COGNITIVE DEFICIT IN sustained attention has been widely investigated and frequently found in patients with psychiatric disorder but the extent and profile of the deficit may be different.[1, 2] Among schizophrenia patients, sustained attention may be one of the most interesting domains of neurocognitive function because research has consistently found a deficit in sustained attention across subtypes, and this deficit may be a marker of genetic susceptibility for schizophrenia. In addition, sustained attention accounts for considerable variance in social outcomes in schizophrenia patients.
Similarly, research suggests that patients with affective disorders have various deficit profiles in sustained attention depending on their diagnoses and accompanying psychotic features. Patients with bipolar disorder have been reported to have deficits in sustained attention irrespective of accompanying psychotic features, and deficits in attention are seen even among euthymic patients. Unlike the relatively consistent evidence of deficits in sustained attention in patients with bipolar disorder, there have been inconsistent findings in patients with major depressive disorder (MDD). Previous studies have reported that a deficit in sustained attention is a vulnerability marker for MDD even when observed during euthymic or remission states,[7, 8] and a meta-analysis of neurocognitive function in MDD patients found an intermediate effect on tests requiring sustained attention. Other studies, however, have provided contrasting evidence, reporting no deficits in sustained attention in MDD patients.[1, 2] This inconsistency in findings among MDD patients may be due to subtle cognitive deficits or to various clinical states of depression that include psychotic features. Among patients with affective illnesses, patients with non-psychotic depression may have the smallest deficit in sustained attention capacity.
On neuroimaging, schizophrenia patients have been found to have dysfunctional cortical–subcortical–cerebellar circuits,[11, 12] and this cortical–subcortical circuit dysfunction may be associated with deficits in sustained attention.[13-15] Neuroimaging of attention and executive function in MDD patients has also produced equivocal results. Although some neuroimaging studies of depressed patients have reported hypoactivity in the frontal cortex,[16, 17] recent studies have reported prefrontal hyperactivity during working memory and expected emotional judgment. Prefrontal hyperactivity found in the MDD patients may be a sign of cortical inefficiency.
Sustained attention has traditionally been measured using continuous performance tests (CPT) or signal detection paradigms. During a traditional CPT trial, the subject is asked to discriminate and respond to rapidly paced, infrequent targets among frequently presented non-targets. There are several variations in CPT paradigms, which have resulted in variable findings reflecting different aspects of attention and/or executive functions. The sustained attention to response task (SART) is one such variation. The SART is a computerized CPT that is sensitive to slips of action and deficits in sustained attention. In this task, the subject is asked to respond to frequently presented, non-target stimuli, as opposed to responding to infrequent target stimuli. The SART can be a useful tool for clarifying subtle differences in sustained attention capacity between schizophrenia patients and MDD patients.
In this study, we examined cognitive performance and regional cerebral blood flow (rCBF) during the SART in schizophrenia patients, patients with non-psychotic major depression, and healthy control subjects. We sought to further elucidate the cognitive deficits and related neural network dysfunctions seen in schizophrenia and MDD. H215O positron emission tomography (PET) was used to investigate in vivo changes in rCBF during the SART. We hypothesized that the schizophrenia patients and the MDD patients would show differential cognitive performance and associated functional abnormalities in the brain during the SART compared with healthy controls.
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In this study, the schizophrenia group had behavioral performance deficit and different rCBF patterns in the frontal and parietal cortical regions during the modified SART compared to the healthy control group. Meanwhile, there was no significant difference in behavioral performance and rCBF changes during the SART between the MDD and healthy control groups.
Even though vigorous behavioral and neuroimaging studies of attention have been conducted, there is no single brain region that is responsible for attention. Cortico-thalamic-cerebellar circuits have been suggested to be involved in attention and executive function and we found significant rCBF differences during the SART in the frontoparietal regions in the schizophrenia group. Three interrelated but different neuronal networks for attention have been proposed by Fan et al. These three networks exert (i) an alerting function subserved by the thalamic, frontal, and parietal regions; (ii) an orienting function linked by the superior parietal lobe, the temporoparietal junction, and the frontal eye field of the brain; and (iii) an executive control function, which is associated with the anterior cingulate cortex and the lateral prefrontal cortex. The dorsolateral prefrontal cortex plays an important role in the organization of information to facilitate a response, serving as an executive control for sensory information and selection of output.
