Multimodal fusion of structural and functional brain imaging in depression using linked independent component analysis

Previous structural and functional neuroimaging studies have implicated distributed brain regions and networks in depression. However, there are no robust imaging biomarkers that are specific to depression, which may be due to clinical heterogeneity and neurobiological complexity. A dimensional approach and fusion of imaging modalities may yield a more coherent view of the neuronal correlates of depression. We used linked independent component analysis to fuse cortical macrostructure (thickness, area, gray matter density), white matter diffusion properties and resting‐state functional magnetic resonance imaging default mode network amplitude in patients with a history of depression (n = 170) and controls (n = 71). We used univariate and machine learning approaches to assess the relationship between age, sex, case–control status, and symptom loads for depression and anxiety with the resulting brain components. Univariate analyses revealed strong associations between age and sex with mainly global but also regional specific brain components, with varying degrees of multimodal involvement. In contrast, there were no significant associations with case–control status, nor symptom loads for depression and anxiety with the brain components, nor any interaction effects with age and sex. Machine learning revealed low model performance for classifying patients from controls and predicting symptom loads for depression and anxiety, but high age prediction accuracy. Multimodal fusion of brain imaging data alone may not be sufficient for dissecting the clinical and neurobiological heterogeneity of depression. Precise clinical stratification and methods for brain phenotyping at the individual level based on large training samples may be needed to parse the neuroanatomy of depression.     

Multimodal imaging with PET, fMRI and genetic research

Within the last decades, functional magnetic resonance imaging (fMRI) has widely replaced previously used methods such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) in the assessment of functional brain activation. However, PET and SPECT remain important tools for in vivo assessment of neurotransmitter receptors and transporters and for the assessment of baseline regional cerebral blood flow. PET and SPECT also provide a unique opportunity to directly quantify genotype effects on protein expression. We review current nuclear imaging techniques for quantification of genotype effects on neurotransmitter receptors and transporters. Furthermore, we describe first multimodal imaging studies that combined PET, fMRI and genetic data in order to measure effects of genotype or the availability of receptor or transporters on functional brain activation. The clinical relevance of these studies will be illustrated and discussed.     

Multimodal voxel-based meta-analysis of structural and functional magnetic resonance imaging studies in those at elevated genetic risk of developing schizophrenia

Computational brain-imaging studies of individuals at familial high risk for psychosis have provided interesting results, but interpreting these findings can be a challenge due to a number of factors. We searched the literature for studies reporting whole brain voxel-based morphometry (VBM) or functional magnetic resonance imaging (fMRI) findings in people at familial high risk for schizophrenia compared with a control group. A voxel-wise meta-analysis with the effect-size version of Signed Differential Mapping (ES-SDM) identified regional abnormalities of functional brain response. Similarly, an ES-SDM meta-analysis was conducted on VBM studies. A multi-modal imaging meta-analysis was used to highlight brain regions with both structural and functional abnormalities. Nineteen studies met the inclusion criteria, in which a total of 815 familial high-risk individuals were compared to 685 controls. Our fMRI results revealed a number of regions of altered activation. VBM findings demonstrated both increases and decreases in grey matter density of relatives in a variety of brain regions. The multimodal analysis revealed relatives had decreased grey matter with hyper-activation in the left inferior frontal gyrus/amygdala, and decreased grey matter with hypo-activation in the thalamus. We found several regions of altered activation or structure in familial high-risk individuals. Reliable fMRI findings in the right posterior superior temporal gyrus further confirm that alteration in this area is a potential marker of risk.     

Multimodal sensory discrimination deficits in Korsakoff's psychosis

A consistent impairment in odor identification was observed among a group of 21 amnesic patients, diagnosed as having Korsakoff's psychosis. In a subsequent study of eight Korsakoff and matched alcoholic control subjects, a comparable olfactory deficit was again demonstrated, as well as impairment in color discrimination and auditory perception. No such deficit was observed for a picture identification task designed to control for the non-sensory demands of the olfactory test. Step-wise multiple regression analysis showed a significant correlation between odor identification scores and the concentration of the primary metabolite of norepinephrine in lumbar cerebrospinal fluid. The data demonstrate a consistent coincidence between memory impairment and deficient sensory perception among patients with Korsakoff's psychosis.     

