Brain Structure & Function最新文献

Why is it that some people seem to learn new languages faster and more easily than others? The present study investigates the neuroanatomical basis of language learning aptitude, with a focus on the multiplication pattern of the transverse temporal gyrus/gyri (TTG/TTGs) of the auditory cortex. The size and multiplication pattern of the first TTG (i.e., Heschl's gyrus; HG) and of additional posterior TTGs, when present, are highly variable both between brain hemispheres and individuals. Previous work has shown the multiplication pattern of the TTGs to be related to musical and linguistic abilities. Specifically, one study found that high language learning aptitude correlated with more TTGs in the right hemisphere, even though language functions are generally left-lateralized. In this study, we used the recently developed TASH (Toolbox for the Automated Segmentation of Heschl's Gyrus) and MCAI (Multivariate Concavity Amplitude Index) toolboxes to automatically extract structural (e.g., cortical volume, surface area, thickness) and multiplication pattern measures of the TTGs from 82 MRI scans, and related them to participants' language aptitude scores. In contrast to previous results, we found that higher language aptitude was related to fewer TTGs in the right hemisphere and to greater surface area of the first right TTG and of the second left TTG. Furthermore, more languages learned in life were associated with higher language learning aptitude, opening up questions about the structure-function relationship of the TTGs and language learning, and about how language aptitude and language learning are related.

Vocal learners, including humans and songbirds, acquire their complex vocalizations by accurately memorizing and imitating the vocal patterns of other individuals. In songbirds, the caudomedial nidopallium (NCM), considered the secondary auditory region, has been suggested to play a critical role in memorizing and recognizing the songs of tutors. However, the mechanisms by which NCM neurons encode the acoustic information of tutor song are not yet fully understood. Here, we investigate the neural representation of tutor song information in NCM neurons by examining their sensitivity to spectral changes in song structure, using electrophysiological recordings in anesthetized male zebra finches. We manipulated the acoustic structures of both tutor songs and unfamiliar conspecific songs by shifting the fundamental frequency (FF) of harmonic syllables by various frequency steps and recorded neural responses to those FF-shifted and original songs. Our results demonstrate that NCM neurons are highly sensitive to FF shifts in tutor song but much less in unfamiliar conspecific song, providing novel evidence for neural encoding of tutor song information in NCM neurons. Moreover, we find that the effects of FF shifts on neural responses depend on the direction of FF shifts. These findings suggest that NCM neurons encode detailed information of tutor song, which can serve as a tutor song template required for song learning.

Corticotropin-releasing hormone (CRH) signaling through its cognate receptors, CRHR1 and CRHR2, contributes to diverse stress-related functions in the mammalian brain. Whereas CRHR2 is predominantly expressed in choroid plexus and blood vessels, CRHR1 is abundantly expressed in neurons in discrete brain regions, including the neocortex, hippocampus and nucleus accumbens. Activation of CRHR1 influences motivated behaviors, emotional states, and learning and memory. However, it is unknown whether alterations in CRHR1 signaling contribute to aberrant motivated behaviors observed, for example, in stressful contexts. These questions require tools to manipulate CRHR1 selectively. Here we describe and validate a novel Crhr1-FlpO mouse. Using bacterial artificial chromosome (BAC) transgenesis, we engineered a transgenic mouse that expresses FlpO recombinase in CRHR1-expressing cells. We used two independent methods to assess the specificity of FlpO to CRHR1-expressing cells. First, we injected Crhr1-FlpO mice with Flp-dependent viruses expressing fluorescent reporter molecules. Additionally, we crossed the Crhr1-FlpO mouse with a transgenic Flp-dependent reporter mouse. CRHR1 and reporter molecules were identified using immunocytochemistry and visualized via confocal microscopy in several brain regions in which CRHR1 expression and function is established. Expression of Flp-dependent viral constructs was highly specific to CRHR1-expressing cells in all regions examined (over 90% co-localization). In accord, robust and specific expression of the Flp-dependent transgenic reporter was observed in a reporter mouse, recapitulating endogenous CRHR1 expression. The Crhr1-FlpO mouse enables selective genetic access to CRHR1-expressing cells within the mouse brain. When combined with Cre-lox or site-specific recombinases, the mouse facilitates intersectional manipulations of CRHR1-expressing neurons.

