Microstructural and functional MRI studies of cognitive impairment in epilepsy

Cognitive impairment is the most common comorbidity in children with epilepsy, but its pathophysiology and predisposing conditions remain unknown. Clinical epilepsy characteristics are not conclusive in determining cognitive outcome. Because many children with epilepsy do not have macrostructural magnetic resonance imaging (MRI) abnormalities, the underlying substrate for cognitive impairment may be found at the microstructural or functional level. In the last two decades, new MRI techniques have been developed that have the potential to visualize microstructural or functional abnormalities associated with cognitive impairment. These include volumetric MRI, voxel‐based morphometry (VBM), diffusion tensor imaging (DTI), MR spectroscopy (MRS), and functional MRI (fMRI). All of these techniques have shed new light on various aspects associated with, or underlying, cognitive impairment, although their use in epilepsy has been limited and focused mostly on adults. Therefore, in this review, the use of all these different MRI techniques to unravel cognitive impairment in epilepsy is discussed both in adults and children with epilepsy. Volumetric MRI and VBM have revealed significant volume losses in the area of the seizure focus as well as in distant areas. DTI adds evidence of loss of integrity of connections from the seizure focus to distant areas as well as between distant areas. MRS and fMRI have shown impaired function both in the area of the seizure focus as well as in distant structures. For this review we have compiled and compared findings from the various techniques to conclude that cognitive impairment in epilepsy results from a network disorder in which the (micro)structures as well as the functionality can be disturbed.     

Cerebrovascular diseases

Conventional neuroradiological techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), make a fundamental contribution in both the acute and chronic phases of stroke. Recent years have witnessed the development of new imaging modalities, which include diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), CT-angiography (CTA), MR-angiography (MRA), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional MRI (fMRI). While CTA, MRA, DWI and PWI are commonly used for clinical purposes, DTI, MRS and fMRI are becoming increasingly important in the field of experimental research of cerebrovascular diseases, but are still far from becoming of primary usefulness in the everyday clinical setting.     

Diagnostic approaches to predict persistent post-traumatic symptoms after mild traumatic brain injury – a literature review

Mild traumatic brain injury (mTBI) is one of the most frequently diagnosed neurological disorders in emergency departments. Although there are established recommendations for the diagnosis and treatment in the acute stage, there is an on-going debate in which diagnostic methods and risk factors predict unfavourable long-term outcome after mTBI. This literature review addresses the question, which diagnostic approaches may best predict persistent post-traumatic symptoms (pPTS). A literature search for experimental studies from January 2000 to September 2014 evaluating the following diagnostic approaches (1) susceptibility weighted imaging (SWI), (2) diffusion tensor imaging (DTI), (3) magnetic resonance spectroscopy (MRS), (4) functional magnetic resonance imaging (fMRI), as predictive factors of pPTS or unfavourable cognitive outcome in adult populations with mTBI was performed. DTI has been proved to be a valuable tool to identify diffuse axonal injury (DAI) after mTBI. Additionally, some studies showed associations between DAI and unfavourable cognitive outcome. SWI has shown to be a highly sensitive imaging method to identify microbleeds. The presence and quantity of microbleeds in this imaging technique can further provide aetiological evidence for pPTS. MRS provides information about local neurons metabolism and preliminary data show that creatine–phosphocreatine levels measured after mTBI are predictive of cognitive outcome and emotional distress. The results of one study have shown fMRI as a useful tool to differentiate mTBI patients with pPTS from controls and mTBI patients without pPTS in a resting-state condition. From the evaluated diagnostic approaches to predict pPTS after mTBI, DTI, SWI, MRS, and fMRI seem to have adequate sensitivity and specificity as predictive diagnostic tools for pPTS. Large longitudinal clinical trials are warranted to validate the prognostic applicability and practicability in daily clinical practice.     

Effects of social stress on blood leukocyte distribution: the role of alpha- and beta-adrenergic mechanisms

Human immunodeficiency virus (HIV) is associated with central nervous system (CNS) changes that may affect cerebral blood flow (CBF), metabolism, structure, and diffusion. Each of the available neuroimaging techniques offers unique insight into the neural mechanisms underlying HIV, as well as a potential means of monitoring disease progression and treatment response. The purpose of the article is to provide a review of experimental studies evaluating changes related to HIV with imaging techniques, including single-photon emission computed tomography (SPECT), positron emission tomography (PET), volumetric magnetic resonance imaging (MRI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and perfusion MRI (pMRI).     