Multimodal analysis of functional and structural disconnection in Alzheimer's disease using multiple kernel SVM

Alzheimer's disease (AD) patients exhibit alterations in the functional connectivity between spatially segregated brain regions which may be related to both local gray matter (GM) atrophy as well as a decline in the fiber integrity of the underlying white matter tracts. Machine learning algorithms are able to automatically detect the patterns of the disease in image data, and therefore, constitute a suitable basis for automated image diagnostic systems. The question of which magnetic resonance imaging (MRI) modalities are most useful in a clinical context is as yet unresolved. We examined multimodal MRI data acquired from 28 subjects with clinically probable AD and 25 healthy controls. Specifically, we used fiber tract integrity as measured by diffusion tensor imaging (DTI), GM volume derived from structural MRI, and the graph‐theoretical measures ‘local clustering coefficient’ and ‘shortest path length’ derived from resting‐state functional MRI (rs‐fMRI) to evaluate the utility of the three imaging methods in automated multimodal image diagnostics, to assess their individual performance, and the level of concordance between them. We ran the support vector machine (SVM) algorithm and validated the results using leave‐one‐out cross‐validation. For the single imaging modalities, we obtained an area under the curve (AUC) of 80% for rs‐fMRI, 87% for DTI, and 86% for GM volume. When it came to the multimodal SVM, we obtained an AUC of 82% using all three modalities, and 89% using only DTI measures and GM volume. Combined multimodal imaging data did not significantly improve classification accuracy compared to the best single measures alone. Hum Brain Mapp 36:2118–2131, 2015. © 2015 Wiley Periodicals, Inc.     

New imaging techniques: integrating structural and functional imaging in the head and neck

Traditionally, the mainstay of head and neck MR imaging has been the identification of structural alterations resulting from pathology. Now, the advent of fast MR imaging techniques provides the opportunity for radiologists to integrate structural and functional imaging in the head and neck. This article highlights functional imaging techniques that provide a means toward a complete evaluation of structural integrity and function in various systems of the head and neck.     

Correlative studies of structural and functional imaging in primary progressive aphasia

RATIONALE: To compare and contrast structural and functional imaging in primary progressive aphasia (PPA). METHODS: A cohort of 8 patients diagnosed with PPA presenting with nonfluency were prospectively evaluated. All patients had structural imaging in the form of MRI and in 1 patient CAT scanning on account of a cardiac pacemaker. All patients had single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. RESULTS: SPECT and PET imaging had 100% correlation. Anatomical imaging was abnormal in only 6 of the 8 patients. Wernicke's area showed greater peak Z score reduction and extent of area affected than Broca's area (McNemar paired test: P = .008 for Z score reduction; P = .0003 for extent). PET scanning revealed significant involvement of the anterior cingulum. CONCLUSION: Functional imaging in PPA: (a) identified more patients correctly than anatomic imaging highlighting the importance of SPECT and PET in the diagnosis; and (b) demonstrated the heterogeneous involvement of disordered linguistic networks in PPA suggesting its syndromic nature.     

Memory in functional psychosis.

Acute schizophrenic, chronic schizophrenic, and depressive patients (20 of each) were compared with normal subjects and six groups of patients with organic brain disease. They were given tests of verbal learning (left hemisphere type function) and pattern recognition memory (right hemisphere type function). All functional psychotics showed impaired memory. Acute schizophrenics were, however, only impaired on the verbal task, suggesting left hemisphere dysfunction, while chronic schizophrenics and depressives were impaired on both tasks, suggesting bilateral dysfunction.     

Creatine phosphokinase in functional psychosis

This study was a prospective analysis of CPK levels in patients newly admitted to a psychiatric service in a general hospital. The subjects were classified according to a psychiatric diagnostic taxonomy that has been reliably applied to a large group of patients. Serum CPK was elevated in only 1 of 23 patients with acute psychosis. The results of this study bring into question the value of CPK level as a laboratory aid in the differential diagnosis of mental illness on admission to the hospital.     

