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Four-way multimodal fusion of 7 T imaging data using an mCCA+jICA model in first-episode schizophrenia.

ABSTRACT: Acquisition of multimodal brain imaging data for the same subject has become more common leading to a growing interest in determining the intermodal relationships between imaging modalities to further elucidate the pathophysiology of schizophrenia. Multimodal data have previously been individually analyzed and subsequently integrated; however, these analysis techniques lack the ability to examine true modality inter-relationships. The utilization of a multiset canonical correlation and joint independent component analysis (mCCA + jICA) model for data fusion allows shared or distinct abnormalities between modalities to be examined. In this study, first-episode schizophrenia patients (nSZ =19) and matched controls (nHC =21) completed a resting-state functional magnetic resonance imaging (fMRI) scan at 7 T. Grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), and amplitude of low frequency fluctuation (ALFF) maps were used as features in a mCCA + jICA model. Results of the mCCA + jICA model indicated three joint group-discriminating components (GM-CSF, WM-ALFF, GM-ALFF) and two modality-unique group-discriminating components (GM, WM). The joint component findings are highlighted by GM basal ganglia, somatosensory, parietal lobe, and thalamus abnormalities associated with ventricular CSF volume; WM occipital and frontal lobe abnormalities associated with temporal lobe function; and GM frontal, temporal, parietal, and occipital lobe abnormalities associated with caudate function. These results support and extend major findings throughout the literature using independent single modality analyses. The multimodal fusion of 7 T data in this study provides a more comprehensive illustration of the relationships between underlying neuronal abnormalities associated with schizophrenia than examination of imaging data independently.

SUBMITTER: Lottman KK

PROVIDER: S-EPMC6866979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multimodal fusion is an effective approach to better understand brain diseases. However, most such instances have been limited to pair-wise fusion; because there are often more than two imaging modalities available per subject, there is a need for approaches that can combine multiple datasets optimally. In this paper, we extended our previous two-way fusion model called "multimodal CCA+joint ICA", to three or N-way fusion, that enables robust identification of correspondence among N data types and allows one to investigate the important question of whether certain disease risk factors are shared or distinct across multiple modalities. We compared "mCCA+jICA" with its alternatives in a 3-way fusion simulation and verified its advantages in both decomposition accuracy and modal linkage detection. We also applied it to real functional Magnetic Resonance Imaging (fMRI)-Diffusion Tensor Imaging (DTI) and structural MRI fusion to elucidate the abnormal architecture underlying schizophrenia (n=97) relative to healthy controls (n=116). Both modality-common and modality-unique abnormal regions were identified in schizophrenia. Specifically, the visual cortex in fMRI, the anterior thalamic radiation (ATR) and forceps minor in DTI, and the parietal lobule, cuneus and thalamus in sMRI were linked and discriminated between patients and controls. One fMRI component with regions of activity in motor cortex and superior temporal gyrus individually discriminated schizophrenia from controls. Finally, three components showed significant correlation with duration of illness (DOI), suggesting that lower gray matter volumes in parietal, frontal, and temporal lobes and cerebellum are associated with increased DOI, along with white matter disruption in ATR and cortico-spinal tracts. Findings suggest that the identified fractional anisotropy changes may relate to the corresponding functional/structural changes in the brain that are thought to play a role in the clinical expression of schizophrenia. The proposed "mCCA+jICA" method showed promise for elucidating the joint or coupled neuronal abnormalities underlying mental illnesses and improves our understanding of the disease process.

