Knut Overbye

Grid cells in the human entorhinal cortex (EC) play a critical role in spatial navigation and memory. The EC is also one of the first regions affected by ageing and Alzheimer’s disease. This pre-registered functional magnetic resonance imaging (fMRI) study aimed to detect grid-cell-like signals (GLS) in a passive virtual navigation task. Contrary to our hypotheses and previous findings, we did not observe significant GLS at a population level, even in younger participants. Further exploratory analyses investigated the impact of task-engagement, as inferred from object-location memory performance, and showed no relationship with GLS magnitude. We also examined potential influences of a confounding one-fold directional signal and various data-processing choices but observed no consistent patterns. Our findings, consistent with recent null results from similar studies, suggest that passive navigation paradigms may be insufficient for reliably eliciting grid-like signals in human fMRI.

The hippocampus and cortices of the medial temporal lobe (MTL) are increasingly implicated in working memory, particularly for tasks requiring complex, high-resolution relational binding, but their precise contributions—particularly during delay maintenance—remain debated. Using functional magnetic resonance imaging (fMRI), we investigated the involvement of hippocampal and cortical MTL in a demanding allocentric working memory task requiring high-resolution, relational binding. During fMRI, 128 healthy human adults (92 females) aged 20–83 (mean 39) years performed a task in which object–location bindings had to be learned, maintained, and manipulated across an 8 second delay. The design included a passive viewing condition to control for perceptual and attentional demands and a staircase procedure to balance task difficulty across participants. Across the full sample, anterior and mid hippocampal subregions and cortical MTL areas were engaged during encoding. In the delay phase, we observed a non-uniform pattern, with hippocampal and entorhinal deactivation alongside perirhinal and parahippocampal activation. During test, activation occurred in posterior hippocampus and several cortical MTL regions. Contrary to predictions, hippocampal and cortical MTL activation did not vary with performance among younger adults. Instead, differences emerged in a left temporoparietal cluster, potentially reflecting verbal encoding strategies. Older adults, relative to younger adults with the most comparable performance levels, showed lower anterior hippocampal activation and smaller correct–passive viewing differences in perirhinal and parahippocampal cortices. Taken together, these findings demonstrate distinct phase-specific hippocampal and cortical MTL involvement across the temporal unfolding of allocentric working memory, with evidence of hippocampal engagement even during the delay, yet the absence of MTL-performance associations among younger adults suggests this involvement, while robust, may play a more auxiliary role.

How environmental variation shapes the human cerebral cortex remains incompletely understood. We compared cortical brainprints based in 210 twins (71 MZ and 34 DZ pairs, age 16-78 years) to distinguish prenatal, adult naturalistic and experimentally induced environmental variation from genetic contributions. Genetic effects were reflected in higher brainprint similarity within monozygotic (MZ) than dizygotic (DZ) pairs. Early environmental contributions were evident in lower brainprint similarity in MZ twin pairs with larger birthweight discordances, driven by area across the cortical ribbon. Later within-pair environmental differences in adult weight and lifestyle had minimal influence. Still, a 10-week virtual-reality navigation intervention revealed training-induced changes in the gray-white interface, with curvature and area changes supported by microstructural reconfigurations. In support of gene-environment interactions, relative brainprint similarity increased in MZ but diverged in DZ pairs following training. The results demonstrate that in adulthood, early life environmental difference persistently contributes to make the cortical architecture of genetically identical twins deviate. Environmental influence in adulthood in the form of training can still affect similarity of twin brainprints at the grey-white-matter boundary. These findings show that distinct environmental influences at prenatal and adult stage are differentially expressed across cortical features within a genetically informed framework.

Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and life-long positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4-82 years of age, w/ 386 monozygotic twins, followed for up to 8.3 years w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.

Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and life-long positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4-82 years of age, w/ 386 monozygotic twins, followed for up to 8.3 years w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.

Human cognitive development is manifold, with different functions developing at different speeds at different ages. Attention is an important domain of this cognitive development, and involves distinct developmental trajectories in separate functions, including conflict processing, selection of sensory input and alertness. In children, several studies using the Attention Network Test (ANT) have investigated the development of three attentional networks that carry out the functions of executive control, orienting and alerting. There is, however, a lack of studies on the development of these attentional components across adolescence, limiting our understanding of their protracted development. To fill this knowledge gap, we performed a mixed cross-sectional and longitudinal study using mixed methods to examine the development of the attentional components and their intraindividual variability from late childhood to young adulthood (n = 287, n observations = 408, age range = 8.5–26.7 years, mean follow up interval = 4.4 years). The results indicated that executive control stabilized during late adolescence, while orienting and alerting continued to develop into young adulthood. In addition, a continuous development into young adulthood was observed for the intraindividual variability measures of orienting and alerting. In a subsample with available magnetic resonance imaging (MRI) data (n =169, n observations = 281), higher alerting scores were associated with thicker cortices within a right prefrontal cortical region and greater age-related cortical thinning in left rolandic operculum, while higher orienting scores were associated with greater age-related cortical thinning in frontal and parietal regions. Finally, increased consistency of orienting performance was associated with thinner cortex in prefrontal regions and reduced age-related thinning in frontal regions.

Cognitive control enables goal-oriented adaptation to a fast-changing environment and has a slow developmental trajectory that spans into young adulthood. The specifics of this development are still poorly understood, as are the neurodevelopmental mechanisms that drive it. In a cross-sectional sample of participants 8-19 years old (n = 108), we used blind source separation of EEG data recorded in a Flanker task to derive electrophysiological measures of attention and the processing of cognitive conflict, including a frontal negative component corresponding to the N2 and a parietal positive component corresponding to the P3. Additionally, we examined multiple behavioral measures of interference control derived from the Flanker, Stroop, and Anti-saccade tasks. We found a positive association between age and the amplitude of the parietal positive component, while there was no relationship between age and the amplitude of the frontal negative component. A stronger frontal negative amplitude was, however, age-independently related to better performance on both Stroop and Anti-saccade measures of interference control. Finally, we examined post-conflict behavioral adjustment on the Flanker task. A Gratton effect was found with slower reaction times on current congruent and better accuracy on current incongruent trials when preceded by incongruent as opposed to congruent trials. The Gratton effect on accuracy was positively associated with age. Together, the findings suggest a multifaceted developmental pattern in neurocognitive mechanisms for conflict processing across adolescence, with a more protracted development of the parietal positive compared to the frontal negative component.