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Contribution of structural neuroimaging to the early diagnosis of Alzheimer's disease.

There is compelling evidence for the early involvement of the hippocampal formation in the natural history of Alzheimer's disease (AD). The evidence comes from recent neuropathology, neuropsychology, and neuroimaging studies. AD-type histopathologic changes limited to the hippocampus have been described and may be seen in normal aging subjects. The sites of maximal neuronal loss in the hippocampal formation are in the CA1, subiculum, and entorhinal cortex. Minimally cognitively impaired (MCI) individuals (defined by ratings of functional capacity and psychiatric symptomatology) exhibit a neuropsychological profile that is distinct from that of the unimpaired elderly. Pathologic evidence suggests that most of these cases already have AD brain changes accentuated in the hippocampal region, and our own longitudinal studies reveal that 70% of this group develop dementia within a 4-year period. We have developed a negative-angle axial view designed to cut parallel to the anterior-posterior plane of the hippocampus. Using this modified axial plane of section in conjunction with computed tomography (CT) and magnetic resonance imaging (MRI), we estimated the prevalence of hippocampal atrophy in normal aging and across severity levels of cognitively impaired elderly patients. Longitudinal study shows that hippocampal atrophy is a sensitive and specific predictor of future AD for patients with MCI. MRI volume study of AD patients, controls, and MCI patients shows specific hippocampal volume loss in MCI. We conclude that the atrophic changes associated with early AD can be visualized using qualitative techniques and are readily quantifiable with volumetry. This article is not intended to be comprehensive, but to provide an overview of some of the structural neuroimaging data from our laboratory.

Aged↗

The timing of neurodevelopmental abnormality in schizophrenia: an integrative review of the neuroimaging literature.

In this paper we will review recent neuroimaging research in schizophrenia, with an aim to critically evaluate several recent proposals concerning the nature and the timing of the neuroanatomic abnormalities underlying the disorder. Specifically, enlargement of cerebrospinal fluid spaces, deficits in cortical gray matter, and reduced volume of mesiotemporal structures have all been reported in patients in the first episode of schizophrenia, their first-degree relatives, and individuals with schizotypal personality disorder, supporting the possibility that these abnormalities reflect a genetically mediated neurodevelopmental disorder. These findings from the empirical literature will be synthesized from the perspective of dual cytoarchitectonic trends theory of neurodevelopment, as well as in relation to current conceptions of the schizophrenia prodrome. We believe that the evidence shows that sufficient groundwork has been laid to begin longitudinal neuroimaging studies of adolescents at clinical risk for schizophrenia, in order to more definitively determine the pathophysiology of the disorder. Such information could have significant implications in terms of understanding the prediction, treatment, and ultimately the prevention of schizophrenia.

Journal Article↗

Everyday functioning in relation to cognitive functioning and neuroimaging in community-dwelling Hispanic and non-Hispanic older adults.

The purpose of this study was to examine how a specific informant-based measure of everyday functioning, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE; Jorm & Korten, 1988) relates to cognition and structural neuroimaging in a large multicultural, multilingual sample of Caucasians and Hispanics. Cognitive variables included selected subtests from the Spanish and English Neuropsychological Assessment Scales (SENAS; Mungas et al., 2000): Verbal Memory, Object Naming, Verbal Attention Span, Verbal Conceptual Thinking, and Pattern Recognition. The association between the IQCODE and selected neuroimaging variables, hippocampal volume and white matter hyperintensity, was evaluated in a subsample of English- and Spanish-speaking Hispanic individuals. The cognitive variables showed strong bivariate relationships with the IQCODE, although only Verbal Memory and Object Naming independently predicted level of functional ability. Verbal Memory was the strongest predictor of functional status, accounting for 23% of the variance in the IQCODE. White matter hyperintensity was also independently related to the IQCODE, accounting for 18% of the variance. Hippocampal volume was related to the IQCODE in a simple bivariate analysis, but was not an independent predictor of reported functional status after controlling for age. The relationships between cognitive variables and functional status, as well as between the imaging variables and the IQCODE, did not differ across language-ethnic groups.

Activities of Daily Living↗

A meta-analysis of structural and functional brain imaging in dementia of the Alzheimer's type: a neuroimaging profile.

