Brain最新文献

Extensive neuroimaging research in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) has identified brain atrophy as a disease phenotype. While it is also related to a complex genetic architecture, the transition from genetic risk factors to brain vulnerabilities remains unclear. Using a population-based approach, we examined the associations between epilepsy-related polygenic risk for HS (PRS-HS) and brain structure in healthy developing children, assessed their relation to brain network architecture, and evaluated its correspondence with case-control findings in TLE-HS diagnosed patients relative to healthy individuals. We used genome-wide genotyping and structural T1-weighted MRI of 3826 neurotypical children from the Adolescent Brain Cognitive Development (ABCD) study. Surface-based linear models related PRS-HS to cortical thickness measures, and subsequently contextualized findings with structural and functional network architecture based on epicentre mapping approaches. Imaging-genetic associations were then correlated to atrophy and disease epicentres in 785 patients with TLE-HS relative to 1512 healthy controls aggregated across multiple sites. Higher PRS-HS was associated with decreases in cortical thickness across temporo-parietal as well as fronto-central regions of neurotypical children. These imaging-genetic effects were anchored to the connectivity profiles of distinct functional and structural epicentres. Compared with disease-related alterations from a separate epilepsy cohort, regional and network correlates of PRS-HS strongly mirrored cortical atrophy and disease epicentres observed in patients with TLE-HS and were highly replicable across different studies. Findings were consistent when using statistical models controlling for spatial autocorrelations and robust to variations in analytic methods. Capitalizing on recent imaging-genetic initiatives, our study provides novel insights into the genetic underpinnings of structural alterations in TLE-HS, revealing common morphological and network pathways between genetic vulnerability and disease mechanisms. These signatures offer a foundation for early risk stratification and personalized interventions targeting genetic profiles in epilepsy.

TOC Summary R. Mark Richardson argues that, in an era where sensing-enabled devices can provide effective therapy when applied to appropriate seizure networks, treating thalamic implantation as research by default may be overly conservative. He views hypothesis-driven thalamic SEEG as indispensable for optimizing neuromodulation strategies.

Learning is a fundamental aspect of human behaviour and is essential for adapting to new environments and situations. The ventral tegmental area is a critical brain area containing neurons that release dopamine to signal reward, drive learning and bias decision-making. Human data on the ventral tegmental area's effects on cognition are scarce, and no studies have causally manipulated the human ventral tegmental area. Here we studied a unique group of patients who had deep brain stimulation surgery in the ventral tegmental area to improve pain due to trigeminal autonomic cephalalgias refractory to medical therapy. In this study, we asked how deep brain stimulation, which aimed to inhibit the ventral tegmental area, affected reward-related learning and decision-making. Patients performed a reversal learning task while their deep brain stimulation was switched on versus off, in a powerful within-subject design. In the task, patients learned to choose between two options to win money, based on previous outcomes, but also made post-decision bets based on whether they thought they were likely to win. This allowed us also to investigate the effect of electrical stimulation within the ventral tegmental area on betting behaviour. We found that stimulation did not affect learning in this group of patients but led to a more strategic betting behaviour. First, stimulation reduced the bias whereby healthy people tend to bet similarly to the previous trial. Second, when on stimulation, bets were more strongly linked to the actual value of the choice. The data indicate that disrupting ventral tegmental area signals by electrical stimulation reduces the perseverative betting bias, permitting more strategic decision-making. We interpret this to mean that mesolimbic dopaminergic signals in humans may be important in producing persistence of reward-driven behaviours over time.

Mutations in the SNCA gene encoding α-synuclein (α-syn) underlie familial early-onset Parkinson's disease (PD). Pathological α-syn deposition may commence decades prior to the emergence of cardinal motor symptoms. Long-term investigation of brain and behavioral development in an SNCA-A53T transgenic macaque model offers critical insights into PD progression. In this study, we systematically characterized SNCA-A53T transgenic rhesus monkeys through multimodal assessments. Our results showed that these transgenic monkeys exhibited phosphorylated α-syn aggregation patterns and dopaminergic degeneration resembling PD patients. Progressive motor and cognitive deficits were observed in transgenic monkeys with aging. Polysomnographic analysis revealed REM sleep behavior disorder manifestations in transgenic animals. Four-year longitudinal MRI tracking demonstrated abnormal developmental patterns of cortical surface area alongside thickness and volume alterations. Single-cell transcriptome revealed that astrocyte-specific gene dysregulation and cell loss contribute to brain atrophy in transgenic monkeys. Cortical and subcortical gray matter regions showing volume reduction were functionally associated with behavioral deficits and differentiated transgenic animals from wild-type controls. Collectively, this comprehensive study provides evidence that SNCA-A53T transgenic monkeys recapitulate PD pathophysiology while demonstrating the utility of longitudinal monitoring in genetically engineered nonhuman primates for tracking neurodegenerative disease progression.