Adoption studies in functional psychosis

Summary The scientific rationale of the adoptive methods in genetic studies has been discussed. Three strategies have been employed in psychiatric research. In the adoptee's study method, one examines the adopted away offspring of biological parents, known to be affected by the disorder. A higher prevalence of the disorder among adoptees born to affected biological parents indicates that genetic factors are important. In the adoptee's relatives method, one starts with adoptees known to be disturbed, and then continues by investigating their biological and adoptive families. Comparisons of prevalence rates between relatives of the biological and the rearing index and control families permits one to estimate the influence of the genetic factors. A third method is crossfostering, which is rarely employed. Children of normals who are cross-fostered to adoptive parents who later became ill, are studied. Adoption studies in the field of schizophrenia and manic depressive illness are more specifically discussed. Taken all together, the family, twin and adoption studies support the genetic etiology in schizophrenia and manic depressive illness, although it must be admitted that we need replications to arrive at firm conclusions in the last group of disorder.     

Recent developments in functional and structural imaging of aphasia recovery after stroke

BACKGROUND: Functional and structural neuroimaging techniques can increase our knowledge about the neural processes underlying recovery from post-stroke language impairments (aphasia). AIMS: In the present review we highlight recent developments in neuroimaging research of aphasia recovery. MAIN CONTRIBUTION: We review (a) cross-sectional findings in aphasia with regard to local brain functions and functional connectivity, (b) structural and functional imaging findings using longitudinal (intervention) paradigms, (c) new adjunct treatments that are guided by functional imaging techniques (e.g., electrical brain stimulation) and (d) studies related to the prognosis of language recovery and treatment responsiveness after stroke. CONCLUSIONS: More recent developments in data acquisition and analysis foster better understanding and more realistic modelling of the neural substrates of language recovery after stroke. Moreover, the combination of different neuroimaging protocols can provide converging evidence for neuroplastic brain remodelling during spontaneous and treatment-induced recovery. Researchers are also beginning to use sophisticated imaging analyses to improve accuracy of prognosis, which may eventually improve patient care by allowing for more efficient treatment planning. Brain stimulation techniques offer a new and exciting way to improve the recovery potential after stroke.     

Recent developments in functional and structural imaging of aphasia recovery after stroke

ABSTRACT

Background: Functional and structural neuroimaging techniques can increase our knowledge about the neural processes underlying recovery from post-stroke language impairments (aphasia).

Aims: In the present review we highlight recent developments in neuroimaging research of aphasia recovery.

Main Contribution: We review (a) cross-sectional findings in aphasia with regard to local brain functions and functional connectivity, (b) structural and functional imaging findings using longitudinal (intervention) paradigms, (c) new adjunct treatments that are guided by functional imaging techniques (e.g., electrical brain stimulation) and (d) studies related to the prognosis of language recovery and treatment responsiveness after stroke.

Conclusions: More recent developments in data acquisition and analysis foster better understanding and more realistic modelling of the neural substrates of language recovery after stroke. Moreover, the combination of different neuroimaging protocols can provide converging evidence for neuroplastic brain remodelling during spontaneous and treatment-induced recovery. Researchers are also beginning to use sophisticated imaging analyses to improve accuracy of prognosis, which may eventually improve patient care by allowing for more efficient treatment planning. Brain stimulation techniques offer a new and exciting way to improve the recovery potential after stroke.     

脑功能磁共振成像研究进展

主要综述fMRI产生的历史、成像原理、成像技术和方法、已经取得的成绩以及将来研究发展的方向等。fMRI产生技术广泛应用的20世纪90年代,主要受快速成像技术的影响,从有创走向无创,从而受到神经、认知和心理科学领域的极大关注。fMRI原理是根据神经元兴奋后局部氧耗与血流增幅不一致,而BOLD效应机制成像,间接显示神经元活动。成像主要采用平面回波成像（EPI）和快速小角度激发（FLASH）技术、二者在时间和空间分辨率上各有优劣。最后几年来,fMRI技术对脑功能的研究已取得了巨大的成绩,估计将在这一领域继续拥有非常重要的地位。将来fMRI可能主要在BOLD效应的生理过程、临床应用以及高场磁体的应用等领域进一步展开。