Brain Communications
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Epileptic discharges initiate from brain areas with elevated accumulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors Abstract Presurgical identification of the epileptogenic zone is a critical determinant of seizure control following surgical resection in epilepsy. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor is a major component of neurotransmission. Although elevated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor levels are observed in surgically resected brain areas of patients with epilepsy, it remains unclear whether increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated currents initiate epileptic discharges. We have recently developed the first PET tracer for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, [11C]K-2, to visualize and quantify the density of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in living human brains. Here, we detected elevated [11C]K-2 uptake in the epileptogenic temporal lobe of patients with mesial temporal lobe epilepsy. Brain areas with high [11C]K-2 uptake are closely colocalized with the location of equivalent current dipoles estimated by magnetoencephalography or with seizure onset zones detected by intracranial electroencephalogram. These results suggest that epileptic discharges initiate from brain areas with increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, providing a biological basis for epileptic discharges and an additional non-invasive option to identify the epileptogenic zone in patients with mesial temporal lobe epilepsy.
Brain Communications - Tập 4 Số 2 - 2022
<i>APOE</i> ε4 alters associations between docosahexaenoic acid and preclinical markers of Alzheimer’s disease Abstract
Docosahexaenoic acid is the main long-chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30−40% of fatty acids in the grey matter of the human cortex. Although the influence of docosahexaenoic acid on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic Alzheimer’s disease. We investigated the cross-sectional relationship between docosahexaenoic acid levels and the major structural and cognitive markers of preclinical Alzheimer’s disease, namely hippocampal volume, entorhinal volume and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum docosahexaenoic acid (DHA, including lysophosphatidylcholine DHA) and APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. APOE genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in non APOΕ ε4 carriers. APOE also interacted with serum lysophosphatidylcholine DHA to predict hippocampal volume. After testing interactions between DHA and APOE on brain volume, we investigated whether DHA and APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for Alzheimer’s disease in an independent population of APOE genotyped adults (n = 46). APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in APOE ε4 carriers only. This exploratory analysis suggests that interventions aiming to increase DHA blood levels to protect against cognitive decline should consider APOE ε4 carrier status. Future work should focus on replicating our initial findings and establishing whether a specific dose of supplementary DHA, at a particular time in the preclinical disease course can have a positive impact on Alzheimer’s disease progression in APOE ε4 carriers.
Brain Communications - Tập 3 Số 2 - 2021
Exploring white matter functional networks in children with attention-deficit/hyperactivity disorder Abstract Attention-deficit/hyperactivity disorder has been identified to involve the impairment of large-scale functional networks within grey matter, and recent studies have suggested that white matter, which also encodes neural activity, can manifest intrinsic functional organization similar to that of grey matter. However, the alterations in white matter functional networks in attention-deficit/hyperactivity disorder remain unknown. We recruited a total of 99 children, including 66 drug-naive patients and 33 typically developing controls aged from 6 to 14, to characterize the alterations in functional networks within white matter in drug-naive children with attention-deficit/hyperactivity disorder. Using clustering analysis, resting-state functional MRI data in the white matter were parsed into different networks. Intrinsic activity within each network and connectivity between networks and the associations between network activity strength and clinical symptoms were assessed. We identified eight distinct white matter functional networks: the default mode network, the somatomotor network, the dorsal attention network, the ventral attention network, the visual network, the deep frontoparietal network, the deep frontal network and the inferior corticospinal-posterior cerebellum network. The default mode, somatomotor, dorsal attention and ventral attention networks showed lower spontaneous neural activity in patients. In particular, the default mode network and the somatomotor network largely showed higher connectivity with other networks, which correlated with more severe hyperactive behaviour, while the dorsal and ventral attention networks mainly had lower connectivity with other networks, which correlated with poor attention performance. In conclusion, there are two distinct patterns of white matter functional networks in children with attention-deficit/hyperactivity disorder, with one being the hyperactivity-related hot networks including default mode network and somatomotor network and the other being inattention-related cold networks including dorsal attention and ventral attention network. These results extended upon our understanding of brain functional networks in attention-deficit/hyperactivity disorder from the perspective of white matter dysfunction.
Brain Communications - Tập 2 Số 2 - 2020
Evaluation of [18F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies Abstract
Tau aggregates represent a key pathologic feature of Alzheimer’s disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer’s disease tauopathies. The novel tau PET tracer, [18F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer’s disease and non-Alzheimer’s disease tauopathies. To assess the ability of [18F]PI-2620 to detect regional tau burden in non-Alzheimer’s disease tauopathies compared with Alzheimer’s disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1) or Alzheimer’s disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid β assessment and [18F]PI-2620 PET (Image acquisition at 60–90 min post-injection). Cortical and subcortical tau accumulations were assessed by calculating standardized uptake value ratios using [18F]PI-2620 PET. For pathologic validation, tau pathology was assessed using tau immunohistochemistry and compared with [18F]PI-2620 retention in an autopsied case of corticobasal degeneration. In Alzheimer’s disease, focal retention of [18F]PI-2620 was evident in the temporal and parietal lobes, precuneus, and cingulate cortex. Standardized uptake value ratio analyses revealed that patients with non-Alzheimer’s disease tauopathies had elevated [18F]PI-2620 uptake only in the globus pallidus, as compared to patients with Alzheimer’s disease, but not healthy controls. A head-to-head comparison of [18F]PI-2620 and [18F]PM-PBB3, another tau PET probe for possibly visualizing the four-repeat tau pathogenesis in non-Alzheimer’s disease, revealed different retention patterns in one subject with progressive supranuclear palsy. Imaging-pathology correlation analysis of the autopsied patient with corticobasal degeneration revealed no significant correlation between [18F]PI-2620 retention in vivo. High [18F]PI-2620 uptake at 60–90 min post-injection in the globus pallidus may be a sign of neurodegeneration in four-repeat tauopathy, but not necessarily practical for diagnosis of non-Alzheimer’s disease tauopathies. Collectively, this tracer is a promising tool to detect Alzheimer’s disease-tau aggregation. However, late acquisition PET images of [18F]PI-2620 may have limited utility for reliable detection of four-repeat tauopathy because of lack of correlation between post-mortem tau pathology and different retention pattern than the non-Alzheimer’s disease-detectable tau radiotracer, [18F]PM-PBB3. A recent study reported that [18F]PI-2620 tracer kinetics curves in four-repeat tauopathies peak earlier (within 30 min) than Alzheimer’s disease; therefore, further studies are needed to determine appropriate PET acquisition times that depend on the respective interest regions and diseases.
Brain Communications - Tập 3 Số 4 - 2021
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