Common and Differential Pathophysiological Features Accompany Comparable Cognitive Impairments in Medication-Free Patients with Schizophrenia and in Healthy Aging Subjects

Abstract

Background Dysfunction of the dorsolateral prefrontal cortex (DLPFC) and parahippocampal region along with poor working memory are common neurophysiological and behavioral features associated with schizophrenia and normal aging. It is, however, unknown whether the associated patterns of neural activation differ between these two groups when their cognitive performance is closely matched in a pairwise manner. The authors sought to pinpoint common and differential pathophysiological features that accompany comparable working memory impairments in schizophrenia and healthy aging. Methods Fifty-three subjects were scanned using H215O PET regional cerebral blood flow measurements during working memory. Seventeen medication-free patients with schizophrenia were individually matched for working memory performance with seventeen healthy aging subjects. Brain activation of the two index groups were compared to each other and to nineteen young healthy individuals. Results Patients with schizophrenia showed right DLPFC hypoactivation, both when compared to age-matched controls, and after direct comparison with working memory performance-matched elderly subjects. Moreover, both groups with working memory deficits shared an inability to suppress parahippocampal and anterior medial prefrontal cortex activation. Conclusions These results provide new insights into the mechanisms by which impaired working memory performance can arise by showing that both common (parahippocampal/anterior medial PFC) and differential (DLPFC) pathophysiological features accompany similar cognitive impairments. The aging data also demonstrate that poor performance is not necessarily accompanied by the DLPFC hypofunction that was seen in schizophrenia. Finally, these results more closely link the DLPFC functional abnormalities in schizophrenia to the pathophysiology of the disorder, rather than to poor performance per se.

Synchronous activation within the default mode network correlates with perceived social support

“…For instance, the DMN-FPCN (fronto-parietal control network) relationship is predictive of intelligence . Moreover, lack of DMN suppression is observed in several mental illness such as schizophrenia (Whitfield-Gabrieli et al, 2009;Anticevic et al, 2011;Metzak et al, 2011;Nejad et al, 2011;Dreher et al, 2012;Fatjó-Vilas et al, 2012) and depression (Sheline et al, 2009;Hamilton et al, 2011). In the present study, however, functional coupling within the TPN regions and the anti-correlation between the DMN and the TPN are not capable of predicting the self-report of perceived social support in spite of the associations between perceived social support and mental disorders.…”

“…As of the role for DMN suppression in a series of mental disorders like schizophrenia (Meyer-Lindenberg et al, 2001;Whitfield-Gabrieli et al, 2009;Anticevic, Repovs, & Barch, 2011;Metzak et al, 2011;Nejad et al, 2011;SalgadoPineda et al, 2011;Schneider et al, 2011;Dreher et al, 2012;Fatjó-Vilas et al, 2012) and depression (Sheline et al, 2009;Hamilton et al, 2011), it is interesting to know whether the anti-correlation between the DMN and the TPN (Task Positive Network) correlates with perceived social support. Composite functional connectivity maps obtained for each ROI in seed-based functional connectivity were used to create the DMN and the TPN masks.…”

Hyperdeactivation of the Default Mode Network in People With Schizophrenia When Focusing Attention in Space

“…40 Furthermore, although DMN hypodeactivation in PSZ is sometimes observed with low-demand tasks in which performance is unimpaired, 33 the phenomenon does tend to be more prominent in more difficult task conditions. 35,38,40,66 The present findings suggest that PSZ are able to suppress DMN activity in response to external task signals Fig. 3.…”

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside

“…Reduced dlPFC activation appears specific to schizophrenia, as individuals with non-schizophrenia psychosis (MacDonald et al 2005), bipolar disorder (Hamilton et al 2009), or depression (Barch et al 2003) do not present with a comparable functional abnormality. Reduced dlPFC activation occurs in treatment-naïve or antipsychotic-treated patients, suggesting it is not a consequence of medication (Dreher et al 2012;Kyriakopoulos et al 2012;Koike et al 2013). Further, the subset of schizophrenia patients who do not exhibit working memory deficits present with increased dlPFC activation compared to controls, implying reduced dlPFC efficiency across patients (Callicott et al 2003).…”