Standard MRI and DTI examination without direct medical applications This research utilizes brain imaging techniques with healthy participants only without any medical applications
Conditions
Interventions
Sponsors
Universiteit Leiden
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Participants, males and females, will be the ones with successful genotyping of COMT and DRD2, with normal or corrected to normal vision, aged between 18 and 30. Their age would not exceed thirty as the direction of genotype influence may change due to age increase (Gajewski et al., 2011).
Exclusion criteria
Exclusion criteria: Potential participants will be pre-screened for contraindications for fMRI, which include metal implants, heart arrhythmia, claustrophobia, and possible pregnancy (in females). They will additionally be pre-screened for head trauma, history of neurological or psychiatric illness and/or use of psychotropic medications. The ones with the positive results in pre-screen section will be excluded. In addition, any potential participant that uses marijuana, alcohol and recreational drug will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The main endpoint of the study is to detect sexual dimorphism in cognitive flexibility and inhibition, in carriers of A1, T and Met alleles (compared with non-carriers) of dopamine related genes polymorphisms Taq1A (rs1800497), C957T (rs6277), and Val158Met (rs4680) accordingly, in men and women. In doing so, as mostly Taq1A (rs1800497) and C957T (rs6277) mediate striatal dopamine and COMT Val158Met mediates prefrontal dopamine (Frank, Loughry, O*Reilly, 2001), via functional magnetic resonance imaging (fMRI), I will investigate how functional connectivity between brain regions, dorsal frontostriatal circuits in particular, could be influenced by sex-by-genotype interactions. In doing so, participants with successful genotyping, with respect to the afore-mentioned genes and other screening criteria mentioned in section. 7, will do the cognitive tasks mentioned in section 3., inside the MRI machine and their brains will be scanned. Regarding Val158Met (rs4680) polymorphism, it has been suggested that carriers of Val allele of this polymorphism have superior cognitive flexibility compared with carriers of Met allele (Erickson et al., 2012). As Val allele of this polymorphism is linked with higher activity of COMT which results in an increase in the rate of dopamine degradation and decreased level of dopamine in prefrontal cortex, and as higher baseline dopamine levels in brain regions involved in cognitive tasks are observed in females (Riccardi et al., 2006; 2011), I expect that carriers of Val allele, Val158Met (rs4680) polymorphism, in men have higher cognitive flexibility compared with women carrying the same allele. With reference to Taq1A (rs1800497) polymorphism, it is mentioned that carriers of A1 allele of this polymorphism compared with non-carriers (A1) are characterized more cognitive flexibility (Stelzel et al., 2013). Considering the inverse association of (lower) prefrontal dopamine levels, and (higher) striatal dopamine levels | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoint of this study is to define any differences in terms of the strength of functional connectivity in brain areas involved in cognitive flexibility and inhibition, between participants with different polymorphisms of dopamine related genes, irrespective of sex variable, in both brain intrinsic networks and fibers. Regarding brain intrinsic networks, I will use multivariate, seed-based approach to assess functional connectivity in three resting state networks that are known to be related to cognitive flexibility and inhibition (Grady,Luk, Craik, & Bialystok, 2015; Pliatsikas, & Luk, 2016) between these three groups of participants, namely in carriers of A1, T and Met alleles (compared with non-carriers) of dopamine related genes polymorphisms Taq1A (rs1800497), C957T (rs6277), and Val158Met (rs4680). The three resting state networks that are of interest in this research include: - the frontoparietal control network (FPC), including dorsolateral and inferior frontal regions and inferior parietal regions (Spreng, Sepulcre, Turner, Stevens & Schacter, 2013), - the salience network (SLN), including the anterior insula, the dorsal anterior cingulate gyrus and the supramarginal gyri (Seeley et al., 2007), - the default mode network (DMN), including the posterior cingulate gyrus, the ventromedial prefrontal cortex, the angular gyri and the parahippocampal gyri (Spreng, Mar & Kim, 2009). Regarding brain fibers, in order to understand how the micro-structure of the perisylvian network, involved in cognitive flexibility and inhibition, is different between participants - carriers of A1, T and Met alleles (compared with non-carriers) of dopamine related genes polymorphisms Taq1A (rs1800497), C957T (rs6277), and Val158Met (rs4680) - via Diffusion Tensor Imaging (DTI), I will focus on three white matter fiber tracts: - the long segment running dorsally from the frontal lobe (**Broca*s territory*) to temporal structures comprising Wern | — |
Countries
The Netherlands
Outcome results
None listed