Regionally Specific Disturbance of Dorsolateral Prefrontal–Hippocampal Functional Connectivity in Schizophrenia

Meyer‐Lindenberg, Andreas; Olsen, Rosanna K.; Kohn, Philip D.; Brown, Timothy T.; Egan, Michael; Weinberger, Daniel R.; Berman, Karen F.

doi:10.1001/archpsyc.62.4.379

Cited by 522 publications

(368 citation statements)

References 55 publications

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“…Consistently, hippocampal disinhibition disrupts hippocampus-dependent rapid place learning performance, as well as aspects of attentional performance that do not normally require the hippocampus, but are mediated by prefrontal-striatal mechanisms. The latter supports that hippocampal dysfunction may partly manifest through deficits in prefrontal-dependent function, consistent with strong hippocampo-prefrontal functional connectivity (Meyer-Lindenberg et al 2005;Bast 2011). The attentional and memory deficits caused by hippocampal neural disinhibition, together with findings that prefrontal-cortical disinhibition disrupts attentional and executive functions (Gruber et al 2010;Enomoto et al 2011;Paine et al 2011;Pehrson et al 2013;Pezze et al 2014;Paine et al 2015;Tse et al 2015), highlight the importance of cortico-hippocampal GABAergic inhibition for cognitive function.…”

Section: Resultssupporting

confidence: 59%

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

et al. 2016

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Section: Resultssupporting

confidence: 59%

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

et al. 2016

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“…Relative to the DLPFC, the possible role of VLPFC abnormalities in schizophrenia has received little attention. We are not aware of any studies reporting increased temporal-VLPFC connectivity, although it occurred at subthreshold levels in one study described above (Meyer-Lindenberg et al, 2005, supplementary online data). While both groups in the current study activated VLPFC equally (Ragland et al, 2005), as in Jennings et al (1998) and Barch et al (2001), other studies have found increased task-related activity of VLPFC in schizophrenia (Kim et al, 2003;Bonner-Jackson et al, 2005;Tan et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The same concern arises with regard to a possible non-specific increase in VLPFC correlations. In order to assess whether the observed group differences in connectivity were indeed selective for temporal-prefrontal circuits, we generated "reverse direction" correlation maps (see also Meyer-Lindenberg et al, 2005), taking as seed ROIs the two prefrontal clusters exhibiting significant group differences, and examining correlations with all voxels in the brain. Connectivity with the DLPFC region was not diffusely increased in controls, but as expected showed greater connectivity primarily in left temporal lobe, with significant (P < 0.05 cluster-corrected) group differences in regions overlapping the STG and the PHIP.…”

Section: Group Differences In Connectivitymentioning

confidence: 99%

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Wolf

Gur

Valdez

et al. 2007

Psychiatry Research: Neuroimaging

106

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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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“…The pathophysiology of schizophrenia involves distributed functional dysconnectivity involving a number of brain regions, 1,2 including the frontal lobe, [3][4][5][6][7][8][9][10] and its language-related areas in the inferior frontal gyrus, 11,12 sensory-motor areas, 13 the temporal lobe, 14 limbic structures, 15,16 and thalamus. [17][18][19][20][21][22][23][24] Despite numerous leads, the reported findings are somewhat inconsistent and the core regions associated with the pathogenesis of schizophrenia still remain controversial.…”

Section: Introductionmentioning

confidence: 99%

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

Wang

Zhang

et al. 2016

SCHBUL

130

129

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Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functionalconnectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functionalconnectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functionalconnectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.

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Regionally Specific Disturbance of Dorsolateral Prefrontal–Hippocampal Functional Connectivity in Schizophrenia

Cited by 522 publications

References 55 publications

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

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