Healthy aging is associated with deficits in cognitive performance and brain changes, including in the cerebellum. Cerebellar communication with the cortex via closed-loop circuits through the thalamus have been established and these circuits are closely related to the functional topography of the cerebellum. In this study, we sought to elucidate relationships between cerebellar structure and function with cognition in healthy aging. We explored this relationship in 138 healthy adults (aged 35-86, 53% female) using resting-state functional connectivity MRI (fcMRI), cerebellar volume, and cognitive and motor assessments. Behavioral tasks assessed attention, processing speed, working memory, episodic memory, and motor abilities. We expected to find negative relationships between lobular volume with age, and positive relationships between specific lobular volumes with motor and cognitive behavior, respectively. We predicted lower cerebello-cortical fcMRI with increased age. Behaviorally, we expected higher cerebello-frontal and cerebello-association area fcMRI cerebellar connectivity to correlate with better behavioral performance. Correlations were conducted between cerebellar lobules I-IV, V, Crus I, Crus II, vermis VI and behavioral measures. We found lower volumes with increased age as well as both higher and lower cerebellar connectivity relationships with increased age, consistent with literature on functional connectivity and network segregation in aging. Further, we revealed unique associations between cerebellar structure and connectivity with comprehensive behavioral measures in a healthy aging population. Our findings further highlight the role of the cerebellum in aging.

Early development of the human fetal cerebral cortex involves a set of precisely coordinated molecular processes that remains rather underexplored. Previous studies indicate that the laminar identity and the molecular specification of cortical neurons driven by genetic programming, as well as associated histogenetic events begin during early fetal development. Our recent study discovered unique regional cytoarchitectonic features in the developing human frontal lobe, including migratory waves of postmitotic neurons in the dorsal frontal cortex and the "double plate" feature in orbitobasal cortex (Kopić et al. in Cells 12:231, 2023). Notably, neurons of these two cytoarchitectonic features typically express deep projection neuron (DPN) markers (TBR1, TLE4, SOX5). This paper aims to conduct an in-depth investigation of these cytoarchitectonic features at the transcriptomic level, whilst preserving spatial information. Here, we employed NanoString GeoMx^™ Digital Spatial Profiler (DSP) technology to examine gene expression differences in the transient cortical compartments of the dorsal and ventral regions of the developing frontal lobe, focusing specifically on 15 post-conceptional weeks (PCW), that is a critical period for subplate formation. We identified multiple differentially expressed genes between the transient cellular compartments of the dorsal and orbitobasal regions of the developing human frontal cortex. These new findings additionally confirm that regional patterning and specification of the prospective higher-order association prefrontal cortex emerges early in fetal development, contributing to the highly organized cortical architecture of the human brain.

Despite the widespread use of older adults (OA) as controls in movement disorder studies, the specific effects of aging on the neural control of upper and lower limb movements remain unclear. While functional MRI paradigms focusing on hand movements are widely used to investigate age-related brain changes, research on lower limb movements is limited due to technical challenges in an MRI environment. This study addressed this gap by examining both upper and lower limb movements in healthy young adults (YA) vs. OA. Sixteen YA and 20 OA, matched for sex, dominant side, and cognitive status, performed pinch grip and ankle dorsiflexion tasks, each requiring 15% of their maximum voluntary contraction. While both groups achieved the target force and exhibited similar force variability and accuracy, OA displayed distinct differences in force control dynamics, with a slower rate of force increase in the hand task and a greater rate of force decrease in the foot task. Imaging results revealed that OA exhibited more widespread activation, extending beyond brain regions typically involved in movement execution. In the hand task, OA showed increased activity in premotor and visuo-motor integration regions, as well as in the cerebellar hemispheres. During the foot task, OA engaged the cerebellar hemispheres more than YA. Collectively, results suggest that OA may recruit additional brain regions to manage motor tasks, possibly to achieve similar performance. Future longitudinal studies that track changes over time could help clarify if declines in motor performance lead to corresponding changes in brain activation.

Serotonin (5-HT) is an important neurotransmitter for cognition and neurogenesis in the dentate gyrus (DG), which occurs via movement stimulation such as physical activity. Brain 5-HT function changes secondary to aging require further investigation. We evaluated whether aged animals would present changes in the number of 5-HT neurons in regions such as the dorsal (DRN) and median (MRN) raphe nuclei and possible changes in the rate of cellular activation in the DG in response to acute running, as a reduction in 5-HT neurons could contribute to a decline in neuronal activation in the DG in response to physical activity in aged mice. This study was conducted on adult (3 months old) and aged (19 months old) male and female mice. Immunohistochemistry, microscopic analysis, and treadmill-running tests were also performed. The data revealed that in aged mice, a reduction in the number of 5-HT neurons in the DRN and MRN of male and female mice was observed. The reduction in the DRN was greater in females. Furthermore, aged animals demonstrate a lower rate of c-Fos labeling in the DG when stimulated by physical exercise. These data indicate that aging may be associated with a reduction in the number of 5-HT neurons in the DRN and MRN, which may lead to a decline in 5-HT availability in the target regions, including the DG. The reduced c-Fos expression in the DG after running in aged mice indicates a decreased response to physical activity, which is potentially linked to serotonergic deficits.