Multimodal imaging reveals a complex pattern of dysfunction in corticolimbic pathways in major depressive disorder

Major depressive disorder (MDD) is highly prevalent and associated with considerable morbidity, yet its pathophysiology remains only partially understood. While numerous studies have investigated the neurobiological correlates of MDD, most have used only a single neuroimaging modality. In particular, diffusion tensor imaging (DTI) studies have failed to yield uniform results. In this context, examining key tracts and using information from multiple neuroimaging modalities may better characterize potential abnormalities in the MDD brain. This study analyzed data from 30 participants with MDD and 26 healthy participants who underwent DTI, magnetic resonance spectroscopy (MRS), resting‐state functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Tracts connecting the subgenual anterior cingulate cortex (sgACC) and the left and right amygdala, as well as connections to the left and right hippocampus and thalamus, were examined as target areas. Reduced fractional anisotropy (FA) was observed in the studied tracts. Significant differences in the correlation between medial prefrontal glutamate concentrations and FA were also observed between MDD and healthy participants along tracts connecting the sgACC and right amygdala; healthy participants exhibited a strong correlation but MDD participants showed no such relationship. In the same tract, a correlation was observed between FA and subsequent antidepressant response to ketamine infusion in MDD participants. Exploratory models also suggested group differences in the relationship between DTI, fMRI, and MEG measures. This study is the first to combine MRS, DTI, fMRI, and MEG data to obtain multimodal indices of MDD and antidepressant response and may lay the foundation for similar future analyses.     

Toward dysfunctional connectivity: a review of neuroimaging findings in pediatric major depressive disorder

Child and adolescent psychiatric neuroimaging research typically lags behind similar advances in adult disorders. While the pediatric depression imaging literature is less developed, a recent surge in interest has created the need for a synthetic review of this work. Major findings from pediatric volumetric and functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and resting state functional connectivity studies converge to implicate a corticolimbic network of key areas that work together to mediate the task of emotion regulation. Imaging the brain of children and adolescents with unipolar depression began with volumetric studies of isolated brain regions that served to identify key prefrontal, cingulate and limbic nodes of depression-related circuitry elucidated from more recent advances in DTI and functional connectivity imaging. Systematic review of these studies preliminarily suggests developmental differences between findings in youth and adults, including prodromal neurobiological features, along with some continuity across development.     

Other magnetic resonance imaging techniques

Relatively new developments in MRI, such as functional MRI (fMRI), magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) are rapidly developing into imaging modalities that will become clinically available in the near future. They have in common that their signal is somewhat easier to interpret than structural MRI: fMRI mirrors excess cerebral blood flow, in many cases representing brain activity, MRS gives the average volume concentrations of specific chemical compounds, and DTI reflects "directedness" of micro-anatomical structures, of particular use in white matter where fiber bundle disruption can be detected with great sensitivity. While structural changes in MRI have been disappointing in giving a diagnosis of sufficient sensitivity and specificity, these newer methods hold out hope for elucidating pathological changes and differentiating patient groups more rigorously. This paper summarizes promising research results that will yet have to be translated into real life clinical studies in larger groups of patients (e.g. memory clinic patients). Where available, we have tried to summarize results comparing different types of dementia.     

部分多模态MRI在重度抑郁症中的研究进展

重度抑郁症是最常见的高致残性的精神疾病之一,其发病机制尚不清楚。MRI技术作为非侵入性的神经影像技术,可揭示重度抑郁症患者大脑功能状态。与健康对照者相比,重度抑郁症患者额叶、颞叶、海马、扣带回、基底节、小脑等脑区功能改变,可能提示重度抑郁症的病理生理异常。现就多模态MRI,包括弥散张量成像(DTI)、弥散峰度成像(DKI)、磁共振波谱成像(MRS)、功能MRI(fMRI)、神经突方向分散度和密度成像(NODDI)在重度抑郁症中的最新研究成果进行综述,以期对其神经生物学机制有更充分的理解。     

