Hypofrontality in unmedicated schizophrenia patients studied with PET during performance of a serial verbal learning task

Hazlett, Erin A.; Buchsbaum, Monte S.; Jeu, Lily Ann; Nenadić, Igor; Fleischman, Michael; Shihabuddin, Lina; Haznedar, M. Mehmet; Harvey, Philip D.

doi:10.1016/s0920-9964(99)00178-4

Cited by 135 publications

(91 citation statements)

References 59 publications

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“…Our results in the ventrolateral IFG region are consistent with most previous neuroimaging studies of verbal learning that compared patients with schizophrenia to healthy individuals (Hazlett et al, 2000;Nohara et al, 2000;Ragland et al, 2001). Given that this region appears to be sensitive to encoding strategy (e.g., deep vs. shallow processing) among healthy individuals (Demb et al, 1995;Otten et al, 2001) and among patients with schizophrenia (Bonner-Jackson et al, 2005;Ragland et al, 2005), it seems likely that our finding of hypoactivation of this region reflects less use of semantic elaboration strategies during learning among the patients in the current study.…”

Section: Discussionsupporting

confidence: 92%

“…The location and direction of temporal lobe abnormalities have been even less consistent. Despite evidence from lesion and imaging studies linking the hippocampus and parahippocampal cortex to new learning among healthy volunteers and a large literature demonstrating abnormalities of hippocampal size in schizophrenia, this area has not consistently been found to be abnormally activated among schizophrenia patients (Hazlett et al, 2000;Nohara et al, 2000;Ragland et al, 2001;Hofer et al, 2003aHofer et al, , 2003b. Those functional imaging studies that did show differences in medial temporal function between patients and comparison participants generally found underactivation of the hippocampus (Eyler Zorrilla et al, 2000;Barch et al, 2002;Jessen et al, 2003;Leube et al, 2003;Achim and Lepage, 2005;Heinze et al, 2006), but overactivation of the parahippocampal gyrus (Ragland et al, 2004) and hippocampus (Ragland et al, 2005) have also been observed.…”

Section: Introductionmentioning

confidence: 96%

“…Previous studies comparing brain response of individuals with schizophrenia to those of healthy participants during the learning stage have shown predominantly frontal and temporal abnormalities (Barch et al, 2002;Eyler Zorrilla et al, 2002b;Jessen et al, 2003;Leube et al, 2003;Ragland et al, 2004;Bonner-Jackson et al, 2005;Ragland et al, 2005;Heinze et al, 2006;Lepage et al, 2006) and a recent meta-analysis confirmed the primary involvement of these regions (Achim and Lepage, 2005). Hypoactivation of the frontal cortex, especially the inferior prefrontal region, was commonly observed (Hazlett et al, 2000;Nohara et al, 2000;Ragland et al, 2001), although one study found overactivation of this region (Bonner-Jackson et al, 2005). The location and direction of temporal lobe abnormalities have been even less consistent.…”

Section: Introductionmentioning

confidence: 97%

“…In hopes of clarifying discrepant findings in the literature, we first conducted a Region-of-Interest (ROI) analysis that focused on the inferior prefrontal cortex and the hippocampus. We chose these two regions because, among healthy individuals, activation in these areas has been most closely associated with subsequent correct recall and recognition of verbal material (as opposed to less consistent relationships with subsequent memory in other encoding-related regions such as the medial frontal gyrus; (Wagner et al, 1999), and they have been shown to be abnormally activated in previous studies of patients with schizophrenia (Eyler Zorrilla et al, 2000;Hazlett et al, 2000;Nohara et al, 2000;Ragland et al, 2001;Barch et al, 2002;Jessen et al, 2003;Leube et al, 2003;Ragland et al, 2004;Achim and Lepage, 2005;Heinze et al, 2006). ROI analyses yield greater power to detect effects because they reduce the number of voxels examined and, thus, the potential for false positive clusters.…”

Section: Introductionmentioning

confidence: 99%

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Brain response abnormalities during verbal learning among patients with schizophrenia

Eyler

Jeste

Brown

2008

Psychiatry Research: Neuroimaging

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Patients with schizophrenia often show verbal learning deficits that have been linked to the pathophysiology of the disorder and result in functional impairment. This study examined the biological basis of these deficits by comparing the brain response of patients with schizophrenia (n=17) to that of healthy comparison participants (n=14) during a verbal paired-associates learning task using functional magnetic resonance imaging (fMRI). Brain response during new word learning was examined within and between groups in two a priori regions of interest, the inferior frontal gyrus and hippocampus, and across the whole brain. In regions of group difference, we also examined the relationship of brain response during learning to later recall of the word pairs. Despite successful matching of levels of word-pair recall, patients' brain response during new learning was abnormal in bilateral regions within the inferior frontal gyrus, a small region in left posterior hippocampus, and other areas within the frontal, parietal and temporal cortex compared to healthy individuals. In some regions, but not in the hippocampus, patients with the most normal brain response also remembered the most word pairs following scanning. Thus, verbal learning deficits found among patients with schizophrenia appear to be related to hypofunction of distributed brain networks.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Brain response abnormalities during verbal learning among patients with schizophrenia

Eyler

Jeste

Brown

2008

Psychiatry Research: Neuroimaging

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“…We assessed rGMR within BAs by tracing coronal slices based on a digitized brain atlas with 33 coronal slice maps of BAs defined by microscopic examination of an entire postmortem brain, a technique detailed elsewhere (Buchsbaum et al, 2001Hazlett et al, 2000;Mitelman et al, 2005). To assess the effect of m-CPP on rGMR, the dependent measure for PET analyses on drug effect was expressed as difference scores (m-CPP-placebo) for rGMR within each BA, calculated by subtracting placebo counts for each region of interest in each subject from the corresponding rGMR from the m-CPP scan.…”

Section: Regions Of Interest Approachmentioning

confidence: 99%

Amygdala–Prefrontal Disconnection in Borderline Personality Disorder

New

Hazlett

Buchsbaum

et al. 2007

Neuropsychopharmacol

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259

160

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Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with 18 fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.

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Magnetic Resonance Imaging of Mediodorsal, Pulvinar, and Centromedian Nuclei of the Thalamus in Patients With Schizophrenia

Kemether¹

2003

Arch Gen Psychiatry

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Background: Postmortem and magnetic resonance imaging (MRI) data have suggested volume reductions in the mediodorsal (MDN) and pulvinar nuclei (PUL) of the thalamus. The centromedian nucleus (CMN), important in attention and arousal, has not been previously studied with MRI.Methods: A sample of 41 patients with schizophrenia (32 men and 9 women) and 60 healthy volunteers (45 men and 15 women) underwent assessment with highresolution 1.2-mm thick anatomical MRI. Images were differentiated to enhance the edges and outline of the whole thalamus, and the MDN, PUL, and CMN were outlined on all slices by a tracer masked to diagnostic status.Results: Significantly smaller volumes of the MDN and PUL were found in patients with schizophrenia compared with controls. Volume relative to brain size was (REPRINTED) ARCH GEN PSYCHIATRY/ VOL 60, WWW.ARCHGENPSYCHIATRY.COM 983

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Hypofrontality in unmedicated schizophrenia patients studied with PET during performance of a serial verbal learning task

Cited by 135 publications

References 59 publications

Brain response abnormalities during verbal learning among patients with schizophrenia

Brain response abnormalities during verbal learning among patients with schizophrenia

Amygdala–Prefrontal Disconnection in Borderline Personality Disorder

Magnetic Resonance Imaging of Mediodorsal, Pulvinar, and Centromedian Nuclei of the Thalamus in Patients With Schizophrenia

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