We conducted a quantitative review of the imaging literature using meta-analytic methodology to characterize further the magnitude of hippocampal deficit in probable Alzheimer's disease (AD) and to determine whether other neuroanatomic structures in AD can better discriminate the disease from normal aging. Additionally, we parceled the discriminability of neuroanatomic structures by duration of disease to determine those structures most sensitive to AD in its early and late stages. One hundred twenty-one studies published between 1984 and 2000 met criteria for inclusion in the present analysis. In total, structural (i.e., CT and MRI) and functional (i.e., SPECT and PET) neuroimaging results from 3511 patients with AD, and 1632 normal healthy controls were recorded across meta-analyses. Our results include neuroimaging profiles for both early onset and longer duration patients with AD. In sum, these profiles yield a signature of diagnostic markers in both cortical and subcortical neuroanatomic areas. This signature is consistent with the clinical phenomenology of Alzheimer's dementia and should aid in the positive identification of AD.

Aged↗

[The value of neuroimaging in diagnosis of epilepsy].

Neuroimaging examines the relationship between abnormalities of brain function in epilepsy patients (seizures, impaired cognitive function, psychiatric co-morbidity etc.) and focal or more widespread brain pathology. Since the mid-1980s, the introduction of magnetic resonance imaging (MRI) into clinical neurology has had an impact on the diagnosis, treatment, and research of epilepsy only comparable with the advent of the electroencephalography (EEG) fifty years ago. MRI plays the important role of identifying single or multiple structural lesions responsible for the epileptic seizures. Thus, visual assessment of MRI plays an important role in the differentiation between symptomatic, cryptogenic, and idiopathic epilepsies. This diagnostic step leads to therapeutic decisions (medical treatment vs. surgery) and prognostic evaluations. If a structural lesion identified with MRI correlates with seizure-type, EEG and other clinical data, the likelihood of rendering the patient seizure free with epilepsy surgery is increased. Clinical research into epilepsy uses quantitative MRI (volumetry, T2-relaxometry, magnetic resonance spectroscopy [MRS], voxel-based morphometry) to reduce those cases initially labeled as cryptogenic. Quantitative MRI questions the belief that there is epilepsy without structural brain abnormality at all. Functional MRI (fMRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT) demonstrate changes associated with epileptic seizures and pathology, and changes associated with EEG abnormalities and their cessation. Functional neuroimaging is also used for the identification of functional brain tissue before surgery. Physiologically or pathologically active neuronal tissue is believed to be identified by glucose or oxygen consumption (PET), cerebral blood flow (PET, SPECT, perfusion MRI), and cerebral blood oxygenation (blood oxygenation level dependent [BOLD] fMRI). PET also offers the opportunity to visualize the in-vivo distribution of neuronal receptors which are implicated in the generation, the spread, and the cessation of seizures.

Brain↗

The role of neuroimaging in the diagnosis of vascular dementia.

Vascular dementia (VaD) and Alzheimer's disease share many pathological and clinical characteristics. Whereas clinical criteria can help differentiate VaD from other types of dementia, neuroimaging is required for confirmation of vascular lesions. Neuroimaging also provides information about location and size of vascular lesions that can lead to a better understanding of symptoms and may help guide therapy.

Aged↗

Meditation states and traits: EEG, ERP, and neuroimaging studies.

Neuroelectric and imaging studies of meditation are reviewed. Electroencephalographic measures indicate an overall slowing subsequent to meditation, with theta and alpha activation related to proficiency of practice. Sensory evoked potential assessment of concentrative meditation yields amplitude and latency changes for some components and practices. Cognitive event-related potential evaluation of meditation implies that practice changes attentional allocation. Neuroimaging studies indicate increased regional cerebral blood flow measures during meditation. Taken together, meditation appears to reflect changes in anterior cingulate cortex and dorsolateral prefrontal areas. Neurophysiological meditative state and trait effects are variable but are beginning to demonstrate consistent outcomes for research and clinical applications. Psychological and clinical effects of meditation are summarized, integrated, and discussed with respect to neuroimaging data.

Brain↗

Sharing neuroimaging studies of human cognition.