Project description:Recent data suggest that treatment with antipsychotics is associated with reductions in cortical gray matter in patients with schizophrenia. These findings have led to concerns about the effect of antipsychotic treatment on brain structure and function; however, no studies to date have measured cortical function directly in individuals with schizophrenia and shown antipsychotic-related reductions of gray matter.To examine the effects of antipsychotics on brain structure and function in patients with first-episode schizophrenia, using cortical thickness measurements and administration of the AX version of the Continuous Performance Task (AX-CPT) during event-related functional magnetic resonance imaging.This case-control cross-sectional study was conducted at the Imaging Research Center of the University of California, Davis, from November 2004 through July 2012. Participants were recruited on admission into the Early Diagnosis and Preventive Treatment Clinic, an outpatient clinic specializing in first-episode psychosis. Patients with first-episode schizophrenia who received atypical antipsychotics (medicated patient group) (n?=?23) and those who received no antipsychotics (unmedicated patient group) (n?=?22) and healthy control participants (n?=?37) underwent functional magnetic resonance imaging using a 1.5-T scanner.Behavioral performance was measured by trial accuracy, reaction time, and d'-context score. Voxelwise statistical parametric maps tested differences in functional activity during the AX-CPT, and vertexwise maps of cortical thickness tested differences in cortical thickness across the whole brain.Significant cortical thinning was identified in the medicated patient group relative to the control group in prefrontal (mean reduction [MR], 0.27 mm; P?<?.001), temporal (MR, 0.34 mm; P?=?.02), parietal (MR, 0.21 mm; P?=?.001), and occipital (MR, 0.24 mm; P?=?.001) cortices. The unmedicated patient group showed no significant cortical thickness differences from the control group after clusterwise correction. The medicated patient group showed thinner cortex compared with the unmedicated patient group in the dorsolateral prefrontal cortex (DLPFC) (MR, 0.26 mm; P?=?.001) and temporal cortex (MR, 0.33 mm; P?=?.047). During the AX-CPT, both patient groups showed reduced DLPFC activity compared with the control group (P?=?.02 compared with the medicated group and P?<?.001 compared with the unmedicated group). However, the medicated patient group demonstrated higher DLPFC activation (P?=?.02) and better behavioral performance (P?=?.02) than the unmedicated patient group.These findings highlight the complex relationship between antipsychotic treatment and the structural, functional, and behavioral deficits repeatedly identified in schizophrenia. Although short-term treatment with antipsychotics was associated with prefrontal cortical thinning, treatment was also associated with better cognitive control and increased prefrontal functional activity. This study adds important context to the growing literature on the effects of antipsychotics on the brain and suggests caution in interpreting neuroanatomical changes as being related to a potentially adverse effect on brain function.

Project description:ContextPrevious magnetic resonance imaging (MRI) findings have demonstrated psychopathological symptom-related smaller gray matter volumes in various cingulate gyrus subregions in schizophrenia and bipolar disorder. However, it is unclear whether these gray matter abnormalities show a subregional specificity to either disorder and whether they show postonset progression.ObjectiveTo determine whether there are initial and progressive gray matter volume deficits in cingulate gyrus subregions in patients with first-episode schizophrenia (FESZ) and patients with first-episode affective psychosis (FEAFF, mainly manic) and their specificity to FESZ or FEAFF.DesignA naturalistic cross-sectional study at first hospitalization for psychosis and a longitudinal follow-up approximately 1(1/2) years later.Setting and participantsPatients were from a private psychiatric hospital. Thirty-nine patients with FESZ and 41 with FEAFF at first hospitalization for psychosis and 40 healthy control subjects (HCs) recruited from the community underwent high-spatial-resolution MRI, with follow-up scans in 17 FESZ patients, 18 FEAFF patients, and 18 HCs. Individual subjects were matched for age, sex, parental socioeconomic status, and handedness.Main outcome measuresCingulate gyrus gray matter volumes in 3 anterior subregions (subgenual, affective, and cognitive) and 1 posterior subregion, and whether there was a paracingulate sulcus.ResultsAt first hospitalization, patients with FESZ showed significantly smaller left subgenual (P = .03), left (P = .03) and right (P = .005) affective, right cognitive (P = .04), and right posterior (P = .003) cingulate gyrus gray matter subregions compared with HCs. Moreover, at the 1(1/2)-year follow-up, patients with FESZ showed progressive gray matter volume decreases in the subgenual (P = .002), affective (P < .001), cognitive (P < .001), and posterior (P = .02) cingulate subregions compared with HCs. In contrast, patients with FEAFF showed only initial (left, P < .001; right, P = .002) and progressive subgenual subregion abnormalities (P < .001). Finally, patients with FESZ showed a less asymmetric paracingulate pattern than HCs (P = .02).ConclusionsPatients with FEAFF and FESZ showed differences in initial gray matter volumes and in their progression. Initial and progressive changes in patients with FEAFF were confined to the subgenual cingulate, a region strongly associated with affective disorder, whereas patients with FESZ evinced widespread initial and progressively smaller volumes.

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Four-way multimodal fusion of 7 T imaging data using an mCCA+jICA model in first-episode schizophrenia.

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