Central executive network in young people with familial risk for psychosis — The Oulu Brain and Mind Study

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Abstract

Objective

The central executive network controls and manages high-level cognitive functions. Abnormal activation in the central executive network has been related to psychosis and schizophrenia but it is not established how this applies to people with familial risk for psychosis (FR).

Methods

We conducted a resting-state functional MRI (R-fMRI) in 72 (29 males) young adults with a history of psychosis in one or both parents (FR) but without psychosis themselves, and 72 (29 males) similarly healthy control subjects without parental psychosis. Both groups in the Oulu Brain and Mind Study were drawn from the Northern Finland Birth Cohort 1986. Participants were 20–25 years old. Parental psychosis was established using the Care Register for Health Care. R-fMRI data pre-processing was conducted using independent component analysis with 30 and 70 components. A dual regression technique was used to detect between-group differences in the central executive network with p < 0.05 threshold corrected for multiple comparisons.

Results

FR participants demonstrated statistically significantly lower activity compared to control subjects in the right inferior frontal gyrus, a key area of central executive network corresponding to Brodmann areas 44 and 45, known as Broca's area. The volume of the lower activation area with 30 components was 896 mm3 and with 70 components was 1151 mm3.

Conclusion

The activity of the central executive network differed in the right inferior frontal gyrus between FR and control groups. This suggests that abnormality of the right inferior frontal gyrus may be a central part of vulnerability for psychosis.

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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