Neuroimaging biomarkers and cognitive function in non-CNS cancer and its treatment: Current status and recommendations for future research

Cognitive changes in patients undergoing treatment for non-central nervous system (CNS) cancers have been recognized for several decades, yet the underlying mechanisms are not well understood. Structural, functional and molecular neuroimaging has the potential to help clarify the neural bases of these cognitive abnormalities. Structural magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), MR spectroscopy (MRS), and positron emission tomography (PET) have all been employed in the study of cognitive effects of cancer treatment, with most studies focusing on breast cancer and changes thought to be induced by chemotherapy. Articles in this special issue of Brain Imaging and Behavior are devoted to neuroimaging studies of cognitive changes in patients with non-CNS cancer and include comprehensive critical reviews and novel research findings. The broad conclusions that can be drawn from past studies and the present body of new research is that there are structural and functional changes associated with cancer and various treatments, particularly systemic cytotoxic chemotherapy, although some cognitive and fMRI studies have identified changes at pre-treatment baseline. Recommendations to accelerate progress include well-powered multicenter neuroimaging studies, a better standardized definition of the cognitive phenotype and extension to other cancers. A systems biology framework incorporating multimodality neuroimaging, genetics and other biomarkers will be highly informative regarding individual differences in risk and protective factors and disease- and treatment-related mechanisms. Studies of interventions targeting cognitive changes are also needed. These next steps are expected to identify novel protective strategies and facilitate a more personalized medicine for cancer patients.     

Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives

Recent studies have indicated the frequent occurrence of neuropsychologic deficits and cognitive complaints after systemic cancer chemotherapy. Most early reports were retrospective, but prospective longitudinal studies are underway. Although the available evidence suggests a fairly diffuse pattern of changes, memory and executive functions could be preferentially affected. Preliminary data also suggest that some individuals might be more vulnerable than others, leading to investigation of genetic and other risk factors. The greatest gap in our knowledge regarding chemotherapy-related cognitive changes is a lack of understanding of the mechanism or mechanisms that account for the observed changes. Several pathophysiological candidates include direct neurotoxic effects leading to atrophy of cerebral gray matter (GM) and/or demyelination of white matter (WM) fibers, secondary immunologic responses causing inflammatory reactions, and microvascular injury. Altered neurotransmitter levels and metabolites could constitute an additional mechanism related to neurotoxic effects. Advanced brain imaging techniques can directly or indirectly assess many of these mechanisms, but to date there has been very limited application of these tools. Morphometric magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) are noninvasive techniques that could yield important complementary data regarding the nature of neural changes after chemotherapy. Electrophysiological studies and targeted molecular imaging with positron emission tomography (PET) could also provide unique information. We review the minimal imaging data available at present and also note studies of other brain disorders or treatment effects that might serve as a model for imaging chemotherapy-induced changes. Large-scale prospective studies are needed to help isolate the pathophysiological mechanisms underlying the cognitive deficits associated with chemotherapy.     

Multimodal imaging in diagnosis of Alzheimer's disease and amnestic mild cognitive impairment: value of magnetic resonance spectroscopy, perfusion, and diffusion tensor imaging of the posterior cingulate region

The purpose of this study was to assess metabolic, perfusion, and microstructural changes within the posterior cingulate area in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using advanced MR techniques such as: spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI). Thirty patients with AD (mean age 71.5 y, MMSE 18), 23 with aMCI (mean age 66 y, MMSE 27.4), and 15 age-matched normal controls (mean age 69 y, MMSE 29.5) underwent conventional MRI followed by MRS, PWI, and DTI on 1.5 Tesla MR unit. Several metabolite ratios (N-acetylaspartate [NAA]/creatine [Cr], choline [Ch]/Cr, myoinositol [mI]/Cr, mI/NAA, mI/Cho) as well as parameters of cerebral blood volume relative to cerebellum and fractional anisotropy were obtained in the posterior cingulate region. The above parameters were correlated with the results of neuropsychological tests. AD patients showed significant abnormalities in all evaluated parameters while subjects with aMCI showed only perfusion and diffusion changes in the posterior cingulate area. Only PWI and DTI measurements revealed significant differences among the three evaluated subject groups. DTI, PWI, and MRS results showed significant correlations with neuropsychological tests. DTI changes correlated with both PWI and MRS abnormalities. Of neuroimaging methods, DTI revealed the highest accuracy in diagnosis of AD and aMCI (0.95, 0.79) followed by PWI (0.87, 0.67) and MRS (0.82, 0.47), respectively. In conclusion, AD is a complex pathology regarding both grey and white matter. DTI seems to be the most useful imaging modality to distinguish between AD, aMCI, and control group, followed by PWI and MRS.     

