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Aberrant frontoparietal function during recognition memory in schizophrenia: a multimodal neuroimaging investigation.

ABSTRACT: Prefrontal-parietal networks are essential to many cognitive processes, including the ability to differentiate new from previously presented items. As patients with schizophrenia exhibit structural abnormalities in these areas along with well documented decrements in recognition memory, we hypothesized that these patients would demonstrate memory-related abnormalities in prefrontal and parietal physiology as measured by both functional magnetic resonance imaging and magnetoencephalography (MEG). Medicated outpatients with schizophrenia (n = 18) and age-matched healthy control subjects (n = 18) performed an old-new recognition memory task while physiological data were obtained. Whereas controls exhibited strong, bilateral activation of prefrontal and posterior parietal regions during successful identification of old versus new items, patients exhibited greatly attenuated activation of the right prefrontal and parietal cortices. However, within the patient group, there was strong correlation between memory performance and activation of these right-sided regions as well as a tight correlation between old-new effect-related activations in frontal and parietal regions, a pattern not seen in control subjects. Using MEG, control subjects-but not patients-exhibited a sequential pattern of old > new activity in the left posterior parietal cortex and then right prefrontal cortex; however, patients uniquely exhibited old > new activity in right temporal cortex. Collectively, these findings point to markedly different distributions of regional specialization necessary to complete the old-new item recognition task in patients versus controls. Inefficient utilization of prefrontal-parietal networks, with compensatory activation in temporal regions, may thus contribute to deficient old-new item recognition in schizophrenia.

SUBMITTER: Weiss AP

PROVIDER: S-EPMC2768128 | biostudies-other | 2009 Sep

REPOSITORIES: biostudies-other

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Aberrant frontoparietal function during recognition memory in schizophrenia: a multimodal neuroimaging investigation.

Weiss Anthony P AP Ellis Cameron B CB Roffman Joshua L JL Stufflebeam Steven S Hamalainen Matti S MS Duff Margaret M Goff Donald C DC Schacter Daniel L DL

The Journal of neuroscience : the official journal of the Society for Neuroscience 20090901 36

Prefrontal-parietal networks are essential to many cognitive processes, including the ability to differentiate new from previously presented items. As patients with schizophrenia exhibit structural abnormalities in these areas along with well documented decrements in recognition memory, we hypothesized that these patients would demonstrate memory-related abnormalities in prefrontal and parietal physiology as measured by both functional magnetic resonance imaging and magnetoencephalography (MEG). ...[more]

PMID: 19741141

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Project description:INTRODUCTION:Patients with schizophrenia exhibit several cognitive deficits, including memory impairment. Problems with recognition memory can hinder socially adaptive behavior. Previous investigations have suggested that altered activation of the frontotemporal area plays an important role in recognition memory impairment. However, the cerebral networks related to these deficits are not known. The aim of this study was to elucidate the brain networks required for recognizing socially relevant information in patients with schizophrenia performing an old-new recognition task. METHODS:Sixteen patients with schizophrenia and 16 controls participated in this study. First, the subjects performed the theme-identification task during functional magnetic resonance imaging. In this task, pictures depicting social situations were presented with three words, and the subjects were asked to select the best theme word for each picture. The subjects then performed an old-new recognition task in which they were asked to discriminate whether the presented words were old or new. Task performance and neural responses in the old-new recognition task were compared between the subject groups. An independent component analysis of the functional connectivity was performed. RESULTS:The patients with schizophrenia exhibited decreased discriminability and increased activation of the right superior temporal gyrus compared with the controls during correct responses. Furthermore, aberrant network activities were found in the frontopolar and language comprehension networks in the patients. CONCLUSIONS:The functional connectivity analysis showed aberrant connectivity in the frontopolar and language comprehension networks in the patients with schizophrenia, and these aberrations possibly contribute to their low recognition performance and social dysfunction. These results suggest that the frontopolar and language comprehension networks are potential therapeutic targets in patients with schizophrenia.

