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Diagnostic yield for neuroimaging in patients with unilateral eye or facial pain.

BACKGROUND: The neuroimaging evaluation of isolated pain in or around the eye has not been studied previously. We report the low diagnostic yield of neuroimaging in patients who have a normal ocular examination and unilateral eye pain or facial pain predominantly affecting the eye. METHODS: Retrospective review of patients referred to 3 neuro-ophthalmology practices for unexplained pain in or around the eye. Inclusion criteria were adults with isolated unilateral eye/facial pain, neuroimaging, and a normal eye exam. Ex-clusion criteria were symptoms typical of a defined pain syndrome (e.g., trigeminal neuralgia or giant cell arteritis), and exam findings that would account for the pain. RESULTS: One hundred and twenty-seven (127) of the 760 reviewed patients met study criteria, and underwent MRI (75) or CT (34) scans, or both (18). Imaging was normal in 106 (83%). Abnormalities (n = 21) on imaging (17%) included nonspecific T2-weighted hyperintensities (10), sinusitis (5), superior ophthalmic vein enlargement (1), pontine lacunar infarct (1), Chiari malformation (1), thalamic mass (1), old occipital stroke (1), and focal enlargement of the third cranial nerve (1). INTERPRETATION: Although imaging showed abnormalities in 17% of cases of isolated pain in or around the eye, only 2 abnormalities were believed to be possibly related to the pain and only 1 case was probably related. The diagnostic yield of neuroimaging in patients with a normal examination and isolated, unilateral eye/facial pain referred to a neuro-ophthalmologist is low.

Adult↗

Functional neuroimaging in Alzheimer's type dementia.

This article aims to review the role of the functional neuroimaging modality of positron emission tomography (PET) in the early diagnosis of Alzheimer's disease (AD). Clinical diagnosis in the early disease stages is difficult and treatments are emerging which rather than reversing structural damage are likely to slow or halt the disease process. While currently no routine diagnostic test confirms AD presence, imaging techniques are an important expanding field in biological neuropsychiatry. The challenge for neuroimaging methods is to achieve high specificity and sensitivity in early disease stages. Glucose metabolic PET imaging with fluorodeoxyglucose (FDG) has the potential to detect very early neocortical dysfunction before even abnormal neuropsychological testing is obtainable. The implications are for the identification of minimally symptomatic patients that could benefit most from treatment strategies, as well as the monitoring of treatment response and possible therapeutic deceleration of the disease. FDG PET correlates with AD neuropathology and is able to indicate disease progression or severity, meeting both functional neuroimaging prerequisites in diagnosing AD. A combination of functional neuroimaging with different techniques should be able to provide highest diagnostic specificity in diagnosing dementia. This may even lead to a new classification of dementias according to differences in the causative aetiology.

Aged↗

Neuroimaging studies of semantic memory: inferring "how" from "where".

For nearly two decades, functional neuroimaging studies have attempted to shed light on questions about the representation, organization, and retrieval of semantic knowledge. This review examines some of the major findings in this area. For example, functional neuroimaging studies have examined the extent to which there is a unitary semantic system or a series of multiple semantic subsystems organized by input modality, knowledge attribute, and/or taxonomic category. Additionally, functional neuroimaging studies have investigated the contributions of frontal cortex to semantic retrieval and selection. Collectively, these studies demonstrate that functional neuroimaging can offer more than neuroanatomical localization information; in addition, these studies offer new insights into longstanding questions about semantic memory.

Brain↗

Evidence of optic pathway gliomas after previously negative neuroimaging.

PURPOSE: The authors emphasize the potential for the development of anterior visual pathway gliomas, evidenced by computed tomography (CT) or magnetic resonance imaging (MRI) scans, in neurofibromatosis type 1 (NF1) patients who previously had normal neuroimaging studies. METHODS: The clinic charts and CT and MRI scans were retrospectively reviewed for all patients evaluated at the neurofibromatosis clinic of one referral center over a period of 7 years. Patients with neuroimaging studies demonstrating anterior visual pathway gliomas who previously had normal scans were identified, and their cases are described in detail. A similar, previously reported series, from the pediatric literature, was also reviewed. RESULTS: Eight percent (28/360) of patients had CT or MRI scans revealing optic gliomas. Two of these patients had normal neuroimaging studies previously. CONCLUSION: A negative neuroimaging study in an NF1 patient does not exclude the future development of an optic glioma.

