Abstract The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in ...Alzheimer’s disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.
Small vessel disease (SVD) is a disorder that causes vascular lesions in the entire parenchyma of the human brain. At present, it is not well understood how primary and secondary damage interact to ...give rise to the complex scenario of white matter (WM) and grey matter (GM) lesions. Using novel cross-sectional and longitudinal connectomic approaches, we unveil the bidirectional nature of GM and WM changes, that is, primary cortical neurodegeneration that leads to secondary alterations in vascular border zones, and WM lesions that lead to secondary neurodegeneration in cortical projecting areas. We found this GM-WM interaction to be essential for executive cognitive performance. Moreover, we also observed that the interlocked degeneration of GM and WM over time associates with prototypical expression levels of genes potentially linked to SVD. Among these connectomic-genetic intersections, we found that the Androgen Receptor (AR) gene, is a particularly central candidate gene that might confer key vulnerability for brain lesion development in SVD. In conclusion, this study advances in the understanding of the bidirectional relationships between GM and WM lesions, primary and secondary vascular neurodegeneration, and sheds light on the genetic signatures of SVD.
•We described the bidirectional nature of neurodegeneration (ND) and vascular damage (VD) in the small vessel disease (SVD).•ND-VD bidirectional connectomics are key to understand the associated cognitive changes.•ND-VD connectomics relates to cortical expression levels of candidate genes linked to SVD.•Androgen Receptor gene confers central vulnerability for brain lesion development in SVD.•This study describes the intersection of primary and secondary ND and VD, and their potential genetic signatures in SVD.
The ability to produce novel ideas is central to societal progress and innovation; however, little is known about the biological basis of creativity. Here, we investigate the organization of brain ...networks that support creativity by combining functional neuroimaging data with gene expression information. Given the multifaceted nature of creative thinking, we hypothesized that distributed connectivity would not only be related to individual differences in creative ability, but also delineate the cortical distributions of genes involved in synaptic plasticity. We defined neuroimaging phenotypes using a graph theory approach that detects local and distributed network circuits, then characterized the spatial associations between functional connectivity and cortical gene expression distributions. Our findings reveal strong spatial correlations between connectivity maps and sets of genes devoted to synaptic assembly and signaling. This connectomic-transcriptome approach thus identifies gene expression profiles associated with high creative ability, linking cognitive flexibility to neural plasticity in the human brain.
The relationship between human brain connectomics and genetic evolutionary traits remains elusive due to the inherent challenges in combining complex associations within cerebral tissue. In this ...study, insights are provided about the relationship between connectomics, gene expression and divergent evolutionary pathways from non-human primates to humans. Using in vivo human brain resting-state data, we detected two co-existing idiosyncratic functional systems: the segregation network, in charge of module specialization, and the integration network, responsible for information flow. Their topology was approximated to whole-brain genetic expression (Allen Human Brain Atlas) and the co-localization patterns yielded that neuron communication functionalities-linked to Neuron Projection-were overrepresented cell traits. Homologue-orthologue comparisons using dN/dS-ratios bridged the gap between neurogenetic outcomes and biological data, summarizing the known evolutionary divergent pathways within the Homo Sapiens lineage. Evidence suggests that a crosstalk between functional specialization and information flow reflects putative biological qualities of brain architecture, such as neurite cellular functions like axonal or dendrite processes, hypothesized to have been selectively conserved in the species through positive selection. These findings expand our understanding of human brain function and unveil aspects of our cognitive trajectory in relation to our simian ancestors previously left unexplored.
Abstract Objectives How does creative expression change across the lifespan? While creativity is generally preserved well into adulthood, certain cognitive functions, such as episodic detail and ...ideational fluency, have been shown to decline with age. The present study employs computational linguistic analyses to investigate the salient features of creative writing in older adults. Methods We collected short stories from a sample of 50 older adults (age 65≤) which were subsequently rated for creativity by an independent set of participants. Mixed-effects linear regression models were used to describe semantic diversity and perceptual details as predictors of creativity. Semantic diversity reflects the extent to which a narrative connects divergent ideas and is closely associated with creativity. Perceptual details, characterized by sensorial descriptions, have been previously associated with creative writing and may serve to transport readers to alternative times and places. Additionally, we compare these measures to a previously collected sample of stories from younger adults. Results Results indicate that the presence of perceptual details and semantic diversity were significant positive predictors of creativity (p<.05). Moreover, we find that stories written by older adults contain fewer perceptual details compared with stories written by younger adults. Discussion These results advance our understanding of age-related changes in creativity and highlight the potential role of episodic simulation in the writing of creative short stories.