Based on the present results, abnormalities in activation of the frontoparietal circuits during the SART might be associated with attention dysfunction in schizophrenia. A deficit in sustained attention is a well-replicated finding in schizophrenia patients and it is known to be a valuable diagnostic phenotype of schizophrenia. The prefrontal and parietal cortices play an important role in response inhibition and error-monitoring during the SART.[35, 36] Reduced rCBF during the SART was found in the left cuneus and the left inferior frontal gyrus in the schizophrenia group. Cuneus is known to be involved in attentive visual and spatial information processing and is also included in activated neural network during sustained attention. Reduction of rCBF in the prefrontal regions was consistent with the previous studies, which suggested that prefrontal dysfunction mediated deficit in sustained attention in schizophrenia patients.[12, 39] A frontoparietal network including prefrontal cortex and cuneus may play an important role in sustaining and controlling attention. Increased rCBF, however, was also found in the right frontal and parietal cortices in the present schizophrenia group. More neural resources for response inhibition and error monitoring may be needed in the schizophrenia group, as was reported for an adolescent group in a previous study. Although previous studies reported a correlation with negative symptom severity and SART performance measures, we did not find significant correlation between PANSS symptom severity and behavioral performance during the SART. In the present study, the small number of subjects who underwent neuroimaging may be related to this negative finding.
Among the MDD patients, neither significant behavioral deficit nor rCBF difference during the SART was found compared with the healthy control subjects. Previous studies have reported that there is no deficit in sustained attention among MDD patients.[1, 2] Other studies, however, have reported deficits in sustained attention among depressed patients.[7, 43, 44] In spite of these contrary findings, researchers suggest that psychotic features in patients with affective disorders are a compelling marker for deficits in sustained attention. Both patients with bipolar disorder and MDD patients with psychotic features have shown deficits in sustained attention.[1, 45, 46] In the present study, the MDD group did not have any psychotic features, and the severity of illness ranged from mild to severe. These clinical characteristics of the MDD group may have contributed to behavioral performances and brain activation comparable to those of the healthy control group. We replaced the digit stimuli with facial stimuli in the modified SART to investigate interactions between emotional conditions and sustained attention. We did not, however, find those interactions, but the facial stimuli might provide more perceptual loading than digit stimuli and induce cognitive activation for selective attention to emotional face during the modified SART. Globally increased cognitive activation may contribute to a decrease in the differences between the patient and healthy control groups during the SART in the present study. In the present study, attention-related brain structures including prefrontal cortex and cuneus showed significant difference in rCBF, but there was no significant group difference in rCBF of the facial information processing area including facial fusiform area. A previous study, however, also reported that prefrontal cortex and cuneus might be involved in emotional face perception. We think that the present finding may be associated with dysfunctional network for sustained attention and emotional face perception in schizophrenia.
Several limitations of this study should be noted. First, all of the schizophrenia patients were medicated with one or two antipsychotic drugs, which may have confounded the results. After minimizing the medication effect, the dose of antipsychotic medication was not significantly correlated with rCBF or task performance. All of the MDD patients were medicated with newer antidepressant drugs and no tricyclic antidepressants. We were not concerned with the confounding effects of medication for the MDD group because antidepressant medications are known to have no detrimental impact on cognitive function except tricyclic antidepressants. Also, we assessed depressive symptom severity using only the BDI, which does not reflect objective depressive symptom severity. Another limitation of the present study was that all the patients were outpatients and clinically stable with mild-to-moderate severity. Thus, the present results cannot be generalized to hospitalized patients with severe symptoms.
We combined study of neurocognitive function with functional brain imaging to find evidence of differential changes in brain activity during a sustained attention task among schizophrenia patients and MDD patients. During the SART, we observed a behavioral deficit in attention and perfusion abnormalities in the frontoparietal regions in the schizophrenia patients. Differences in behavioral performance and brain activity during a sustained attention task may be valuable indicators for differentiating schizophrenia from non-psychotic MDD. The prefrontal and parietal network dysfunction associated with sustained attention may be involved in the pathophysiology of schizophrenia.