Antineoplastic Combined Chemotherapy Protocols↗

An apparatus and behavioral training protocol to conduct positron emission tomography (PET) neuroimaging in conscious rhesus monkeys.

Nonhuman primates offer a unique resource in neuroimaging research, providing the opportunity to manipulate appropriate biological and behavioral variables under well-controlled experimental conditions in an animal model that is closely related to humans, both functionally and neuroanatomically. The present report describes the development and standardization of PET neuroimaging protocols in conscious rhesus monkeys and their application to characterize the acute effects of cocaine on cerebral blood flow. Specific attention was devoted to the development of an effective and comfortable head restraint device to be used in the imaging of conscious monkeys. The restraint device was designed to attach to a standard primate chair to facilitate frequent immobilization. Subjects received extensive behavioral training prior to neuroimaging in order to ensure their comfort and minimize potential stress associated with the imaging protocols. Functional changes in cerebral blood flow were characterized in three subjects with the positron-emitting tracer 15O water following acute i.v. administration of cocaine. Regions of interest were defined on MRI scans with a high degree of accuracy. Cocaine caused pronounced increases in cerebral blood flow at 5 min postinjection that diminished markedly within 25 min. The results document the feasibility to conduct PET neuroimaging studies of cerebral blood flow in conscious nonhuman primates. Extension of the methodology to include brain activation during behavioral studies could contribute significantly to the growing discipline of behavioral neuroscience.

Animals↗

Ethics of neuroimaging in pediatric development.

Neuroimaging in pediatrics is accompanied by all the ethical dilemmas associated with neuroimaging in adults, magnified significantly. The defining characteristics of childhood make working ethically with the population particularly problematic. Children have not developed the rational capabilities necessary to make informed decisions and the variability and change associated with development contribute to heightened risks and/or benefits of any procedure and limit interpretation of data. As a consequence, fewer pediatric than adult neuroimaging research studies have been done, further limiting general knowledge of the field. Significant strides have been made just within the past few years with the collection of normative data sets of healthy children. Recommendations on how to proceed with pediatric neuroimaging studies while ensuring ethical treatment of the participants are presented.

Bioethics↗

Ethical considerations in neuroimaging and its impact on decision-making for neonates.

Neuroimaging can now provide information about structure and function. Despite new and improved neuroimaging technologies applicable to the newborn, predictions about later cognition, learning, social and emotional behavior, and neuromuscular capabilities, based on images of a fetus inside or a newborn outside the womb, are fraught with difficulties that go beyond technical ones. The interpretation of neuroimages may be necessary but it is not sufficient for decision-making related to the withholding or withdrawing of medical support for neonates. As the explanatory reach of neuroimaging increases, there will still need to be consideration of ethical issues as they relate to the best interests of the neonate and the neonate's parents, the quality of life of the neonate and non-beneficial treatment. Once this is appreciated, the boundary between the technical and the ethical will be less often disputed.

Brain↗

Neuroimaging abnormalities in children with an apparent first unprovoked seizure.