The role of non-conventional MR techniques to study multiple sclerosis patients

Conventional magnetic resonance imaging (MRI) lacks pathological specificity to the heterogeneous substrates of multiple sclerosis (MS) lesions and is not able to detect subtle, disease-related changes in the normal-appearing white matter (NAWM). As a consequence, the correlation between MRI findings and the long-term evolution of MS is moderate at best. To overcome the limitations of conventional MRI, new quantitative magnetic resonance (MR) techniques, such as cell-specific imaging, magnetization transfer imaging (MTI), proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and functional MR imaging (fMRI) have all been recently applied to the study of MS. These techniques should provide more accurate and pathologically specific estimates of the MS lesion burden than conventional MR and should improve our understanding of the mechanisms leading to MS-related irreversible disability.     

Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment

BackgroundBrain imaging studies of early Alzheimer's disease (AD) have shown decreased metabolism predominantly in the posterior cingulate cortex (PCC), medial temporal lobe, and inferior parietal lobe. This study investigated functional connectivity between these regions, as well as connectivity between these regions and the whole brain.MethodsFunctional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies were performed in subjects with early AD, mild cognitive impairment (MCI), and normal controls.ResultsThe data indicate both decreased fiber connections and disrupted connectivity between the hippocampus and PCC in early AD. The MCI group showed reduced fiber numbers derived from PCC and hippocampus to the whole brain.ConclusionsThe fMRI and DTI results confirmed decreased connectivity from both the PCC and hippocampus to the whole brain in MCI and AD and reduction in connectivity between these two regions, which plausibly represents an early imaging biomarker for AD.     

CPD - education and self-assessment: functional imaging in epilepsy.

Functional imaging plays a growing role in the clinical assessment and research investigation of patients with epilepsy. This article reviews the literature on functional MRI (fMRI) investigation of EEG activity, fMRI evaluation of cognitive and motor functions, magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT) and positron emission tomography (PET) in epilepsy. The place of these techniques in clinical evaluation and their contribution to a better neurobiological understanding of epilepsy are discussed.     

Concussion in athletics: ongoing clinical and brain imaging research controversies

Concussion, the most common form of traumatic brain injury, proves to be increasingly complex and not mild in nature as its synonymous term mild traumatic brain injury (mTBI) would imply. Despite the increasing occurrence and prevalence of mTBI there is no universally accepted definition and conventional brain imaging techniques lack the sensitivity to detect subtle changes it causes. Moreover, clinical management of sports induced mild traumatic brain injury has not changed much over the past decade. Advances in neuroimaging that include electroencephalography (EEG), functional magnetic resonance imaging (fMRI), resting-state functional connectivity, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) offer promise in aiding research into understanding the complexities and nuances of mTBI which may ultimately influence clinical management of the condition. In this paper the authors review the major findings from these advanced neuroimaging methods along with current controversy within this field of research. As mTBI is frequently associated with youth and sports injury this review focuses on sports-related mTBI in the younger population.     

Differences in fMRI and MRS in a monozygotic twin pair discordant for schizophrenia (case report)

OBJECTIVE: This paper presents functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) findings in a monozygotic twin pair discordant for schizophrenia. METHOD: Functional magnetic resonance imaging was used to determine hemispheric lateralization for speech and proton MRS (1H-MRS) was employed to assess the extent of putative insult to anterior hippocampus. RESULTS: Despite concordant right handedness, subject with schizophrenia displayed bilateral activation in areas subserving speech with greater extent of the total activated area compared with the healthy twin. The affected twin displayed relative bilateral decrease in N-acetylaspartate/creatin concentration in the anterior hippocampus compared with the healthy one. CONCLUSION: This is an evidence for non-genetic impairment of cerebral lateralization in monozygotic twin with schizophrenia.     

