2. Age- and gender-related selleck compound signal variability The growth and development of ICNs have been observed through infancy into adulthood [9,24-26]. In addition, group comparisons of functional connectivity between young adults and the elderly in two nodes of the DMN have demonstrated age-associated disconnection of anterior to posterior regions [27]. Also, a recent publication of a large multicenter cohort analyzed with both seed-based voxel-wise methods and ICA has demonstrated a significant age and gender effect on connectivity [28]. These studies suggest that there is a significant amount of change within ICN throughout the lifespan. Work from our lab recently demonstrated that the age effect on ICNs is accelerated in AD, further emphasizing the importance of understanding and accounting for the effect of age on TF-fMRI investigations of neurodegenerative illnesses [29].

3. Number of independent components in independent component analysis Theoretically, the total or maximum number of ICNs is not deterministic in every human brain; therefore, setting the total number of independent components (or networks) that need to be extracted using ICA is ambiguous. If the number of independent components is set lower than the total number of ICNs in the brain, multiple ICNs might be fused together and not be well separated. On the other hand, specifying a larger number of independent components may split the existing ICNs into two or more subsystems (as shown by different ICNs detected by different colors in Figures ?Figures1b1b and ?and2b).2b).

While this remains an open question, recent studies have suggested that 20 independent components may be a reasonable assumption Carfilzomib [10]. An additional point to note while looking at the networks from an ICA is that some components may contain artifacts that can be used to denoise subsequent analyses [30]. B. Task-free functional magnetic resonance imaging Alzheimer’s disease studies As mentioned above, rs-fMRI or TF-fMRI is becoming increasingly popular in the field of AD biomarkers. In this section, we present various published studies that have used the methods discussed in section A. We have broadly categorized the various TF-fMRI studies in AD and mild cognitive impairment (MCI) (prodromal stage of AD) into six groups and discuss the current state of knowledge in each of these. 1.

Network-based studies in Alzheimer’s disease Functional imaging studies using positron emission tomography (PET) as well as fMRI have repeatedly observed the presence of deactivation in consistent brain regions in response to a task. This observation, along with the fact that the same regions have higher blood flow and oxygen consumption at rest, led to the conclusion that specific this regions have higher baseline activity that is turned off during any task-induced state [31].