2-year cerebellar volumes (P = .016), with higher education associated with improved volumes by 2 years. Although preterm birth has been found to be associated with smaller cerebellar volumes at term, maternal postsecondary education is associated with improved growth detectable by 2 years.

Background Human studies investigating the link between postnatal polyunsaturated fatty acids and preterm brain growth are limited, despite emerging evidence of potential effects on outcomes. Methods Sixty preterm neonates <32 weeks gestational age with MRI scanning at near-birth and near-term age were assessed for brain tissue volumes including cortical grey matter, white matter, deep grey matter, cerebellum, brainstem and ventricular cerebrospinal fluid. Red blood cell fatty acid content was evaluated within 1 week of each MRI scan. Neurodevelopmental outcome at 30-36 months corrected age was assessed. Results Adjusting for potential confounders, higher near-birth docosahexaenoic acid levels are associated with larger cortical grey matter, deep grey matter, and brainstem volumes, and higher near-term levels with larger deep grey matter, cerebellar, and brainstem volumes at near-term age; lower near-birth linoleic acid levels are correlated with larger white matter volume at near-term age. By 30-36 months corrected age, larger cortical and deep grey matter, cerebellar, and brainstem volumes by term age are associated with improved language scores, and larger cerebellar and brainstem volumes with improved motor scores. Conclusion Specific polyunsaturated fatty acid levels have differential and time-dependent associations with brain region growth. Larger brain volumes are associated with improved outcomes at preschool age.

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Highlights Cohort study of neonatal encephalopathy using continuous glucose monitoring. Higher glucose on day 1 associated with widespread changes in brain microstructure. Lower glucose not associated with brain microstructural changes. No changes in MR spectroscopy found related to higher or lower glucose.

Background and Objectives:Seizures are common during neonatal encephalopathy, but the contribution of seizure burden to outcomes remains controversial. This study aims to examine the relationship between electrographic seizure burden and neurological outcomes after neonatal encephalopathy.Methods:This prospective cohort study recruited newborns ≥36 weeks PMA around 6 hours of life between August 2014 to November 2019 from a Neonatal Intensive Care Unit. Participants underwent continuous electroencephalography for at least 48 hours, brain MRI within 3-5 days of life, and structured follow-up at 18 months. Electrographic seizures were identified by board-certified neurophysiologists, and quantified as total seizure burden and maximum hourly seizure burden. A medication exposure score was calculated based on all anti-seizure medications given during NICU admission. Brain MRI injury severity was classified based on basal ganglia and watershed scores. Developmental outcomes were measured using the Bayley Scales of Infant Development, 3rdEdition. Multivariable regression analyses were performed, adjusting for significant potential confounders.Results:Of 108 enrolled subjects, 98 subjects had cEEG and MRI data collected, of which 5 were lost to follow-up, and 6 died before age 18 months. All subjects with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21(24%) newborns, with a total seizure burden mean of 12.5 ± 36.4 minutes, and a maximum hourly seizure burden mean of 4 ± 10 min/hr. After adjusting for MRI brain injury severity and medication exposure, total seizure burden was significantly associated with lower cognitive (-0.21, 95%CI -0.33 – -0.08, p=0.002) and language (-0.25, 95%CI -0.39 – -0.11, p=0.001) scores at 18 months. Total seizure burden of 60 minutes was associated with 15-point decline in language scores, and 70 minutes for cognitive scores. However, seizure burden was not significantly associated with epilepsy, neuromotor score, or cerebral palsy (p>0.1).Discussion:Higher seizure burden during neonatal encephalopathy was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to anti-seizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during neonatal encephalopathy independently contribute to long-term outcomes.