血管性认知障碍及其功能影像学的研究进展

血管性认知障碍（vascular cognitive impairment,VCI）患病率逐年增加,现已成为老年人群中主要的致残原因,但目前尚缺乏有效的治疗手段。近年来磁共振成像技术迅速发展,尤其是功能影像学,如血氧水平依赖功能磁共振（blood oxygen level dependent functional magnetic resonance i magi ng,BLOD-fMRI）、磁共振波谱技术(magnetic resonance spectroscopy,MRS)、灌注加权成像技术（perfusion weighted imaging,PWI）等,以其高分辨、非创伤性等优点对患者的脑功能进行评价,为血管性认知障碍早期识别、鉴别诊断及评估预后等方面提供了影像学依据。     

Diffusion Tensor and Functional Magnetic Resonance Imaging of Diffuse Axonal Injury and Resulting Language Impairment

Diffuse axonal injury (DAI) is a common aftermath of brain trauma. The diagnosis of DAI is often difficult using conventional magnetic resonance imaging (MRI). We report a diffusion tensor imaging (DTI) study of a patient who sustained DAI presenting with language impairment. Fractional anisotropy (FA) and DTI tractography revealed a reduction of white matter integrity in the left frontal and medial temporal areas. White matter damage identified by DTI was correlated with the patient's language impairment as assessed by functional MRI (fMRI) and a neuropsychological exam. The findings demonstrate the utility of DTI for identifying white matter changes secondary to traumatic brain injury (TBI).     

Lithium therapy for human immunodeficiency virus type 1-associated neurocognitive impairment

The objective of this study was to assess lithium safety and tolerability and to explore its impact on cognition, function, and neuroimaging biomarkers in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. Fifteen cognitively impaired HIV-infected subjects were enrolled in this 10-week open-label study of lithium 300 mg twice daily. Neuroimaging was performed at baseline and following 10 weeks of treatment and included magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and functional MRI (fMRI). Thirteen of the 14 subjects (93%) that complied with the study visits were able to complete the study on lithium and 11 out of 13 (79%) completed the study at the originally assigned dose of 300 mg twice daily. There were no significant changes in CD4⁺ lymphocyte cell count and plasma HIV RNA. Cognitive performance and depressive mood did not improve significantly after the 10-week lithium treatment; however, neuroimaging revealed a decrease in the glutamate+glutamine (Glx) peak in the frontal gray matter, increased fractional anisotropy, and decreased mean diffusivity in several brain areas, and changes in brain activation patterns, suggestive of improvement. These results suggest that lithium can be used safely in HIV-infected individuals with cognitive impairment. Furthermore, the neuroimaging results suggest that lithium may improve HIV-associated central nervous system (CNS) injury; thus, further investigations of lithium as an adjunctive treatment for HIV-associated cognitive impairment are warranted.     

Differential aging of the brain: patterns, cognitive correlates and modifiers

Deciphering the secret of successful aging depends on understanding the patterns and biological underpinnings of cognitive and behavioral changes throughout adulthood. That task is inseparable from comprehending the workings of the brain, the physical substrate of behavior. In this review, we summarize the extant literature on age-related differences and changes in brain structure, including postmortem and noninvasive magnetic resonance imaging (MRI) studies. Among the latter, we survey the evidence from volumetry, diffusion-tensor imaging, and evaluations of white matter hyperintensities (WMH). Further, we review the attempts to elucidate the mechanisms of age-related structural changes by measuring metabolic markers of aging through magnetic resonance spectroscopy (MRS). We discuss the putative links between the pattern of brain aging and the pattern of cognitive decline and stability. We then present examples of activities and conditions (hypertension, hormone deficiency, aerobic fitness) that may influence the course of normal aging in a positive or negative fashion. Lastly, we speculate on several proposed mechanisms of differential brain aging, including neurotransmitter systems, stress and corticosteroids, microvascular changes, calcium homeostasis, and demyelination.