Central executive network in young people with familial risk for psychosis — The Oulu Brain and Mind Study
Introduction
The function of large-scale neurocognitive networks is thought to provide important insights into psychiatric and neurological disorders (Bressler and Menon, 2010, Menon, 2011). One of these networks is called the central executive network (CEN) that is localized in fronto-parietal regions, including the dorsolateral prefrontal cortex and lateral posterior parietal cortex (Seeley et al., 2007).
The CEN is crucial for the attentional system (Norman and Shallice, 1986). It contributes to many high-level neurocognitive functions such as working memory, planning, problem solving and decision making (Menon, 2011, Petrides, 2000, Koechlin and Summerfield, 2007, Miller and Cohen, 2001, Müller and Knight, 2006). The CEN plays an important role in strategy selection (Collette and Van der Linden, 2002), verbal fluency, dual-task performance, switching of retrieval strategy, inhibiting irrelevant effects, holding and manipulating information in long-term memory (Baddeley, 1996) and updating processes (Morris and Jones, 1990).
The CEN has strong connectivity to the default mode network, and to another major cognitive control network: the salience network (Christoff et al., 2009, Menon and Uddin, 2010, Palaniyappan et al., 2011). The default mode network is activated while resting, while the CEN and salience networks are activated while conducting a task. The CEN is usually activated together with the salience network and shares function to form a neural switch that swaps brain states from non-task phase activating of the default mode network to task-phase activating CEN and salience networks and vice versa (Menon and Uddin, 2010, Sridharan et al., 2008).
Abnormal function in the CEN has been related to major psychiatric and neurological disorders, including psychosis and schizophrenia (Palaniyappan and Liddle, 2012, Henseler et al., 2009, Woodward et al., 2011, Menon et al., 2001). A few studies have suggested that functional alterations in the CEN area are evident in subjects with familial risk for psychosis (FR) (Seidman et al., 2006, Whitfield-Gabrieli et al., 2009, Repovs et al., 2011, Meda et al., 2012). Increased activation during a working memory task was found in the dorsolateral prefrontal cortex in first-degree relatives of schizophrenia or schizoaffective disorder patients (Seidman et al., 2006, Whitfield-Gabrieli et al., 2009). In other two studies siblings or first-degree relatives of individuals with schizophrenia demonstrated lower activation in the fronto-parietal and cognitive control regions during resting state functional MRI (R-fMRI) (Repovs et al., 2011, Meda et al., 2012).
In the present Oulu Brain and Mind Study the aim was to compare the central executive network (CEN) in two groups of people without psychosis: one with a history of psychotic disorder in one or both parents (the FR group), the other without any such family risk of psychosis (the control group).We applied spatial domain independent component analysis (ICA) to R-fMRI data in order to analyze 72 FR participants and 72 control participants. The two groups were well-matched as they were both drawn from the Northern Finland Birth Cohort 1986 (NFBC 1986). To the best of our knowledge this was the first R-fMRI study using a birth cohort based sample to probe the function of the CEN in subjects with FR for psychosis.
Section snippets
The Northern Finland Birth Cohort 1986 (NFBC 1986)
All participants were members of the NFBC 1986 which consists of children with an expected date of birth between July 1st 1985 and June 30th 1986 in the two northernmost provinces of Finland (Järvelin et al., 1993). Data collection was started prospectively before birth and it has continued ever since. The Ethics Committee of the Northern Ostrobothnia Hospital District in Finland has approved the study.
A field study for a subgroup of the NFBC 1986, the Oulu Brain and Mind Study, took place
Results
The demographic information from the FR group and control group is presented in Table 1. FR and control groups had the same age and gender distribution. Educational level was lower in the FR group compared to the control group, but the difference was not statistically significant (p = 0.09). There were no differences in mean IQ or level of functioning (GAF) between the two groups.
The CEN activity using 30 ICs in both groups is presented in Fig. 2. In this analysis the CEN network included areas
Discussion
This was the first birth cohort-based resting state functional MRI study of the central executive network (CEN) with young people at familial risk for psychosis (FR). We found that the activation of the CEN was significantly lower in the right inferior frontal gyrus (rIFG) in FR participants. We used two independent components analyses, both suggesting lower activation in the rIFG.
Our index subjects were young adult individuals who had not developed psychosis, but had a familial risk for
Role of funding source
This work was supported by grants from the Academy of Finland (#124257, #212818, #214273), the Finnish Medical Foundation, the NARSAD: Brain and Behavior Research Fund, the Signe and Ane Gyllenberg Foundation, Finland, the Sigrid Jusélius Foundation, the Thule Institute, University of Oulu, Finland and the UK Medical Research Council.
Contributors
Vesa Kiviniemi, Juha Nikkinen, Jouko Miettunen, Pirjo Mäki, Erika Jääskeläinen, Sari Mukkala, Anja Taanila, Irma Moilanen, Jennifer H Barnett, Peter B Jones, Graham K Murray and Juha Veijola contributed to the study design.
Vesa Kiviniemi, Juha Nikkinen, Erika Jääskeläinen, Jenni Koivukangas, Sari Mukkala, Pirjo Mäki and Juha Veijola collected the data. Tuomas Jukuri, Vesa Kiviniemi, Juha Nikkinen and Juha Parkkisenniemi analyzed the R-fMRI data. Tuomas Jukuri, Vesa Kiviniemi, and Juha Veijola
Conflict of interest
All the authors declared no conflicts of interest.
Acknowledgments
This work was supported by grants from the Academy of Finland (#124257, #212818, #214273), the Finnish Medical Foundation, the NARSAD: Brain and Behavior Research Fund, the Signe and Ane Gyllenberg Foundation, Finland, the Sigrid Jusélius Foundation, the Thule Institute, University of Oulu, Finland and the UK Medical Research Council.
We thank the participants, field study researchers and the staff in the ward 73 of the University Hospital of Oulu, Finland for their contributions to the study.
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