After more than a decade of collecting large neuroimaging datasets, neuroscientists are now working to archive these studies in publicly accessible databases. In particular, the fMRI Data Center (fMRIDC), a high-performance computing center managed by computer and brain scientists, seeks to catalogue and openly disseminate the data from published fMRI studies to the community. This repository enables experimental validation and allows researchers to combine and examine patterns of brain activity beyond that of any single study. As with some biological databases, early scientific, technical and sociological concerns hindered initial acceptance of the fMRIDC. However, with the continued growth of this and other neuroscience archives, researchers are recognizing the potential of such resources for identifying new knowledge about cognitive and neural activity. Thus, the field of neuroimaging is following the lead of biology and chemistry, mining its accumulating body of knowledge and moving toward a 'discovery science' of brain function.

Brain↗

The evolution of neuroimaging of spinal cord injury patients over the last decade.

A review is presented concerning the development of new neuroimaging techniques in the last decade which have improved the diagnostic exploration of patients with spinal cord injuries, including studies of possible sequelae. A number of technical developments occurred in the 1980s, which have broadened the diagnostic capabilities of neuroimaging and made its investigative techniques more precise and less invasive. In a summarized way the new or upgraded modalities such as magnetic resonance imaging and angiography, computed tomography and ultrasound, are considered here with regard to the effect that they have had on the clinical management of patients with a traumatized spinal cord.

Diagnostic Imaging↗

Neuroprotection by GDNF-secreting stem cells in a Huntington's disease model: optical neuroimage tracking of brain-grafted cells.

The use of stem cells for reconstructive or neuroprotective strategies can benefit from new advances in neuroimaging techniques to track grafted cells. In the present work, we analyze the potential of a neural stem cell (NSC) line, which stably expresses the glial cell line-derived neurotrophic factor (GDNF) and the firefly luciferase gene (GDNF/Luc-NSC), for cell therapy in a Huntington's disease mouse model. Our results show that detection of light photons is an effective method to quantify the proliferation rate and to characterize the migration pathways of transplanted NSCs. Intravenous administration of luciferine, the luciferase substract, into the grafted animals allowed the detection of implanted cells in real time by an optical neuroimaging methodology, overpassing the limits of serial histological analyses. We observed that transplanted GDNF/Luc-NSCs survive after grafting and expand more when transplanted in quinolinate-lesioned nude mouse striata than when transplanted in non-lesioned mice. We also demonstrate that GDNF/Luc-NSCs prevent the degeneration of striatal neurons in the excitotoxic mouse model of Huntington's disease and reduce the amphetamine-induced rotational behavior in mice bearing unilateral lesions.

Animals↗

Correlation between neuroimaging and neurological outcome in periventricular leukomalacia: diagnostic criteria.

BACKGROUND: Periventricular leukomalacia (PVL) is the most important factor in cerebral palsy in preterm infants. METHODS: In the present study, we investigated 747 preterm infants of less than 36 weeks gestation who were repeatedly examined by cranial ultrasonography and computed tomography (CT) scanning at around 40 weeks of corrected post-menstrual age. The clinical course of these infants was followed for more than 3 years and they were examined by magnetic resonance imaging (MRI) between 12 and 18 months of age. RESULTS: Single examinations in early infancy were not sufficient to diagnose PVL, but the combination of ultrasonography, CT and MRI examinations allowed the clinical diagnosis of PVL. In preterm infants, clinical PVL could be predicted from cystic PVL and periventricular echogenicity (PVE) 3 or PVE 2 prolonged over 3 weeks on ultrasonography and confirmed by MRI after 11 months of corrected age. CONCLUSIONS: We tried to determine diagnostic criteria for PVL by neuroimaging. Such criteria from neuroimaging for PVL may be useful for determining the exact occurrence rate of and clinical risk factors for PVL.

Cerebral Palsy↗

The anatomy of language: contributions from functional neuroimaging.

This article illustrates how functional neuroimaging can be used to test the validity of neurological and cognitive models of language. Three models of language are described: the 19th Century neurological model which describes both the anatomy and cognitive components of auditory and visual word processing, and 2 20th Century cognitive models that are not constrained by anatomy but emphasise 2 different routes to reading that are not present in the neurological model. A series of functional imaging studies are then presented which show that, as predicted by the 19th Century neurologists, auditory and visual word repetition engage the left posterior superior temporal and posterior inferior frontal cortices. More specifically, the roles Wernicke and Broca assigned to these regions lie respectively in the posterior superior temporal sulcus and the anterior insula. In addition, a region in the left posterior inferior temporal cortex is activated for word retrieval, thereby providing a second route to reading, as predicted by the 20th Century cognitive models. This region and its function may have been missed by the 19th Century neurologists because selective damage is rare. The angular gyrus, previously linked to the visual word form system, is shown to be part of a distributed semantic system that can be accessed by objects and faces as well as speech. Other components of the semantic system include several regions in the inferior and middle temporal lobes. From these functional imaging results, a new anatomically constrained model of word processing is proposed which reconciles the anatomical ambitions of the 19th Century neurologists and the cognitive finesse of the 20th Century cognitive models. The review focuses on single word processing and does not attempt to discuss how words are combined to generate sentences or how several languages are learned and interchanged. Progress in unravelling these and other related issues will depend on the integration of behavioural, computational and neurophysiological approaches, including neuroimaging.

