Effect of Schizophrenia on Frontotemporal Activity During Word Encoding and Recognition: A PET Cerebral Blood Flow Study

Ragland, J. Daniel; Gur, Ruben C.; Raz, Jonathan; Schroeder, Lee F.; Kohler, Christian G.; Smith, Robin J.; Alavi, Abass; Gur, Raquel E.

doi:10.1176/appi.ajp.158.7.1114

Cited by 135 publications

(92 citation statements)

References 95 publications

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“…Given the role of the anterior cingulate in monitoring of error commission [Ghering et al, 1993], Carter et al [2001] speculated that increased activity in the anterior cingulate and decreased activity in the DLPFC might occur if patients have impaired attentional control leading to greater response conflict and demands for error monitoring. The increased frontal pole activity found in the current study has also been seen in previous studies of verbal episodic memory [Heckers et al, 1998;Ragland et al, 2001] and attributed to increased retrieval effort in the patient sample. Consistent evidence for reciprocal effects of schizophrenia on prefrontal and temporal-limbic regions indicates the importance of utilizing methods for network analysis of functional imaging data.…”

Section: Discussionsupporting

confidence: 89%

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

Glahn

Ragland

Abramoff

et al. 2005

Human Brain Mapping

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557

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Abstract:Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper-and hypoactivation in schizophrenia. We utilize a quantitative metaanalysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal pole regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper-and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia. Hum Brain Mapp 25:60 -69, 2005.

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Section: Discussionsupporting

confidence: 89%

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

Glahn

Ragland

Abramoff

et al. 2005

Human Brain Mapping

Self Cite

557

393

View full text Add to dashboard Cite

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“…In contrast, schizophrenia patients showed less STG deactivation (relative overactivation) and a positive prefrontal-STG correlation. Further evidence of reciprocal changes in left frontal and left temporal regions was provided by Yurgelen-Todd et al (1996) in an fMRI study of word fluency; by Andreasen et al (1997) in a resting-state PET study; and by Ragland and colleagues in a series of studies of word encoding and recognition (Ragland et al, 2001;.…”

Section: Introductionmentioning

confidence: 90%

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Wolf

Gur

Valdez

et al. 2007

Psychiatry Research: Neuroimaging

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107

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Cognitive deficits, including impaired verbal memory, are prominent in schizophrenia and lead to increased disability. Functional neuroimaging of patients with schizophrenia performing memory tasks has revealed abnormal activation patterns in prefrontal cortex and temporo-limbic regions. Aberrant fronto-temporal interactions thus represent a potential pathophysiological mechanism underlying verbal memory deficits, yet this hypothesis of disturbed connectivity is not tested directly with standard activation studies. We performed within-subject correlations of frontal and temporal timeseries to measure functional connectivity during verbal encoding. Our results confirm earlier findings of aberrant fronto-temporal connectivity in schizophrenia, and extend them by identifying distinct alterations within dorsal and ventral prefrontal cortex. Relative to healthy controls, patients with schizophrenia had reduced connectivity between the dorsolateral prefrontal cortex (DLPFC) and temporal lobe areas including parahippocampus and superior temporal gyrus. In contrast, patients showed increased connectivity between a region of ventrolateral prefrontal cortex (VLPFC) and these same temporal lobe regions. Higher temporal-DLPFC connectivity during encoding was associated with better subsequent recognition accuracy in controls, but not patients. Temporal-VLPFC connectivity was uncorrelated with recognition accuracy in either group. The results suggest that reduced temporal-DLPFC connectivity in schizophrenia could underlie encoding deficits, and increased temporal-VLPFC connectivity may represent an ineffective compensatory effort.

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“…Converging lines of evidence, including postmortem (see for review in Harrison, 1999), in vivo MRI (see for review in Shenton et al, 2001), neuropsychological (Saykin et al, 1991), and functional imaging studies, point to abnormal medial temporal function in schizophrenia. Functional imaging studies have shown abnormalities of these regions during a resting state, (Nordahl et al, 1996;Heckers et al, 1998;Medoff et al, 2001;Tamminga et al, 1992) and abnormal modulation during such tasks as novel picture encoding (Zorrilla et al, 2002), episodic memory encoding (Ragland et al, 2001;Jessen et al, 2003) and retrieval (Heckers et al, 1998;Ragland et al, 2001;Jessen et al, 2003;Weiss et al, 2003).…”

Section: Hippocampal/parahippocampal Regions: Normal Function and Abnmentioning

confidence: 99%

Correlations Between rCBF and Symptoms in Two Independent Cohorts of Drug-Free Patients with Schizophrenia

Lahti

Weiler

Holcomb

et al. 2005

Neuropsychopharmacol

122

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We report on the correlations between whole brain rCBF and the positive and negative symptoms of schizophrenia in two cohorts of patients who were scanned while free of antipsychotic medication. We hypothesized that positive symptoms would correlate with rCBF in limbic and paralimbic regions, and that negative symptoms would correlate with rCBF in frontal and parietal regions. Both cohorts of patients with schizophrenia (Cohort 1: n ¼ 32; Cohort 2: n ¼ 23) were scanned using PET with H 2 15O while free of antipsychotic medication for an average of 21 and 15 days, respectively. Both groups were scanned during a resting state. Using SPM99, we conducted pixel by pixel linear regression analyses between BPRS scores and whole brain rCBF. As hypothesized, positive symptoms correlated with rCBF in the anterior cingulate cortex (ACC) in a positive direction and with the hippocampus/parahippocampus in a negative direction in both patient groups. When the positive symptoms were further divided into disorganization and hallucination/delusion scores, similar positive correlations with ACC and negative correlations with hippocampus rCBF were found. In both cohorts, the disorganization scores correlated positively with rCBF in Broca's area. As expected, negative symptoms correlated inversely with rCBF in frontal and parietal regions. This study provides evidence that limbic dysfunction may underlie the production of positive symptoms. It suggests that abnormal function of Broca's area may add a specific language-related dimension to positive symptoms. This study also provides further support for an independent neurobiological substrate of negative symptoms distinct from positive symptoms. The involvement of both frontal and parietal regions is implicated in the pathophysiology of negative symptoms.

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Effect of Schizophrenia on Frontotemporal Activity During Word Encoding and Recognition: A PET Cerebral Blood Flow Study

Cited by 135 publications

References 95 publications

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Correlations Between rCBF and Symptoms in Two Independent Cohorts of Drug-Free Patients with Schizophrenia

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