50 A PRODH schizophrenia risk haplotype was associated with increased striatal-frontal functional connectivity, while the protective haplotype was associated with decreased striatal-frontal functional connectivity.51 A 7 single-nucleotide polymorphism (SNP) haplotype of PPPIRIB (encoding DARPP-32) was associated with functional seriously coupling and increased activation of the striatum and prefrontal cortex.52 An RGS4 variant was found to impact frontoparietal and frontotemporal coupling.53
A CACNAIC risk SNP was associated with decreased prefrontal-hippocampal Inhibitors,research,lifescience,medical connectivity.54 While some functional kinase inhibitor Regorafenib connectivity studies have employed a classic intermediate phenotype strategy, testing for regions of correlation in affected subjects as well as unaffected relatives, many studies appear to query the association of risk susceptibility gene variants with correlated regions in healthy subjects or affected patients alone, Inhibitors,research,lifescience,medical with the putative neural circuit then pending validation as an intermediate phenotype. Psycho-physiological interaction (PPI) analysis is an alternative
Inhibitors,research,lifescience,medical approach to estimating connectivity, and measures a regionally specific response in terms of an interaction between a cognitive (or sensorimotor) process and activity in another part of the brain. The supposition is that the remote region is either the source of afferents that confer functional specificity on the target region or is activated by efferents that are specifically active during the task. PPI, therefore, allows for the exploration of the effects of an independent variable Inhibitors,research,lifescience,medical (eg, genotype) on taskrelated differences in interregional connectivity.55
As Inhibitors,research,lifescience,medical a specific example, combining information about activity in the parietal region, mediating attention to a particular stimulus, and information about the stimulus, PPI aims to identify regions that respond to that stimulus when, and only when, activity in the parietal region is high. If such an interaction exists, then one might infer that the parietal area is modulating responses to the stimulus for which the area is selective. While this approach offers a deeper functional probe of network activity than simple Batimastat time series correlation analyses, it is still based on a correlation of activity and not on a directional model of activity in one region influencing activity in another. In one study, during the N-back task, DLPFC-HF coupling was identified in both patients with schizophrenia and their unaffected relatives, and associated with a ZNF804A risk allele, using seeded connectivity as well as PPI approaches.56 PPI analysis showed a reduction in task load-related modulation of coupling between the right DLPFC and bilateral HF, in patients and siblings, compared with controls.