The human hippocampus is involved in forming new memories: damage impairs memory. The dual stream model suggests that object “what” representations from ventral stream temporal cortex project to the hippocampus via the perirhinal and then lateral entorhinal cortex, and spatial “where” representations from the dorsal parietal stream via the parahippocampal gyrus and then medial entorhinal cortex. The hippocampus can then associate these inputs to form episodic memories of what happened where. Diffusion tractography was used to reveal the direct connections of hippocampal system areas in humans. This provides evidence that the human hippocampus has extensive direct cortical connections, with connections that bypass the entorhinal cortex to connect with the perirhinal and parahippocampal cortex, with the temporal pole, with the posterior and retrosplenial cingulate cortex, and even with early sensory cortical areas. The connections are less hierarchical and segregated than in the dual stream model. This provides a foundation for a conceptualization for how the hippocampal memory system connects with the cerebral cortex and operates in humans. One implication is that prehippocampal cortical areas such as the parahippocampal TF and TH subregions and perirhinal cortices may implement specialized computations that can benefit from inputs from the dorsal and ventral streams.

The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better its roles in emotion and its disorders. The medial OFC and ventromedial prefrontal cortex have direct connections with the pregenual and subgenual parts of the anterior cingulate cortex; all of which are reward-related areas. The lateral OFC (OFClat) and its closely connected right inferior frontal gyrus (rIFG) have direct connections with the supracallosal anterior cingulate cortex; all of which are punishment or nonreward-related areas. The OFClat and rIFG also have direct connections with the right supramarginal gyrus and inferior parietal cortex, and with some premotor cortical areas, which may provide outputs for the OFClat and rIFG. Another key finding is that the ventromedial prefrontal cortex shares with the medial OFC especially strong outputs to the nucleus accumbens and olfactory tubercle, which comprise the ventral striatum, whereas the other regions have more widespread outputs to the striatum. Direct connections of the OFC and IFG were with especially the temporal pole part of the temporal lobe. The left IFG, which includes Broca’s area, has direct connections with the left angular and supramarginal gyri.

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Objective: Although previous studies postulated that physical and cognitive decline codeveloped in preclinical dementia, the interconnected relationship among subjective cognitive complaints (SCCs), objective cognitive performance, and physical activity remained hazy. We investigated the mediating roles of physical activity between subjective and objective cognition. Diffusion tensor imaging (DTI) was utilized to test our hypothesis that brain white matter microstructural changes underlie the physical-cognitive decline in subjective cognitive decline (SCD).Methods: We enrolled cognitively normal older adults aged > 50 years in the Community Medicine Research Center of Keelung Chang Gung Memorial Hospital during 2017–2020. Regression models analyzed mediation effects of physical activity between subjective and objective cognition. The self-reported AD8 questionnaire assessed SCCs. The SCD group, defined by AD8 score ≥ 2, further underwent diffusion MRI scans. Those who agreed to record actigraphy also wore the SOMNOwatch™ for 72 h. Spearman's correlation coefficients evaluated the associations of diffusion indices with physical activity and cognitive performance.Results: In 95 cognitively normal older adults, the AD8 score and the Montreal Cognitive Assessment (MoCA) score were mediated partially by the metabolic equivalent of the International Physical Activity Questionnaire-Short Form (IPAQ-SF MET) and fully by the sarcopenia score SARC-F. That is, the relation between SCCs and poorer cognitive performance was mediated by physical inactivity. The DTI analysis of 31 SCD participants found that the MoCA score correlated with mean diffusivity at bilateral inferior cerebellar peduncles and the pyramids segment of right corticospinal tract [p < 0.05, false discovery rate (FDR) corrected]. The IPAQ-SF MET was associated with fractional anisotropy (FA) at the right posterior corona radiata (PCR) (p < 0.05, FDR corrected). In 15 SCD participants who completed actigraphy recording, the patterns of physical activity in terms of intradaily variability and interdaily stability highly correlated with FA of bilateral PCR and left superior corona radiata (p < 0.05, FDR corrected).Conclusions: This study addressed the role of physical activity in preclinical dementia. Physical inactivity mediated the relation between higher SCCs and poorer cognitive performance. The degeneration of specific white matter tracts underlay the co-development process of physical-cognitive decline in SCD.

The cerebellum has long been known to play an important role in motor and balance control, and accumulating evidence has revealed that it is also involved in multiple cognitive functions. However, the evidence from neuroimaging studies and clinical observations is not well-integrated at the anatomical or molecular level. The goal of this review is to summarize and link different aspects of the cerebellum, including molecular patterning, functional topography images, and clinical cerebellar disorders. More specifically, we explored the potential relationships between the cerebrocerebellar connections and the expression of particular molecules and, in particular, zebrin stripe (a Purkinje cell-specific antibody molecular marker, which is a glycolytic enzyme expressed in cerebellar Purkinje cells). We hypothesized that the zebrin patterns contribute to cerebellar functional maps-especially when cerebrocerebellar circuit changes exist in cerebellar-related diseases. The zebrin stripe receives input from climbing fibers and project to different parts of the cerebral cortex through its cerebrocerebellar connection. Since zebrin-positive cerebellar Purkinje cells are resistant to excitotoxicity and cell injury while zebrin-negative zones are more prone to damage, we suggest that motor control dysfunction symptoms such as ataxia and dysmetria present earlier and are easier to observe than non-ataxia symptoms due to zebrin-negative cell damage by cerebrocerebellar connections. In summary, we emphasize that the molecular zebrin patterns provide the basis for a new viewpoint from which to investigate cerebellar functions and clinico-neuroanatomic correlations.