Fast event-related mapping of fingertip population receptive fields in human somatosensory and motor cortex

The majority of fMRI studies investigating somatotopic body representations in the human cortex have used either block or phase-encoding stimulation designs. Event-related (ER) designs allow for more natural and flexible stimulation sequences, while enabling the independent estimation of responses to different body parts in the same cortical location. Here we compared an efficiency-optimized fast ER design (2s inter stimulus interval, ISI) to a slow ER design (8s ISI) for mapping fingertip voxelwise tuning properties in the sensorimotor cortex of 6 participants at 7 Tesla. The fast ER design resulted in similar, but more robust, estimates compared to the slow ER design. Concatenating the fast and slow ER data, we demonstrate in each individual brain the existence of two separate somatotopically-organized representations of the fingertips, one in S1 on the post-central gyrus and the other at the border of the motor and pre-motor cortices on the pre-central gyrus. In both post-central and pre-central representations, fingertip tuning width increases progressively, from narrowly-tuned Brodmann areas 3b and 4a respectively, towards parietal and frontal regions responding equally to all fingertips.

Neocortical pyramidal neurons with axons emerging from dendrites are frequent in non-primates, but rare in monkey and human

The canonical view of neuronal function is that inputs are received by dendrites and somata, become integrated in the somatodendritic compartment and upon reaching a sufficient threshold, generate axonal output with axons emerging from the cell body. The latter is not necessarily the case. Instead, axons may originate from dendrites. The terms “axon carrying dendrite” (AcD) and “AcD neurons” have been coined to describe this feature. Here, we report on the diversity of axon origins in neocortical pyramidal cells. We found that in non-primates (rodent, cat, ferret, pig), 10-21% of pyramidal cells of layers II-VI had an AcD. In marked contrast, in macaque and human, this proportion was lower, and it was particularly low for supragranular neurons. Unexpectedly, pyramidal cells in the white matter of postnatal cat and aged human cortex exhibit AcDs to much higher percentages. In rodent hippocampus, AcD cells are functionally ’privileged‘, since inputs here can circumvent somatic integration and lead to immediate action potential initiation in the axon. Our findings expand the current knowledge regarding the distribution and proportion of AcD cells in neocortial regions of non-primate taxa, which strikingly differs from primates where these cells are mainly found in deeper layers and white matter.

Cortical Cartography: Mapping Arealization Using Single-Cell Omics Technology

The cerebral cortex derives its cognitive power from a modular network of specialized areas processing a multitude of information. The assembly and organization of these regions is vital for human behavior and perception, as evidenced by the prevalence of area-specific phenotypes that manifest in neurodevelopmental and psychiatric disorders. Generations of scientists have examined the architecture of the human cortex, but efforts to capture the gene networks which drive arealization have been hampered by the lack of tractable models of human neurodevelopment. Advancements in “omics” technologies, imaging, and computational power have enabled exciting breakthroughs into the molecular and structural characteristics of cortical areas, including transcriptomic, epigenomic, metabolomic, and proteomic profiles of mammalian models. Here we review the single-omics atlases that have shaped our current understanding of cortical areas, and their potential to fuel a new era of multi-omic single-cell endeavors to interrogate both the developing and adult human cortex.

Plant Sterol-Poor Diet Is Associated with Pro-Inflammatory Lipid Mediators in the Murine Brain

Plant sterols (PSs) cannot be synthesized in mammals and are exclusively diet-derived. PSs cross the blood-brain barrier and may have anti-neuroinflammatory effects. Obesity is linked to lower intestinal uptake and blood levels of PSs, but its effects in terms of neuroinflammation—if any—remain unknown. We investigated the effect of high-fat diet-induced obesity on PSs in the brain and the effects of the PSs campesterol and β-sitosterol on in vitro microglia activation. Sterols (cholesterol, precursors, PSs) and polyunsaturated fatty acid-derived lipid mediators were measured in the food, blood, liver and brain of C57BL/6J mice. Under a PSs-poor high-fat diet, PSs levels decreased in the blood, liver and brain (>50%). This effect was reversible after 2 weeks upon changing back to a chow diet. Inflammatory thromboxane B2 and prostaglandin D2 were inversely correlated to campesterol and β-sitosterol levels in all brain regions. PSs content was determined post mortem in human cortex samples as well. In vitro, PSs accumulate in lipid rafts isolated from SIM-A9 microglia cell membranes. In summary, PSs levels in the blood, liver and brain were associated directly with PSs food content and inversely with BMI. PSs dampen pro-inflammatory lipid mediators in the brain. The identification of PSs in the human cortex in comparable concentration ranges implies the relevance of our findings for humans.

Oligodendrocytes are a lifelong source of nuclear and ribosomal material for neurons in the mouse brain

Nuclear and ribosomal components define cell identity and function by regulating chromatin dynamics, gene expression, and protein turnover. Here we report that in the mouse central nervous system (CNS) under normal conditions, neurons accumulate nuclear and ribosomal material of oligodendrocyte (OL) origin. We show that neuronal accumulation of OL-derived nuclear and ribosomal material is brain area-specific, and in the cortex and hippocampal dentate gyrus gradually propagates during postnatal brain maturation. We further demonstrate that OL-to-neuron material transfer persists throughout adulthood and responds to neuroinflammation. We found that satellite OL of the gray matter form internuclear contacts with receiving neurons in the mouse brain. Similar close internuclear associations between satellite OL and neurons are present in the adult human cortex. Our findings provide the first evidence of wide-spread dynamic and selective OL-to-neuron nuclear and ribosomal material transfer in the mouse CNS and indicate that satellite OL serve as powerful mediators of neuronal function. Equivalent processes may occur in the human CNS and cause neurological disorders when dysregulated.

Multi-task representations in human cortex transform along a sensory-to-motor hierarchy

Human cognition recruits diverse neural processes, yet the organizing computational and functional architectures remain unclear. Here, we characterized the geometry and topography of multi-task representations across human cortex using functional MRI during 26 cognitive tasks in the same subjects. We measured the representational similarity across tasks within a region, and the alignment of representations between regions. We found a cortical topography of representational alignment following a hierarchical sensory-association-motor gradient, revealing compression-then-expansion of multi-task dimensionality along this gradient. To investigate computational principles of multi-task representations, we trained multi-layer neural network models to transform empirical visual to motor representations. Compression-then-expansion organization in models emerged exclusively in a training regime where internal representations are highly optimized for sensory-to-motor transformation, and not under generic signal propagation. This regime produces hierarchically structured representations similar to empirical cortical patterns. Together, these results reveal computational principles that organize multi-task representations across human cortex to support flexible cognition.

Brief Postnatal Visual Deprivation Triggers Long-Lasting Interactive Structural and Functional Reorganization of the Human Cortex

Patients treated for bilateral congenital cataracts provide a unique model to test the role of early visual input in shaping the development of the human cortex. Previous studies showed that brief early visual deprivation triggers long-lasting changes in the human visual cortex. However, it remains unknown if such changes interact with the development of other parts of the cortex. With high-resolution structural and resting-state fMRI images, we found changes in cortical thickness within, but not limited to, the visual cortex in adult patients, who experienced transient visual deprivation early in life as a result of congenital cataracts. Importantly, the covariation of cortical thickness across regions was also altered in the patients. The areas with altered cortical thickness in patients also showed differences in functional connectivity between patients and normally sighted controls. Together, the current findings suggest an impact of early visual deprivation on the interactive development of the human cortex.