Multimodal Neuroimaging Study of Visual Plasticity in Schizophrenia.
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ABSTRACT:
SUBMITTER: Wijtenburg SA
PROVIDER: S-EPMC8046908 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In this paper we describe an open-access collection of multimodal neuroimaging data in schizophrenia for release to the community. Data were acquired from approximately 100 patients with schizophrenia and 100 age-matched controls during rest as well as several task activation paradigms targeting a hierarchy of cognitive constructs. Neuroimaging data include structural MRI, functional MRI, diffusion MRI, MR spectroscopic imaging, and magnetoencephalography. For three of the hypothesis-driven projects, task activation paradigms were acquired on subsets of ~200 volunteers which examined a range of sensory and cognitive processes (e.g., auditory sensory gating, auditory/visual multisensory integration, visual transverse patterning). Neuropsychological data were also acquired and genetic material via saliva samples were collected from most of the participants and have been typed for both genome-wide polymorphism data as well as genome-wide methylation data. Some results are also presented from the individual studies as well as from our data-driven multimodal analyses (e.g., multimodal examinations of network structure and network dynamics and multitask fMRI data analysis across projects). All data will be released through the Mind Research Network's collaborative informatics and neuroimaging suite (COINS).
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Project description: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.
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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.
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Project description:Previous studies have observed impairments in both brain function and neurometabolite levels in schizophrenia. In this study, we investigated the relationship between brain activity and neurochemistry in off-medication patients with schizophrenia and if this relationship is altered following antipsychotic medication by combining proton magnetic resonance spectroscopy (1H-MRS) with functional magnetic resonance imaging (fMRI). We used single voxel MRS acquired in the bilateral dorsal anterior cingulate cortex (ACC) and fMRI during performance of a Stroop color-naming task in 22 patients with schizophrenia (SZ), initially off-medication and after a 6-week course of risperidone, and 20 matched healthy controls (HC) twice, 6 weeks apart. We observed a significant decrease in ACC glutamate + glutamine (Glx)/Creatine (Cr) levels in medicated SZ patients compared to HC but not compared to their off-medication baseline. In off-medication SZ, the relationship between ACC Glx/Cr levels and the blood oxygen level-dependent (BOLD) response in regions of the salience network (SN) and posterior default mode network (DMN) was opposite than of HC. After 6 weeks, the relationship between Glx and the BOLD response was still opposite between the groups; however for both groups the direction of the relationship changed from baseline to week 6. These results suggest a mechanism whereby alterations in the relationship between cortical glutamate and BOLD response is disrupting the modulation of major neural networks subserving cognitive processes, potentially affecting cognition. While these relationships appear to normalize with treatment in patients, the interpretations of the results are confounded by significant group differences in Glx levels, as well as the variability of the relationship between Glx and BOLD response in HC over time, which may be driven by factors including habituation to task or scanner environment.
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Project description:Visual perceptual learning (VPL) is long-term performance improvement as a result of perceptual experience. It is unclear whether VPL is associated with refinement in representations of the trained feature (feature-based plasticity), improvement in processing of the trained task (task-based plasticity), or both. Here, we provide empirical evidence that VPL of motion detection is associated with both types of plasticity which occur predominantly in different brain areas. Before and after training on a motion detection task, subjects' neural responses to the trained motion stimuli were measured using functional magnetic resonance imaging. In V3A, significant response changes after training were observed specifically to the trained motion stimulus but independently of whether subjects performed the trained task. This suggests that the response changes in V3A represent feature-based plasticity in VPL of motion detection. In V1 and the intraparietal sulcus, significant response changes were found only when subjects performed the trained task on the trained motion stimulus. This suggests that the response changes in these areas reflect task-based plasticity. These results collectively suggest that VPL of motion detection is associated with the 2 types of plasticity, which occur in different areas and therefore have separate mechanisms at least to some degree.
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Project description:BACKGROUND: This research is a one-site neuroimaging component of a two-site genetic study involving patients with schizophrenia at early and later stages of illness. Studies support a role for the neuronal Per-Arnt-Sim 3 (NPAS3) gene in processes that are essential for normal brain development. Specific NPAS3 variants have been observed at an increased frequency in schizophrenia. In humans, NPAS3 protein was detected in the hippocampus from the first trimester of gestation. In addition, NPAS3 protein levels were reduced in the dorsolateral prefrontal cortex of some patients with schizophrenia. Npas3 knockout mice display behavioural, neuroanatomical and structural changes with associated severe reductions in neural precursor cell proliferation in the hippocampal dentate gyrus. This study will evaluate the hypothesis that the severe reductions in neural precursor cell proliferation in the dentate gyrus will be present to some degree in patients carrying schizophrenia-associated NPAS3 variants and less so in other patients. METHODS/DESIGN: Patients enrolled in the larger genetic study (n = 150) will be invited to participate in this neuroimaging arm. The genetic data will be used to ensure a sample size of 45 participants in each genetic subgroup of patients (with and without NPAS3 variants). In addition, we will recruit 60 healthy controls for acquisition of normative data. The following neuroimaging measures will be acquired from the medial temporal region: a) an index of the microcellular environment; b) a macro-structural volumetric measure of the hippocampus; and c) concentration levels of N-acetylaspartate, a marker of neuronal health. DISCUSSION: This study will help to establish the contribution of the NPAS3 gene and its variants to brain tissue abnormalities in schizophrenia. Given the genetic and phenotypic heterogeneity of the disorder and the large variation in outcomes, the identification of biological subgroups may in future support tailoring of treatment approaches in order to optimize recovery.
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