Brain Structure & Function最新文献

Understanding the neural processes underlying conscious perception remains a central goal in neuroscience. Visual illusions, whether static or dynamic, provide an effective ecological paradigm for studying conscious perception, as they induce subjective experiences from constant visual inputs. While previous neuroimaging studies have dissociated perceptual interpretation of visual motion from sensory input within the motion-sensitive area (hMT+) in humans, less is known about the role of the primary visual area (V1) and its relationship to hMT+ during a bistable perception. To address this, we conducted a layer-fMRI study at 7 T with human participants exposed to a bistable motion quartet stimulus. Despite a constant sensory input, the bistable motion quartet elicits switching horizontal and vertical apparent motion percepts likely due to lateral and feedback connections across low and high-level brain regions (feedback processing). As control, we used an "unambiguous" version of the motion quartet, hereafter referred to as "physical" motion stimulus, where horizontal and vertical motion is physically presented as visual stimulus in an alternated fashion (feedforward processing). With the advantage of a sub-millimeter resolution gained at ultra-high magnetic field (7 Tesla), we aimed to unveil the differential laminar modulation of V1 (early visual area) and hMT+ (high-order visual area) during the physical and bistable condition. Our results indicate that: (1) hMT+ functional activity correlates with conscious perception during both physical and ambiguous stimuli with similar strength. There is no evidence of differential laminar profiles in hMT+ between the two experimental conditions. (2) Between inducer squares, V1 shows a significantly reduced functional response to the ambiguous stimulus compared to the physical stimulus, as it primarily reflects feedback signals with diminished feedforward input. Distinct V1 laminar profiles differentiate the two experimental conditions. (3) The temporal dynamics of V1 and hMT+ become more similar during the ambiguous condition. (4) V1 exhibits reduced specificity to horizontal and vertical motion perception during the ambiguous condition at the retinotopic locations corresponding to the perceived motion. Our findings demonstrate that during the ambiguous condition, there is a stronger temporal coupling between hMT+ and V1 due to feedback signals from hMT+ to V1. Such feedback to V1 might be contributing to the stabilization of the vivid perception of directed motion at the face of constant ambiguous stimulation.

Alzheimer's disease currently has no cure and is usually detected too late for interventions to be effective. In this study we have focused on cognitively normal subjects to study the impact of risk factors on their long-range brain connections. To detect vulnerable connections, we devised a multiscale, hierarchical method for spatial clustering of the whole brain tractogram and examined the impact of age and APOE allelic variation on cognitive abilities and bundle properties including texture e.g., mean fractional anisotropy, variability, and geometric properties including streamline length, volume, shape, as well as asymmetry. We found that the third level subdivision in the bundle hierarchy provided the most sensitive ability to detect age and genotype differences associated with risk factors. Our results indicate that frontal bundles were a major age predictor, while the occipital cortex and cerebellar connections were important risk predictors that were heavily genotype dependent, and showed accelerated decline in fractional anisotropy, shape similarity, and increased asymmetry. Cognitive metrics related to olfactory memory were mapped to bundles, providing possible early markers of neurodegeneration. In addition, physiological metrics associated with cardiovascular disease risk were associated with changes in white matter tracts. Our novel method for a data driven analysis of sensitive changes in tractography may differentiate populations at risk for AD and isolate specific vulnerable networks.

The hypothalamus, which consists of histologically and functionally distinct subunits, primarily modulates vegetative symptoms in major depressive disorder (MDD). Sex differences in MDD have been well-documented in terms of illness incidence rates and symptom profiles. However, few studies have explored subunit-level and sex-specific anatomic differences in the hypothalamus in MDD compared to healthy controls (HCs). High-resolution 3D T1-weighted images were obtained from 133 treatment-naïve patients with MDD and 130 age-, sex-, education years-, and handedness-matched HCs. MRI data were preprocessed and segmented into ten bilateral hypothalamic subunits with FreeSurfer software. We tested for both common and sex-specific patterns of hypothalamic anatomic differences in MDD. Regardless of sex, patients with MDD showed significantly smaller volumes in the left anterior-inferior subunit (a-iHyp) and larger volumes in the right posterior subunit (posHyp). The volumes of the left a-iHyp were negatively correlated with sleep disturbance scores in the MDD group. A significant sex-by-diagnosis interaction was observed in the right whole hypothalamus, and subsequent post-hoc analyses revealed that males with MDD showed significantly larger volumes, while females with MDD showed significantly smaller volumes relative to their sex-matched HCs. Common differences in MDD were found in the left anterior-inferior and right posterior hypothalamus that are involved in regulating circadian rhythms and reward, while sex-specific differences in MDD were observed in the right whole hypothalamus. These findings enhance our understanding of distinct hypothalamic subunit related to MDD and shed light on the neurobiology underlying sex-related variations in MDD.

The Hippo signalling cascade is an evolutionarily conserved pathway critical for the development of numerous organ systems and is required for the development of many parts of the mammalian nervous system, including the cerebellum. The Hippo pathway converges, via the nuclear YAP/TAZ co-transcription factors, on transcription factors of the TEA Domain (TEAD) family (TEAD1-4) and promotes the expression of pro-proliferative genes. Despite the importance of TEAD function, our understanding of spatial and temporal expression of this family is limited, as is our understanding of which TEAD family members regulate Hippo-dependent organ development. Here, we focus on TEAD1 and how this factor contributes to postnatal murine cerebellar development. We find expression of TEAD1 within cerebellar progenitor cells and glial cells, including astrocytes and Bergmann glia, as well as by some interneurons within the granular layer. The importance of TEAD1 expression for cerebellar development was investigated using a conditional ablation approach, which revealed a range of developmental deficits in Tead1 mutants, including an underdeveloped cerebellum, morphological defects in Bergmann Glia and Purkinje Neurons, as well as granule neuron migration defects. Collectively, these findings suggest a major role for TEAD1 as an effector of the Hippo pathway during cerebellar development.

