Focusing on the 10% of ICA components with the highest BOLD-fMRI signal amplitudes revealed significant differences between the two groups in three of the component networks. One component related to task-positive networks: the IC2-EXE showed reduced signal intensity in the SZ group in the Insula, SMA, and dorsolateral section of the ACC. The IC4-VIS showed increased signal intensity in the SZ group in the fusiform gyri, in the anterior lobe, and in the occipital lobe. The IC5-aDMN showed increased signal intensity in the SZ group in the ACC. Taken together, these findings indicate impaired signal decreasing in the SZ group compared to the HC group of components belonging to task-negative, or absence, networks during OFF epochs, and a corresponding failure of up-regulating components belonging to task-positive, or presence, networks during ON epochs.
A first interpretation of the findings is of dynamic reallocation of cognitive resources during resting state and task performance, such that certain processes are present both during resting and task periods. In particular this is the case for sustained signal intensity in the ACC (as previously described by McKiernan et al., 2003
; Sridharan et al., 2008
in healthy individuals). We now suggest that the SZ patients may have failed to reallocate cognitive resources from a resting state situation to an active processing situation due to sustained hyper-activation of the default mode network (c.f. Pomarol-Clotet et al., 2008
; Kim et al., 2009a
; Whitfield-Gabrieli et al., 2009
). This could also explain the often reported finding that patients with schizophrenia are impaired compared to HCs on most cognitive functions, including perception, attention, and executive functions (c.f. Saccuzzo et al., 1982
; Berndl et al., 1986
; Green et al., 2000
; Rund et al., 2006
; Harvey, 2010
) seen in standard neuropsychological tests.
An interesting finding is the observation of sustained signal intensity in the ACC in the IC5-aDMN component. ACC is typically activated during periods of active processing or task presence (Bush et al., 2000
for review; Diwadkar et al., 2011
). However the role of the ACC during periods of resting, or task absence, is not clear. Raichle et al. (2001
) did not include the ACC in the default mode network in the 2001 publication, but it is today consensus that the default mode network exists of several networks where ACC is one of the nodes. Current data suggest that the default mode network consists of primary and secondary sub-networks, where the ACC is believed to belong to the primary default mode network (see for example Mannell et al., 2010
). Camchong et al. (2011
) suggested that the ACC is a region comprising of the default mode network, which will also show signal intensity during cognitive processing. Thus, increased ACC signal intensity in the SZ group in the task-negative networks, and decreased signal intensity in the positive networks may reflect hyper- versus hypo-activation of the ACC in schizophrenia during periods of task absence or resting versus periods of active task processing, respectively. Seen as such, the ACC may have a dual role as a cognitive hub during both absence of a stimulus and periods of active processing in the presence of a stimulus or task instruction, and that schizophrenia patients show impairments of ACC activation for both passive and active processing (c.f. Sridharan et al., 2008
; Guerrero-Pedraza et al., 2011
Other components that showed significantly more signal intensity by the SZ group in the task-negative networks were the visual component, IC4-VIS. One of the main nodes in this network, the fusiform gyrus, has been found to be reduced in schizophrenia patients compared to HCs (Takahashi et al., 2006
). Furthermore, increased signal intensity has also been reported in this area by Lagioia et al. (2010
), though in persons with schizotypal personality trait expression. However we do believe that their explanation also can be a possible explaining for our findings, particularly in patients with frequent positive symptoms that could be thought of as engaging a mental imagery component.
Turning to the component showing a significant group difference in the executive component, IC2-EXE, the hypo-frontal signal intensity in the SZ group is similar to what has been frequently reported in the literature of impaired prefrontal function in schizophrenia to cognitive task processing (see for example Fu et al., 2005
). The IC2-EXE component extended into the Insula, SMA, and ACC. As mentioned by Craig (2009
), joint signal intensity of the Insula and the ACC are commonly reported in most studies. The Insula has shown signal intensity with fMRI during affective-, cognitive-, and aversive interceptive processing and therefore claimed for linking emotions to cognitive processes and behavior responses (Paulus and Stein, 2006
), but the Insula has also been suggested to be part of representation of awareness (Craig, 2009
). Further Bush et al. (2000
, review) summarized the ACC to serve as a monitor for crosstalk between brain areas related to conflict and competition. We would like to extend this by suggesting that failure in the ACC signal intensity in the SZ group when required for active processing may be related to the general deficit in cognitive processing seen in schizophrenia. Kim et al. (2009b
) also mentioned in their paper that the ACC, but also the DLPFC, did seem to overlap in their components of relevance. The signal they detected in a component consisting of ACC, DLPFC, thalamus, and Insula, was reported in their paper with higher signal intensity in their controls than their patients (schizophrenia and schizoaffective persons), which also were quite similar to our findings in the IC2-EXE component.
As also discussed by Sridharan et al. (2008
) we believe that the ACC may be of particular interest concerning the dynamic shift between default mode and executive networks, acting like a gate-keeper or switch (c.f.r. Kim et al., 2009b
). The existence of alterations in dynamic networks connectivity has previously been suggested to be one of the reasons for developing more severe symptoms in the schizophrenia patients (Arnsten et al., 2010
). We suggest that an alteration in the ACC alone may contribute to different symptoms depending on which brain structures such alteration further influences (see also van Veen and Carter, 2002
). There seems to be consensus in the literature that the default mode network is up-regulated in the schizophrenia patients compared to HCs, whereas the executive network is down-regulated (however see Fu et al., 2005
for other interpretations).
A limitation of the present results is that when using a brain template, individual changes in brain anatomy among participants may influence location and degree of the brains signal intensity. This would be most prominent for the patient group since brain anatomy changes have commonly been reported in this group (see review by McCarley et al., 1999
; Takahashi et al., 2006
). Moreover it is unclear what effect antipsychotic medication may have on brain structure and function (see, e.g., recent longitudinal studies by Ho et al., 2011
; van Haren et al., 2011
). Lastly, the heterogeneity of symptoms in the SZ group could have influence on the results.