OBJECTIVE: To determine the incidence and type of neuroimaging abnormalities in children presenting with a first seizure. METHODS: In a prospective observational study, 411 children with a first afebrile seizure were seen between 1983 and 1992. Imaging studies were performed in 218 (53%). For this analysis we examined the most sensitive neuroimaging study performed which included 159 computed tomography scans and 59 magnetic resonance imagings (MRI). RESULTS: Four children were found to have lesions requiring intervention (brain tumor in two, neurocysticercosis in two). The remaining 407 were enrolled in a follow-up study of children with a first unprovoked seizure. After a mean follow-up of >10 years, none have developed clinical evidence of a tumor. In these 411 children, 45 (21%) of 218 imaging studies were abnormal. The most common abnormalities were focal encephalomalacia (n=16) and cerebral dysgenesis (n=11). Although children with partial seizures were more likely to be imaged (64%) than children with generalized seizures (43%) (P<0.001), the fraction of abnormal imaging studies was similar in both groups. Six children with a normal neurological examination who were initially classified as cryptogenic were subsequently found to have errors of cerebral migration on MRI. The incidence of lesions requiring acute intervention in children presenting with a first seizure is low. A significant proportion will have neuroimaging abnormalities particularly on MRI. CONCLUSIONS: Neuroimaging should be considered in any child with a first seizure who does not have an idiopathic form of epilepsy.

Adolescent↗

Neuroimaging and the functional neuroanatomy of psychotherapy.

BACKGROUND: Studies measuring the effects of psychotherapy on brain function are under-represented relative to analogous studies of medications, possibly reflecting historical biases. However, psychological constructs relevant to several modalities of psychotherapy have demonstrable neurobiological correlates, as indicated by functional neuroimaging studies in healthy subjects. This review examines initial attempts to measure directly the effects of psychotherapy on brain function in patients with depression or anxiety disorders. METHOD: Fourteen published, peer-reviewed functional neuroimaging investigations of psychotherapy were identified through a MEDLINE search and critically reviewed. Studies were compared for consistency of findings both within specific diagnostic categories, and between specific modalities of psychotherapy. Results were also compared to predicted neural models of psychotherapeutic interventions. RESULTS: Behavioral therapy for anxiety disorders was consistently associated with attenuation of brain-imaging abnormalities in regions linked to the pathophysiology of anxiety, and with activation in regions related to positive reappraisal of anxiogenic stimuli. In studies of major depressive disorder, cognitive behavioral therapy and interpersonal therapy were associated with markedly similar changes in cortical-subcortical circuitry, but in unexpected directions. For any given psychiatric disorder, there was only partial overlap between the brain-imaging changes associated with pharmacotherapy and those associated with psychotherapy. CONCLUSIONS: Despite methodological limitations, initial neuroimaging studies have revealed convergent and mechanistically sensible effects of psychotherapy on brain function across a range of psychiatric disorders. Further research in this area may take advantage of emerging neuroimaging techniques to explore a broader range of psychotherapies, with the ultimate goal of improving clinical decision-making and treatment.

Anxiety Disorders↗

Can neuroimaging techniques identify individuals at risk of developing Alzheimer's disease?

Recent studies indicate that neuroimaging techniques such as magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography can accurately differentiate patients with Alzheimer's disease (AD) from elderly controls. This report reviews the results of neuroimaging studies of two at-risk populations: subjects with the epsilon 4 allele of the apolipoprotein E and those with mild cognitive impairment. The results of the work published to date indicate that the presence of the epsilon 4 allele is a risk factor for AD and that its predictive validity can be enhanced by neuropsychological and/or neuroimaging evaluation. The results also show that patients with mild cognitive impairment display a number of structural and functional imaging abnormalities that are more pronounced in the temporal and parietal lobes. We suggest that the use of neuroimaging techniques can improve the detection of subjects early in the course of AD, although the sensitivity and the specificity of this approach still await a more detailed prospective evaluation.

Alzheimer Disease↗

Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease.

Alzheimer's disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular.

Alzheimer Disease↗

Neuroimaging in bipolar disorder.

