Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease.

Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate local neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex several years before amyloid deposition. We find the same early cingulate FC disruption and neuronal hyperactivity in AppNL-F mice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astrocytic calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral disruptions. In conclusion, we show that astrocytes mediate initial features of AD and drive clinically relevant phenotypes.

Posterior Intraparietal Sulcus Mediates Detection of Salient Stimuli Outside the Endogenous Focus of Attention.

Visual consciousness is shaped by the interplay between endogenous selection and exogenous capture. If stimulus saliency is aligned with a subject's attentional priorities, endogenous selection will be facilitated. In case of a misalignment, endogenous selection may be compromised as attentional capture is a strong and automatic process. We manipulated task-congruent versus -incongruent saliency in a functional magnetic resonance imaging change-detection task and analyzed brain activity patterns in the cortex surrounding the intraparietal sulcus (IPS) within the Julich-Brain probabilistic cytoarchitectonic mapping reference frame. We predicted that exogenous effects would be seen mainly in the posterior regions of the IPS (hIP4-hIP7-hIP8), whereas a conflict between endogenous and exogenous orienting would elicit activity from more anterior cytoarchitectonic areas (hIP1-hIP2-hIP3). Contrary to our hypothesis, a conflict between endogenous and exogenous orienting had an effect early in the IPS (mainly in hIP7 and hIP8). This is strong evidence for an endogenous component in hIP7/8 responses to salient stimuli beyond effects of attentional bottom-up sweep. Our results suggest that hIP7 and hIP8 are implicated in the individuation of attended locations based on saliency as well as endogenous instructions.

Reproducibility of graph measures at the subject level using resting-state fMRI.

INTRODUCTION: Graph metrics have been proposed as potential biomarkers for diagnosis in clinical work. However, before it can be applied in a clinical setting, their reproducibility should be evaluated. METHODS: This study systematically investigated the effect of two denoising pipelines and different whole-brain network constructions on reproducibility of subject-specific graph measures. We used the multi-session fMRI dataset from the Brain Genomics Superstruct Project consisting of 69 healthy young adults. RESULTS: In binary networks, the test-retest variability for global measures was large at low density irrespective of the denoising strategy or the type of correlation. Weighted networks showed very low test-retest values (and thus a good reproducibility) for global graph measures irrespective of the strategy used. Comparing the test-retest values for different strategies, there were significant main effects of the type of correlation (Pearson correlation vs. partial correlation), the (partial) correlation value (absolute vs. positive vs. negative), and weight calculation (based on the raw (partial) correlation values vs. based on transformed Z-values). There was also a significant interaction effect between type of correlation and weight calculation. Similarly as for the binary networks, there was no main effect of the denoising pipeline. CONCLUSION: Our results demonstrated that normalized global graph measures based on a weighted network using the absolute (partial) correlation as weight were reproducible. The denoising pipeline and the granularity of the whole-brain parcellation used to define the nodes were not critical for the reproducibility of normalized graph measures.

Representation of associative and affective semantic similarity of abstract words in the lateral temporal perisylvian language regions.

The examination of semantic cognition has traditionally identified word concreteness as well as valence as two of the principal dimensions in the representation of conceptual knowledge. More recently, corpus-based vector space models as well as graph-theoretical analysis of large-scale task-related behavioural responses have revolutionized our insight into how the meaning of words is structured. In this fMRI study, we apply representational similarity analysis to investigate the conceptual representation of abstract words. Brain activity patterns were related to a cued-association based graph as well as to a vector-based co-occurrence model of word meaning. Twenty-six subjects (19 females and 7 males) performed an overt repetition task during fMRI. First, we performed a searchlight classification procedure to identify regions where activity is discriminable between abstract and concrete words. These regions were left inferior frontal gyrus, the upper and lower bank of the superior temporal sulcus bilaterally, posterior middle temporal gyrus and left fusiform gyrus. Representational Similarity Analysis demonstrated that for abstract words, the similarity of activity patterns in the cortex surrounding the superior temporal sulcus bilaterally and in the left anterior superior temporal gyrus reflects the similarity in word meaning. These effects were strongest for semantic similarity derived from the cued association-based graph and for affective similarity derived from either of the two models. The latter effect was mainly driven by positive valence words. This research highlights the close neurobiological link between the information structure of abstract and affective word content and the similarity in activity pattern in the lateral and anterior temporal language system.