Brain↗

When should functional neuroimaging techniques be used in the diagnosis and management of Alzheimer's dementia? A decision analysis.

BACKGROUND: Functional neuroimaging, including positron emission tomography (PET), has been proposed for use in diagnosing Alzheimer's disease-related dementia (AD). OBJECTIVE: The objective of this study was identify the circumstances under which PET scanning for the diagnosis of AD maximizes health outcomes. METHODS: A Markov-model-based decision analysis was conducted using estimates derived from the literature on AD epidemiology, the accuracy of PET, and donepezil treatment efficacy. The target population for the analysis was assumed to be US men and women who either have mild AD or are asymptomatic but at an elevated risk of developing AD owing to disease in a first-degree relative (parent or sibling). The time horizon was the patient lifetime. We compared treatment 1) based on an American Academy of Neurology (AAN) clinical evaluation either alone; 2) in combination with PET scanning; or 3) empirically based on a family history. Outcomes measures were life expectancy, quality-adjusted life-years (QALYs), and (severe) dementia-free life expectancy (SDFLE). RESULTS: For both patient populations, treating all patients based on an AAN evaluation without further testing using PET resulted in the greatest gains in life expectancy, QALYs, and SDFLEs. PET-based testing was the second preferred strategy compared to no intervention. The rankings of the strategies were sensitive to severity of treatment complications: analyses of hypothetical treatments with the potential for severe complications indicated that testing was preferred if the treatment was effective but had moderate complications. CONCLUSIONS: These results suggest that current treatments, which are relatively benign and may slow progression of disease, should be offered to patients who are identified as having AD based solely on an AAN clinical evaluation. A clinical evaluation that includes functional neuroimaging based testing will be warranted, however, when new treatments that are effective at slowing disease progression but have the potential for moderate to severe complications become available.

Aged↗

Neuroimaging findings of cortical dyslamination with cytomegaly.

PURPOSE: Our aims were to identify (a) the characteristic magnetic resonance imaging (MRI) findings of cortical dyslamination with cytomegaly, including dysplastic and destructive lesions; (b) the relationship between MRI findings and pathologic characteristics; (c) the diagnostic role of functional neuroimaging studies in patients with these pathologies. METHODS: The series consisted of 23 adult patients who had proven cortical dyslamination with cytomegaly. The abnormalities found on MRI were subdivided according to the patterns of involvement. They also were compared with the patients' pathologic characteristics. With visual qualitative analysis, [18F]fluorodeoxyglucose with positron emission tomography (FDG-PET), and ictal single-photon emission computed tomography (SPECT), observations were classified as localizing, lateralizing, nonlateralizing, false-localizing, and false-lateralizing. The standard for correct localization of neuroimages was defined to be the resected lobe. RESULTS: Focal abnormalities were found in 14 cases by MRI. Six cases showed typical MRI findings of focal cortical dysplasia, with focal areas of cortical thickening with or without poor grey-white matter differentiation. Focal subcortical high signal intensities on T2-weighted images occurred in two cases. Six patients had the focal destructive pattern. Three of eight cases with normal MRI and four of eight cases with the nondestructive cortical dysplasia pattern had balloon cells. However, these were not found in six patients with the destructive MRI pattern. FDG-PET localized the pathologic lobe in 13 (65%) of 20 cases, and ictal SPECT achieved this in 11 (61.1%) of 18 cases. FDG-PET and ictal SPECT also correctly localized the pathologic lobe in four and two cases with normal MRI, respectively. CONCLUSIONS: Two distinct patterns of abnormal MRI were found in the pathology of cortical dyslamination with cytomegaly. These dysplastic and destructive patterns might reflect different pathogeneses, such as the time of insult. FDG-PET and ictal SPECT have confirmatory and independent diagnostic roles in localizing epileptogenic foci.