To investigate the microstructural integrity, tract volume analysis, and functional connectivity (FC) alterations of the left uncinate fasciculus (UF) in patients with amyotrophic lateral sclerosis (ALS) compared to healthy controls (HCs). Fourteen limb-onset ALS patients were recruited at baseline and ten at follow-up, along with 14 HCs. All participants underwent 3D T1-weighted, diffusion tensor imaging and kurtosis imaging (DTI/DKI), and resting-state functional MRI (rs-fMRI) using a 3 Tesla scanner with 64-channel coils. Eight metrics of diffusion, rs-FC of the left UF, and graph theory analyses were extracted. Statistical group comparisons and correlation analysis for significant diffusion metrics were also conducted. Significantly lower radial kurtosis (RK), mean kurtosis (MK), and higher DTI diffusivity metrics were observed in the left UF of ALS patients than in HCs. RK and MK were correlated with various cognitive scores, particularly executive function and visuospatial ability. The volume of the left UF was positively correlated only with RK and MK at follow-up. While rs-FC analysis did not reveal group differences, a negative functional link between the left UF and cerebellum was observed in HCs but not in patients. Graph theory analysis suggested decreased connectivity in baseline patients and potential compensatory effects during the follow-up. Our study reveals microstructural abnormalities and potential network changes in left UF. DKI metrics, especially RK and MK, may be more sensitive biomarkers than DTI metrics, particularly longitudinally. Diffusion changes appear to precede volume and functional connectivity alterations, suggesting diffusion as a potential early biomarker.

Artificial selection for specific behavioural and physical traits in domesticated animals has resulted in a wide variety of breeds. One of the most widely recognized examples of behavioural selection is the homing pigeon (Columba livia), which has undergone intense selection for fast and efficient navigation, likely resulting in significant anatomical changes to the hippocampal formation. Previous neuroanatomical comparisons between homing and other pigeon breeds yielded mixed results, but only focused on volumes. We completed a more systematic test for differences in hippocampal formation anatomy between homing and other pigeon breeds by measuring volumes, neuron numbers and neuron densities in the hippocampal formation and septum across homing pigeons and seven other breeds. Overall, we found few differences in hippocampal formation volume across breeds, but large, significant differences in neuron numbers and densities. More specifically, homing pigeons have significantly more hippocampal neurons and at higher density than most other pigeon breeds, with nearly twice as many neurons as feral pigeons. These findings suggest that neuron numbers may be an important component of homing behaviour in homing pigeons. Our data also provide the first evidence that neuronal density can be modified by artificial selection, which has significant implications for the study of domestication and interbreed variation in anatomy and behaviour.

Objective: Genetic Absence Epilepsy Rat from Strasbourg (GAERS), a rodent model genetically predisposed to absence epilepsy, serves as an experimental tool to elucidate the neuronal mechanisms underlying human absence epilepsy. This study aimed to investigate the morphological features of dendrites and dendritic spines of pyramidal neurons in somatosensory cortex and hippocampus of Wistar and GAERS rats.

Material and method: Adult male GAERS (n = 5) and control Wistar (n = 5) rats were sacrificed by transcardial perfusion and brains were removed. Brain tissues were processed by Golgi impregnation method using FD Rapid GolgiStain Kit. Coronal sections were obtained with a cryostat. Pyramidal neurons in layers V-VI of the somatosensory cortex and the CA1 region of the hippocampus were examined using a light microscope and Neurolucida 360 software. Dendrite nodes, dendrite segments (dendritic branching), dendrite terminations, total dendrite length, dendritic spine density, and dendritic spine types were analyzed.

Results: Compared to Wistar, GAERS exhibited significantly higher numbers of nodes (p = 0.0053, p = 0.0047), segments (p = 0.0036, p = 0.0036), and terminations (p = 0.0033, p = 0.0029) in the dendrites of the somatosensory cortex and the hippocampus, respectively. Furthermore, the total dendrite length (µm) (p = 0.0002, p = 0.0007) and the density of dendritic spines (1/µm) (p = 0.0168, p = 0.0120) were significantly high in GAERS compared to Wistar. When dendritic spine types were evaluated separately, stubby-type dendritic spines in the hippocampus were higher in GAERS compared to Wistar (p = 0.0045).

Conclusion: Intense synaptic connections in the somatosensory cortex and the hippocampus of genetic absence epileptic rats led to morphological alterations in the dendrites and the dendritic spines of pyramidal neurons in these regions, potentially contributing to the pathophysiology of absence seizures.