Project description:BackgroundThe cognitive deficits of schizophrenia are largely resistant to current treatments and thus are a lifelong illness burden. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition across major cognitive domains; however, the multimodal brain alterations specifically associated with MCCB in schizophrenia have not been examined.MethodsThe interrelationships between MCCB and the abnormalities seen in three types of neuroimaging-derived maps-fractional amplitude of low-frequency fluctuations (fALFF) from resting-state functional magnetic resonance imaging (MRI), gray matter (GM) density from structural MRI, and fractional anisotropy from diffusion MRI-were investigated by using multiset canonical correlation analysis in data from 47 schizophrenia patients treated with antipsychotic medications and 50 age-matched healthy control subjects.ResultsOne multimodal component (canonical variant 8) was identified as both group differentiating and significantly correlated with the MCCB composite. It demonstrated 1) increased cognitive performance associated with higher fALFF (intensity of regional spontaneous brain activity) and higher GM volumes in thalamus, striatum, hippocampus, and the mid-occipital region, with co-occurring fractional anisotropy changes in superior longitudinal fascicules, anterior thalamic radiation, and forceps major; 2) higher fALFF but lower GM volume in dorsolateral prefrontal cortex related to worse cognition in schizophrenia; and 3) distinct domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased fALFF in inferior parietal lobule particularly correlated with decreased social cognition. Medication dose did not relate to these findings in schizophrenia.ConclusionsOur results suggest linked functional and structural deficits in distributed cortico-striato-thalamic circuits may be closely related to MCCB-measured cognitive impairments in schizophrenia.

Project description:Background and hypothesisSchizophrenia is a multidimensional disease. This study proposes a new research framework that combines multimodal meta-analysis and genetic/molecular architecture to solve the consistency in neuroimaging biomarkers of schizophrenia and whether these link to molecular genetics.Study designWe systematically searched Web of Science, PubMed, and BrainMap for the amplitude of low-frequency fluctuations (ALFF) or fractional ALFF, regional homogeneity, regional cerebral blood flow, and voxel-based morphometry analysis studies investigating schizophrenia. The pooled-modality, single-modality, and illness duration-dependent meta-analyses were performed using the activation likelihood estimation algorithm. Subsequently, Spearman correlation and partial least squares regression analyses were conducted to assess the relationship between identified reliable convergent patterns of multimodality and neurotransmitter/transcriptome, using prior molecular imaging and brain-wide gene expression.Study resultsIn total, 203 experiments comprising 10 613 patients and 10 461 healthy controls were included. Multimodal meta-analysis showed that brain regions of significant convergence in schizophrenia were mainly distributed in the frontotemporal cortex, anterior cingulate cortex, insula, thalamus, striatum, and hippocampus. Interestingly, the analyses of illness-duration subgroups identified aberrant functional and structural evolutionary patterns: Lines from the striatum to the cortical core networks to extensive cortical and subcortical regions. Subsequently, we found that these robust multimodal neuroimaging abnormalities were associated with multiple neurobiological abnormalities, such as dopaminergic, glutamatergic, serotonergic, and GABAergic systems.ConclusionsThis work links transcriptome/neurotransmitters with reliable structural and functional signatures of brain abnormalities underlying disease effects in schizophrenia, which provides novel insight into the understanding of schizophrenia pathophysiology and targeted treatments.

Project description:BackgroundLongitudinal neuroimaging studies of major depressive disorder (MDD) have most commonly assessed the effects of antidepressants from the serotonin reuptake inhibitor class and usually reporting a single measure. Multimodal neuroimaging assessments were acquired from MDD patients during an acute depressive episode with serial measures during a 12-week treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine.MethodsParticipants were medication-free MDD patients (n = 32; mean age 40.2 years) in an acute depressive episode and healthy controls matched for age, gender, and IQ (n = 25; mean age 38.8 years). MDD patients received treatment with duloxetine 60 mg daily for 12 weeks with an optional dose increase to 120 mg daily after 8 weeks. All participants had serial imaging at weeks 0, 1, 8, and 12 on a 3 Tesla magnetic resonance imaging (MRI) scanner. Neuroimaging tasks included emotional facial processing, negative attentional bias (emotional Stroop), resting state functional MRI and structural MRI.ResultsA significant group by time interaction was identified in the anterior default mode network in which MDD patients showed increased connectivity with treatment, while there were no significant changes in healthy participants. In the emotional Stroop task, increased posterior cingulate activation in MDD patients normalized following treatment. No significant group by time effects were observed for happy or sad facial processing, including in amygdala responsiveness, or in regional cerebral volumes. Reduced baseline resting state connectivity within the orbitofrontal component of the default mode network was predictive of clinical response. An early increase in hippocampal volume was predictive of clinical response.ConclusionsBaseline resting state functional connectivity was predictive of subsequent clinical response. Complementary effects of treatment were observed from the functional neuroimaging correlates of affective facial expressions, negative attentional bias, and resting state. No significant effects were observed in affective facial processing, while the interaction effect in negative attentional bias and individual group effects in resting state connectivity could be related to the SNRI class of antidepressant medication. The specificity of the observed effects to SNRI pharmacological treatments requires further investigation.Trial registrationRegistered at clinicaltrials.gov ( NCT01051466 ).

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Aberrant frontoparietal function during recognition memory in schizophrenia: a multimodal neuroimaging investigation.

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Aberrant frontoparietal function during recognition memory in schizophrenia: a multimodal neuroimaging investigation.

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