Evidence shows that ultra-high dose-rate FLASH-radiotherapy (FLASH-RT) provides relative protection against normal tissue complications and functional decrements in the irradiated brain. Past work has shown that radiation-induced cognitive impairment, neuroinflammation and reduced structural complexity ofgranule cell neurons were not observed to the same extent after FLASH-RT (> MGy/s) compared to conventional dose-rate (CONV, 0.1 Gy/s) delivery. In this study, we explored the sensitivity of hippocampal CA1 and medial prefrontal cortex (mPFC) pyramidal neurons to cranial irradiation and dose-rate modulation using electron and confocal microscopy. Neuron ultrastructural analyses by electron microscopy after 10 Gy FLASH- or CONV-RT exposures indicated that irradiation had little impact on dendritic complexity and synapse density in the CA1, but did increase the length and head diameter of smaller non-perforated synapses. Similarly, irradiation caused no change in mPFC prelimbic/infralimbic axospinous synapse density, but reductions in non-perforated synapse diameters. While irradiation resulted in thinner myelin sheaths compared to controls, none of these metrics were dose-rate sensitive. Analysis of fluorescently labeled CA1 neurons revealed no radiation-induced or dose-rate-dependent changes in overall dendritic complexity or spine density, in contrast to our past analysis of granule cell neurons. Super-resolution confocal microscopy following a clinical dosing paradigm (3 × 10 Gy) showed significant reductions in excitatory vesicular glutamate transporter 1 and inhibitory vesicular GABA transporter puncta density within the CA1 that were largely dose-rate independent. Collectively, these data reveal that, compared to granule cell neurons, CA1 and mPFC neurons are relatively more radioresistant irrespective of radiation dose-rate.

This study aimed to better understand the neuroanatomical correlates of decision-making strategies, particularly focusing on win-stay and lose-shift behaviours, using voxel-based morphometry (VBM) in a large cohort of healthy adults. Participants completed a forced-choice card-guessing task designed to elicit behavioural responses to rewards and losses. Using this task, we investigated the relationship between win-stay and lose-shift behaviour and both grey matter volume (GMV) and white matter volume (WMV). The frequency of win-stay and lose-shift behaviours was calculated for each participant and entered into VBM analyses alongside GMV and WMV measures. Our results revealed that increased lose-shift behaviour was associated with reduced GMV in key brain regions, comprising of the left superior temporal gyrus, right middle temporal gyrus, and the bilateral superior lateral occipital cortices. Interestingly, no significant associations were found between GMV or WMV, and win-stay behaviour. These results suggest that specific regions within the temporal and occipital lobes may be involved in modulating decision-making strategies following negative outcomes. Further analyses revealed that increased lose-shift behaviour was also associated with increased WMV in the left superior temporal gyrus. The absence of significant findings in relation to win-stay behaviour and the differential involvement of brain structures in lose-shift responses indicate that decision-making in the face of losses may involve distinct neuroanatomical mechanisms compared to decision-making following wins. This study advances our understanding of the structural brain correlates linked to decision-making strategies and highlights the complexity of brain-behaviour relationships in choice behaviour.

The influence of regional brain vasculature on resting-state fMRI BOLD signals is well documented. However, the role of brain vasculature is often overlooked in functional connectivity research. In the present report, utilizing publicly available whole-brain vasculature data in the mouse, we investigate the relationship between functional connectivity and brain vasculature. This is done by assessing interregional variations in vasculature through a novel metric termed vascular similarity. First, we identify features to describe the regional vasculature. Then, we employ multiple linear regression models to predict functional connectivity, incorporating vascular similarity alongside metrics from structural connectivity and spatial topology. Our findings reveal a significant correlation between functional connectivity strength and regional vasculature similarity, especially in anesthetized mice. We also show that multiple linear regression models of functional connectivity using standard predictors are improved by including vascular similarity. We perform this analysis at the cerebrum and whole-brain levels using data from both male and female mice. Our findings regarding the relation between functional connectivity and the underlying vascular anatomy may enhance our understanding of functional connectivity based on fMRI and provide insights into its disruption in neurological disorders.

Synapse formation is a critical step in neuronal development. Current knowledge is largely based on altricial rodents where synapse formation and maturation proceed largely postnatally. In precocially born mammals such as guinea pig presynapse and spine formation start well before birth. Here, we analysed the developmental expression of proteins associated with synapse formation and maturation together with the development of basal dendritic spines of pyramidal neurons of visual and somatosensory cortex of the pig, an emerging translational model for human neurodegenerative disorders. A total of 23 selected proteins was quantified with Western blots. Most were detectable from midgestation embryonal day (E) 65 onwards. About half reached the expression level seen at postnatal day (P) 90 pig already two weeks before birth (gestation 114 days) in somatosensory, albeit not yet in visual cortex. For instance, major molecular components of synaptic plasticity such as GluN2B, CamKIIα, α-actinin-2, synaptopodin and T286 phosphorylated CamKIIα were expressed at E100 in somatosensory cortex. Dendritic spine type quantification with DiI-labeled material revealed an increase of total dendritic protrusions from E70 onwards. The increase was steepest in somatosensory cortex which had, at E110, a proportion of mushroom spines equal to the proportion present at P90. Together, matching the ungulate life history, a rapid development of functional synaptic connectivity in prenatal somatosensory cortex serves the somatomotor abilities essentially required by the newborn nest-fledgling.