OBJECTIVE: The authors reviewed neuroimaging studies of bipolar disorder in order to evaluate how this literature contributes to the current understanding of the neurophysiology of the illness. METHOD: Papers were reviewed as identified, using the NIMH PubMed literature search systems that reported results of neuroimaging studies involving a minimum of five bipolar disorder patients compared with healthy comparison subjects. RESULTS: Structural neuroimaging studies report mixed results for lateral and third ventriculomegaly. Recent studies suggest subcortical structural abnormalities in the striatum and amygdala, as well as the prefrontal cortex. Proton spectroscopic studies suggest that abnormalities in choline metabolism exist in bipolar disorder, particularly in the basal ganglia. Additionally, phosphorous MRS suggests that there may be abnormalities in frontal phospholipid metabolism in bipolar disorder. Functional studies have identified affective state-related changes in cerebral glucose metabolism and blood flow, particularly in the prefrontal cortex during depression, but no clear abnormalities specific to bipolar disorder have been consistently observed. CONCLUSIONS: The current literature examining the neurophysiology of bipolar disorder using neuroimaging is limited. Nonetheless, abnormalities in specific frontal-subcortical brain circuits seem likely. Additional targeted studies are needed to capitalize on this burgeoning technology to advance our understanding of the neurophysiology of bipolar disorder.

Basal Ganglia↗

Seizure semiology and neuroimaging findings in patients with midline spikes.

PURPOSE: Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes. METHODS: We reviewed the EEG database of the University of Michigan Medical Center and identified 35 patients with midline spikes. Information about seizure types and neuroimaging results was obtained from a review of medical records. The seizures were classified according to the International League Against Epilepsy (ILAE) criteria and semiologic classification. RESULTS: Twenty-nine (83%) patients had a history of seizures. Complex partial seizures and simple partial seizures were the most common seizure types, experienced by 66% of patients. The age at seizure onset was within the first 10 years in 90% of patients. According to the semiologic seizure classification, automotor seizures and tonic seizures were the most common seizure types. Neuroimaging studies were abnormal in 45% of patients. When focal abnormalities were detected, they were lateralized to one of the frontal lobes in all cases. CONCLUSIONS: Our results indicate that in the majority of patients, midline spikes represent focal epileptiform activity rather than fragments of generalized discharges, and are most commonly associated with seizures of partial onset. Automotor seizures and tonic seizures are the most common semiologies. Focal radiologic abnormalities tend to be lateralized to one of the frontal lobes.

Adolescent↗

Abnormal neuroimaging in patients with benign epilepsy with centrotemporal spikes.

PURPOSE: Neuroimaging procedures are usually unnecessary in benign epilepsy of childhood with centrotemporal spikes (BECTS) but are often performed before a specific diagnosis has been reached. By definition, BECTS occurs in normal children; however, recent reports have shown that it also can affect children with static brain lesions. We evaluated the prevalence of abnormal neuroimaging in BECTS and assessed whether the lesions had influenced the clinical and EEG expression of this epilepsy. RESULTS: Among 98 consecutive cases first referred between 1984 and 1999, neuroimaging had been performed in 71 (72%) [magnetic resonance imaging (MRI), 20; computed tomography (CT), 59; MRI+CT, eight]. In ten (14.8%), neuroradiologic procedures were abnormal: enlargement of lateral venticles in five cases including a shunted hydrocephalus in two (no etiology in one, neonatal intraventricular hemorrhage in one), a moderate ventricular dilation in one (neonatal distress), a slight ventricular dilation and hypersignal intensities in the white matter in one (premature birth at 27 weeks), and a moderate enlargement of the right temporal horn in one. A right hippocampal atrophy, a biopercular polymicrogyria, a cavum septum pellucidum, a small cystic lesion located in the epiphysis, and an agenesis of the corpus callosum with macrocrania also were observed once each. The outcome was benign in all, in accordance with the overall prognosis of BECTS. CONCLUSIONS: This study confirms that neuroimaging may be abnormal in patients with BECTS and shows that the presence of brain lesions has no influence on the prognosis. Conversely, BECTS can be diagnosed in patients with brain lesions with or without significant neurologic history or abnormalities.

Adolescent↗

Bridging the gap between neuroimaging and neuropsychology: using working memory as a case-study.

