Alzheimer's disease (AD) is associated not only with regional gray matter damages, but also with abnormalities in functional integration between brain regions. Here, we employed resting-state functional magnetic resonance imaging data and voxel-based graph-theory analysis to systematically investigate intrinsic functional connectivity patterns of whole-brain networks in 32 AD patients and 38 healthy controls (HCs). We found that AD selectively targeted highly connected hub regions (in terms of nodal functional connectivity strength) of brain networks, involving the medial and lateral prefrontal and parietal cortices, insula, and thalamus. This impairment was connectivity distance-dependent (Euclidean), with the most prominent disruptions appearing in the long-range connections (e.g., 100-130 mm). Moreover, AD also disrupted functional connections within the default-mode, salience and executive-control modules, and connections between the salience and executive-control modules. These disruptions of hub connectivity and modular integrity significantly correlated with the patients' cognitive performance. Finally, the nodal connectivity strength in the posteromedial cortex exhibited a highly discriminative power in distinguishing individuals with AD from HCs. Taken together, our results emphasize AD-related degeneration of specific brain hubs, thus providing novel insights into the pathophysiological mechanisms of connectivity dysfunction in AD and suggesting the potential of using network hub connectivity as a diagnostic biomarker.

Human brain functional networks are topologically organized with nontrivial connectivity characteristics such as small-worldness and densely linked hubs to support highly segregated and integrated information processing. However, how they emerge and change at very early developmental phases remains poorly understood. Here, we used resting-state functional MRI and voxel-based graph theory analysis to systematically investigate the topological organization of whole-brain networks in 40 infants aged around 31 to 42 postmenstrual weeks. The functional connectivity strength and heterogeneity increased significantly in primary motor, somatosensory, visual, and auditory regions, but much less in high-order default-mode and executive-control regions. The hub and rich-club structures in primary regions were already present at around 31 postmenstrual weeks and exhibited remarkable expansions with age, accompanied by increased local clustering and shortest path length, indicating a transition from a relatively random to a more organized configuration. Moreover, multivariate pattern analysis using support vector regression revealed that individual brain maturity of preterm babies could be predicted by the network connectivity patterns. Collectively, we highlighted a gradually enhanced functional network segregation manner in the third trimester, which is primarily driven by the rapid increases of functional connectivity of the primary regions, providing crucial insights into the topological development patterns prior to birth.

In a series of experiments, the authors investigated whether naming latencies for homophones (e.g., /nlambdan/) are a function of specific-word frequency (i.e., the frequency of nun) or a function of cumulative-homophone frequency (i.e., the sum of the frequencies of nun and none). Specific-word but not cumulative-homophone frequency affected picture-naming latencies. This result was obtained in 2 languages (English and Chinese). An analogous finding was obtained in a translation task, where bilingual speakers produced the English names of visually presented Spanish words. Control experiments ruled out that these results are an artifact of orthographic or articulatory factors, or of visual recognition. The results argue against the hypothesis that homophones share a common word-form representation, and support instead a model in which homophones have fully independent representations.

Conceptual processing is a crucial brain function for humans. Past research using neuropsychological and task-based functional brainimaging paradigms indicates that widely distributed brain regions are related to conceptual processing. Here, we explore the potential contribution of intrinsic or spontaneous brain activity to conceptual processing by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals can account for individual differences in the conceptual processing efficiencies of healthy individuals. We acquired rs-fMRI and behavioral data on object conceptual processing tasks. We found that the regional amplitude of spontaneous low-frequency fluctuations in the blood oxygen level-dependent signal in the left (posterior) middle temporal gyrus (LMTG) was highly correlated with participants' semantic processing efficiency. Furthermore, the strength of the functional connectivity between the LMTG and a series of brain regions-the left inferior frontal gyrus, bilateral anterior temporal lobe, bilateral medial temporal lobe, posterior cingulate gyrus, and ventromedial and dorsomedial prefrontal cortices-also significantly predicted conceptual behavior. The regional amplitude of low-frequency fluctuations and functionally relevant connectivity strengths of LMTG together accounted for 74% of individual variance in object conceptual performance. This semantic network, with the LMTG as its core component, largely overlaps with the regions reported in previous conceptual/semantic task-based fMRI studies. We conclude that the intrinsic or spontaneous activity of the human brain reflects the processing efficiency of the semantic system.

Widely distributed brain regions in temporal, parietal and frontal cortex have been found to be involved in semantic processing, but the anatomical connections supporting the semantic system are not well understood. In a group of 76 right-handed brain-damaged patients, we tested the relationship between the integrity of major white matter tracts and the presence of semantic deficits. The integrity of white matter tracts was measured by percentage of lesion voxels obtained in structural imaging and mean fractional anisotropy values obtained in diffusion tensor imaging. Semantic deficits were assessed by jointly considering the performance on three semantic tasks that vary in the modalities of input (visual and auditory stimuli) and output (oral naming and associative judgement). We found that the lesion volume and fractional anisotropy value of the left inferior fronto-occipital fasciculus, left anterior thalamic radiation, and left uncinate fasciculus significantly correlated with severity of impairment in all three semantic tasks. These associations remained significant even when we controlled for a wide range of potential confounding variables, including overall cognitive state, whole lesion volume, or type of brain damage. The effects of these three white matter tracts could not be explained by potential involvement of relevant grey matter, and were (relatively) specific to object semantic processing, as no correlation with performance on non-object semantic control tasks (oral repetition and number processing tasks) was observed. These results underscore the causal role of left inferior fronto-occipital fasciculus, left anterior thalamic radiation, and left uncinate fasciculus in semantic processing, providing direct evidence for (part of) the anatomical skeleton of the semantic network.

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