Adult↗

Functional neuroimaging of genetic variation in serotonergic neurotransmission.

Serotonin (5-hydroxytryptamine; 5-HT) is a potent modulator of the physiology and behavior involved in generating appropriate responses to environmental cues such as danger or threat. Furthermore, genetic variation in 5-HT subsystem genes can impact upon several dimensions of emotional behavior including neuroticism and psychopathology, but especially anxiety traits. Recently, functional neuroimaging has provided a dramatic illustration of how a promoter polymorphism in the human 5-HT transporter (5-HTT) gene, which has been weakly related to these behaviors, is strongly related to the engagement of neural systems, namely the amygdala, subserving emotional processes. In this commentary, we discuss how functional neuroimaging can be used to characterize the effects of polymorphisms in 5-HT subsystem genes on the response of neural circuits underlying the generation and regulation of mood and temperament as well as susceptibility to affective illness. We argue that in time, such knowledge will allow us to not only transcend phenomenological diagnosis and represent mechanisms of disease, but also identify at-risk individuals and biological pathways for the development of new treatments.

Amygdala↗

Congenital and acquired brain injury. 4. New frontiers: neuroimaging, neuroprotective agents, cognitive-enhancing agents, new technology, and complementary medicine.

UNLABELLED: This self-directed learning module explores the clinical application of new and evolving research frontiers in the field of neuroimaging, neuroprotective agents, and cognition-enhancing medications as applied to patients with brain injury. The current and potential clinical applications of robotic technology, virtual reality, and telemedicine in the field of physical medicine and rehabilitation is explored. The evidence to support a growing interest in and application of complementary medicine techniques in brain injury and other disorders is reviewed. OVERALL ARTICLE OBJECTIVES: (a) To explore the current research and potential clinical applications of medical and technologic advances in neuroprotective agents, cognition-enhancing agents, neuroimaging, virtual reality, robotics, and telemedicine as applicable to brain injury and (b) to identify the evidence to support an expanding use of complementary medicine in brain injury.

Brain Injuries↗

Neonatal ECMO: neuroimaging and neurodevelopmental outcome.

Intracranial injury continues to be a major complication associated with extracorporeal membrane oxygenation (ECMO)-treated neonates. The reported frequency of abnormal neuroimaging has ranged from 28% to 52%, depending on neuroimaging techniques and methods of classification. The purpose of this chapter is to describe types of imaging techniques commonly used to evaluate the ECMO neonate, to specify different types of injuries that have been reported, and to identify factors which increase the risk of injury. We will then describe the functional impact at age 5 years following neonatal brain injury among ECMO infants.

Brain↗

Behavioral Syndrome in Dementia: Neuroimaging Insights.

Noncognitive symptoms contribute prominently to the morbidity of demeting illnesses. CT, MRI, SPECT, and PET are powerful tools used to examine cerbral structure and function and can be utilized to help advance understanding of brain-behavior relationships. Recently, investigators have used neurimaging techniques to study the relationship between structural or functional cerebral deficits and noncognitive symptoms such as depressed mood, delusions, hallucinations, and agitated or disinhibited behaviors that occur in patients with dementia. Although the methodology and subsequent results of studies have varied, three tentative conclusions emerge: (1) Disinhibited and inappropriate social behaviors are most prominent among patients with neuorimaging evidence of frontal cortical dysfunction, across diagnostic categories of dementia syndromes; (2) Depressed mood, apathy, and blunted affect are associated with structural lesions in subcortical nuclei. Frontal cortical dysfunction may be crucial to the development of mood symptoms that result from subcortical lesions; (3) Delusions are associated with dysgunction of paralimbic or heteromodal association areas in the frontal or temporal cortex in patients wtih dementia. The collective neuroimaging evidence suggests that psychiatric and behavioral symptoms in dementia are not random consequences of diffuse brain illness, but are fundamental expressions of regional cerebral pathology. Further development of neuroimaging techniques, more focused neurimaging study designs, and corroboration with neuropathologic studies will help to clarify the pathophysiologic mechanisms involved in neuropsychiatric symptoms and will suggest opportunities for therapeutic intervention.

Journal Article↗