Dysfunction in a prefrontal substrate of sustained attention in schizophrenia

Abnormalities in the Distributed Network of Sustained Attention Predict Neuroleptic Treatment Response in Schizophrenia

“…As expected from our earlier data (Cohen et al 1987(Cohen et al , 1988b, the regional normalized metabolic rates of the prefrontal cortex of this new group of medication-with- drawn patients with schizophrenia (Pickar et al 1992;Cohen et al 1997) were found to be lower than that of the normal controls (NC ϭ 1.051 Ϯ 0.020, SZ ϭ 1.017 Ϯ 0.040, t ϭ 4.33, df ϭ 58, p Ͻ .0001, 2-tailed). A multivariate analysis of the entire frontal cortex by Plane and subsequent univariate analyses of individual regions confirmed differences in Planes B, C, and D of both left and right hemispheres, but not in Planes A (premotor cortex) and E (orbital frontal cortex) (see Table 1).…”

“…The prefrontal cortex metabolic rate of LOW (1.026 Ϯ 0.049) and HIGH (1.008 Ϯ 0.023) patients did not differ. The absence of difference was also observed for the right anterior frontal cortex ROI in Plane C (CRAF: LOW ϭ 1.019 Ϯ 0.046, HIGH ϭ 1.006 Ϯ 0.105), the region to which performance accuracy localizes to in normals (Cohen et al 1987(Cohen et al , 1992. The absence of a prefrontal cortex difference between the two subgroups suggests that the diminished prefrontal cortical metabolic rates of the schizophrenic patients do not simply derive from their poor CPT performance.…”

“…To reduce the likelihood of a Type 1 error in the metabolic rate comparisons of 60 regions in the schizophrenic patients compared to the normal controls, we chose to use multivariate analyses and to examine only regions in which there were a priori reasons for doing so. The prefrontal cortex was examined based on our earlier findings (Cohen et al 1987) that the metabolic rates of prefrontal cortex regions of interest, but not regions of interest in the pre-motor or orbital frontal cortex were reduced in the schizophrenic patients. When the prefrontal cortex is referred to in the text in the comparison between groups, it is the mean of the left and right anterior and posterior ROIs of the frontal cortex in Planes B, C, and D. The basal ganglia was also examined for differences because of the reports of both abnormally high and abnormally low metabolic rates in schizophrenia (Buchsbaum et al 1992a;Early et al 1987;Resnick et al 1988;Wolkin et al 1985).…”

“…Sustained attention on continuous performance tasks (CPT) has served as a laboratory model of this failure in positron emission tomography (PET) studies of regional glucose metabolic rates (Cohen et al 1988a). In PET studies (Buchsbaum et al 1990(Buchsbaum et al , 1992aCohen et al 1987), medication-withdrawn and neuroleptic-naive patients with schizophrenia performing CPT, and in our study, regardless of performance and medication status, were found to have abnormally low functional activity of the midprefrontal cortex area that served as the biological determinant of this task in normal controls (Cohen et al 1987(Cohen et al , 1988c(Cohen et al , 1992. These studies, although consistent with earlier data from a variety of methods on the importance of the right prefrontal cortex in attentional processes (Mesulam 1981), and subsequent and concurrent other PET studies utilizing cerebral blood flow as a measure of activation (Posner and Petersen 1990), were all performed at low resolutions and most, if not all, with calculated attenuation corrections.…”

Clinical and Sensorimotor Gating Effects of Ketamine in Normals

“…Schizophrenia, and negative symptoms of schizophrenia in particular, have been associated with decreased frontal metabolic activity (Buchsbaum et al 1982;Buchsbaum et al 1990;Farkas et al 1984;Wolkin et al 1985;Cohen et al 1987;Volkow et al 1987;Wolkin et al 1992;Siegel et al 1993). However, this is not a consistent finding.…”