Recent studies of creative cognition have revealed interactions between functional brain networks involved in the generation of novel ideas; however, the neural basis of creativity is highly complex ...and presents a great challenge in the field of cognitive neuroscience, partly because of ambiguity around how to assess creativity. We applied a novel computational method of verbal creativity assessment—semantic distance—and performed weighted degree functional connectivity analyses to explore how individual differences in assembly of resting-state networks are associated with this objective creativity assessment. To measure creative performance, a sample of healthy adults (
= 175) completed a battery of divergent thinking (DT) tasks, in which they were asked to think of unusual uses for everyday objects. Computational semantic models were applied to calculate the semantic distance between objects and responses to obtain an
objective measure of DT performance. All participants underwent resting-state imaging, from which we computed voxel-wise connectivity matrices between all gray matter voxels. A linear regression analysis was applied between DT and weighted degree of the connectivity matrices. Our analysis revealed a significant connectivity decrease in the visual-temporal and parietal regions, in relation to increased levels of DT. Link-level analyses showed higher local connectivity within visual regions was associated with lower DT, whereas projections from the precuneus to the right inferior occipital and temporal cortex were positively associated with DT. Our results demonstrate differential patterns of resting-state connectivity associated with individual creative thinking ability, extending past work using a new application to automatically assess creativity via semantic distance.
Creative ideas are thought to result from flexible recombination of concepts from memory. A growing number of behavioural and neuroscientific studies provide evidence of a link between episodic ...memory and divergent thinking; however, little is known about the potential contributions of autobiographical memory to creative ideation. To provide a novel perspective on this issue, we assessed measures of divergent and convergent creative thinking in a cohort (n =
14
) of rare individuals showing Highly Superior Autobiographical Memory (HSAM). The HSAM cohort completed memory tasks in addition to a battery of creativity measures, including the Alternative Uses Task, Consequences Task and Remote Associates Task. We performed statistical analyses to establish whether there were any significant differences between HSAM and controls (n =
28
) across these measures. Although HSAM participants were superior in the recall of autobiographical events compared to controls, we observed no overall difference between the groups in relation to the creativity measures. These findings suggest that the constructive episodic processes relevant to creative thinking are not enhanced in individuals with HSAM, perhaps because they are compulsively and narrowly focused on consolidation and retrieval of autobiographical events.
Amyloid‐beta (Aβ) plaques and tau neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD); their contribution to neurodegeneration and clinical manifestations are critical in ...understanding preclinical AD. At present, the mechanisms related to Aβ and tau pathogenesis leading to cognitive decline in older adults remain largely unknown. Here, we examined graph theory‐based positron emission tomography (PET) analytical approaches, within and between tau and Aβ PET modalities, and tested the effects on cognitive changes in cognitively normal older adults (CN). Particularly, we focused on the network interdigitations of Aβ and tau deposits, along with cognitive test scores in CN at both baseline and 2‐year follow‐up (FU). We found highly significant Aβ‐tau network integrations in AD vulnerable areas, as well as significant associations between those Aβ‐tau interdigitations and general cognitive impairment in CN at baseline and FU. Our findings suggest a distinctive contribution of interlinking network relationships between Aβ and tau deposits in heteromodal areas of the human brain. They support a network‐based interaction between Aβ and tau accumulations as a key factor for cognitive deterioration in CN prior to dementia.
We examined network interaction patterns within single positron emission tomography (PET) modality, such as Aß‐to‐Aß or Tau‐to‐Tau correlations, and between different PET modalities, such as Aß‐to‐Tau or Tau‐to‐Aß, at high‐resolution (voxel‐level) in cognitively normal older adults (CN), using a graph theory‐based analysis. We observed that the PET uptakes derived from Aß‐to‐Tau interdigitations were significantly associated with Alzheimer's Disease Assessment Scale‐Cognitive Subscale in AD vulnerable brain areas, a finding confirmed by our longitudinal investigation. Therefore, our work suggests the preceding contribution of network interactions between Aß and tau deposits to explain initial cognitive changes in CN prior to the conversion of dementia.
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