A Linear Structural Equation Model for Covert Verb Generation Based on Independent Component Analysis of fMRI Data from Children and Adolescents

Human language is a complex and protean cognitive ability. Young children, following well defined developmental patterns learn language rapidly and effortlessly producing full sentences by the age of 3 years. However, the language circuitry continues to undergo significant neuroplastic changes extending well into teenage years. Evidence suggests that the developing brain adheres to two rudimentary principles of functional organization: functional integration and functional specialization. At a neurobiological level, this distinction can be identified with progressive specialization or focalization reflecting consolidation and synaptic reinforcement of a network (Lenneberg, 1967; Muller et al., 1998; Berl et al., 2006). In this paper, we used group independent component analysis and linear structural equation modeling (McIntosh and Gonzalez-Lima, 1994; Karunanayaka et al., 2007) to tease out the developmental trajectories of the language circuitry based on fMRI data from 336 children ages 5–18 years performing a blocked, covert verb generation task. The results are analyzed and presented in the framework of theoretical models for neurocognitive brain development. This study highlights the advantages of combining both modular and connectionist approaches to cognitive functions; from a methodological perspective, it demonstrates the feasibility of combining data-driven and hypothesis driven techniques to investigate the developmental shifts in the semantic network

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease

Olfactory impairment is associated with prodromal Alzheimer’s disease (AD) and is a risk factor for the development of dementia. AD pathology is known to disrupt brain regions instrumental in olfactory information processing, such as the primary olfactory cortex (POC), the hippocampus, and other temporal lobe structures. This selective vulnerability suggests that the functional connectivity (FC) between the olfactory network (ON), consisting of the POC, insula and orbital frontal cortex (OFC) (Tobia et al., 2016), and the hippocampus may be impaired in early stage AD. Yet, the development trajectory of this potential FC impairment remains unclear. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate FC changes between the ON and hippocampus in four groups: aged-matched cognitively normal (CN), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD. FC was calculated using low frequency fMRI signal fluctuations in the ON and hippocampus (Tobia et al., 2016). We found that the FC between the ON and the right hippocampus became progressively disrupted across disease states, with significant differences between EMCI and LMCI groups. Additionally, there were no significant differences in gray matter hippocampal volumes between EMCI and LMCI groups. Lastly, the FC between the ON and hippocampus was significantly correlated with neuropsychological test scores, suggesting that it is related to cognition in a meaningful way. These findings provide the first in vivo evidence for the involvement of FC between the ON and hippocampus in AD pathology. Results suggest that functional connectivity (FC) between the olfactory network (ON) and hippocampus may be a sensitive marker for Alzheimer’s disease (AD) progression, preceding gray matter volume loss

Lexical-Semantic Search Under Different Covert Verbal Fluency Tasks: An fMRI Study

Background: Verbal fluency is a measure of cognitive flexibility and word search strategies that is widely used to characterize impaired cognitive function. Despite the wealth of research on identifying and characterizing distinct aspects of verbal fluency, the anatomic and functional substrates of retrieval-related search and post-retrieval control processes still have not been fully elucidated.Methods: Twenty-one native English-speaking, healthy, right-handed, adult volunteers (mean age = 31 years; range = 21–45 years; 9 F) took part in a block-design functional Magnetic Resonance Imaging (fMRI) study of free recall, covert word generation tasks when guided by phonemic (P), semantic-category (C), and context-based fill-in–the-blank sentence completion (S) cues. General linear model (GLM), Independent Component Analysis (ICA), and psychophysiological interaction (PPI) were used to further characterize the neural substrate of verbal fluency as a function of retrieval cue type.Results: Common localized activations across P, C, and S tasks occurred in the bilateral superior and left inferior frontal gyrus, left anterior cingulate cortex, bilateral supplementary motor area (SMA), and left insula. Differential task activations were centered in the occipital, temporal and parietal regions as well as the thalamus and cerebellum. The context-based fluency task, i.e., the S task, elicited higher differential brain activity in a lateralized frontal-temporal network typically engaged in complex language processing. P and C tasks elicited activation in limited pathways mainly within the left frontal regions. ICA and PPI results of the S task suggested that brain regions distributed across both hemispheres, extending beyond classical language areas, are recruited for lexical-semantic access and retrieval during sentence completion.Conclusion: Study results support the hypothesis of overlapping, as well as distinct, neural networks for covert word generation when guided by different linguistic cues. The increased demand on word retrieval is met by the concurrent recruitment of classical as well as non-classical language-related brain regions forming a large cognitive neural network. The retrieval-related search and post-retrieval control processes that subserve verbal fluency, therefore, reverberates across distinct functional networks as determined by respective task demands