Neuropsychology and neuroimaging both provide information about the relationship between brain structure and function, and thus attempt to understand if the neural basis of cognition should benefit from converging results obtained across the two methods. However, serious attempts to integrate the two methodologies face several challenges, such as differences in basic paradigm designs. To illustrate these points, this article will review neuropsychological and neuroimaging research in the area of working memory. Points of discussion will include discrepancies between neuropsychological and neuroimaging evidence for domain-specific rehearsal systems, the role of left inferior parietal cortex in phonological storage, and the contributions of Brocas area and the cerebellum to articulatory rehearsal. Methodological factors and assumptions that may account for these discrepancies, and the steps that could be taken to overcome them, will be evaluated. The overall objective of this "case study" is to encourage neuroimagers and neuropsychologists to evaluate seriously the results obtained in both methodologies when formulating interpretations of their data and when designing new studies.

Brain↗

Investigating cognitive neuroplasticity in single cases: lessons learned from applying functional neuroimaging techniques to the traditional neuropsychological case study framework.

We summarize two case studies as a context for discussing the use of neuroimaging as a convergent methodology in the study of neuroplasticity in single subjects. Throughout this paper we argue for a different approach for including neuroimaging in these types of study. Previous case studies of neuroplasticity in patients (ours as well as others reported elsewhere) have added neuroimaging to the traditional neuropsychological framework of comparing patient results with matched control groups, and synthesized results through descriptions of anatomical and behavioral dissociations. This type of approach is referred to as the comparison approach. We advocate a different approach that builds on findings from previous behavioral skill learning research. Specifically, we propose adding neuroimaging throughout learning or recovery of the ability of interest and making inferences from systematic changes in activation topography and intensity that occur within the context of predicted behavioral changes. We dub this approach the online approach. This approach should allow future investigators to circumvent many of the interpretation pitfalls that are common in comparison studies.

Adult↗

Auditory hallucinations: Insights and questions from neuroimaging.

INTRODUCTION: The human brain has the capacity to hallucinate but rarely, except in severe neuropsychiatric conditions such as schizophrenia, do they naturally predominate. The neural basis of auditory verbal hallucinations (AVHs) has been investigated using structural and functional neuroimaging techniques. So far, no studies have defined a model that explains why auditory hallucinations are perceived in the absence of an external stimulus. METHODS: A selective literature review was undertaken specifically to focus on: (1) clinical phenomenology; (2) putative brain systems involved in the pathogenesis of auditory hallucinations as suggested by neuroimaging studies; (3) contributions and weaknesses of the neuroimaging findings in potentially bridging the gap between the neuroscience and phenomenology. Throughout, an attempt was made to ask questions as much as to answer them. RESULTS: Functional domains implicated in the genesis of auditory verbal hallucinations include: (1) hearing and language; (2) "sense of reality", including externality of voices; (3) attention and salience; (4) emotional response; (5) memory; (6) volition and self-monitoring; (7) impulse control. Each of these domains can be mapped onto neural "systems" that comprise components that overlap with brain regions known to activate during the experience of auditory hallucinations. CONCLUSIONS: In the next phase of neuroimaging research into the pathogenesis of auditory hallucinations we need to examine component processes that lead to the patient's perception of them as real.

Journal Article↗

In vivo characterization of traumatic brain injury neuropathology with structural and functional neuroimaging.

Quantitative neuroimaging is increasingly used to study the effects of traumatic brain injury (TBI) on brain structure and function. This paper reviews quantitative structural and functional neuroimaging studies of patients with TBI, with an emphasis on the effects of diffuse axonal injury (DAI), the primary neuropathology in TBI. Quantitative structural neuroimaging has evolved from simple planometric measurements through targeted region-of-interest analyses to whole-brain analysis of quantified tissue compartments. Recent studies converge to indicate widespread volume loss of both gray and white matter in patients with moderate-to-severe TBI. These changes can be documented even when patients with focal lesions are excluded. Broadly speaking, performance on standard neuropsychological tests of speeded information processing are related to these changes, but demonstration of specific brain-behavior relationships requires more refined experimental behavioral measures. The functional consequences of these structural changes can be imaged with activation functional neuroimaging. Although this line of research is at an early stage, results indicate that TBI causes a more widely dispersed activation in frontal and posterior cortices. Further progress in analysis of the consequences of TBI on neural structure and function will require control of variability in neuropathology and behavior.

Brain Injuries↗