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PubMed2005

Functional neuroimaging and electrophysiology biomarkers for clinical trials for cognition in schizophrenia.

"Measurement and Treatment Research to Improve Cognition in Schizophrenia" or MATRICS is a National Institute of Mental Health (NIMH)--sponsored research effort to drive novel drug development for the treatment of cognitive impairments in schizophrenia. On September 9-10, 2004, MATRICS convened representatives from NIMH, academia, and industry for the final of a series of consensus-oriented conferences, with this meeting entitled "New Approaches to Assessing and Improving Cognition in Schizophrenia." In this article, we present a summary of the discussions that focused on functional neuroimaging and electrophysiology biomarkers, outlining the research priorities, which included developing further consensus regarding the cognitive processes that are critical to examine in schizophrenia and the paradigms to examine them, resolving issues of test-retest reliability and discrepant findings in the literature, and additional basic research regarding the methods before fully implementing these paradigms in drug trials. Also summarized are the relative advantages and disadvantages of the different approaches and varying perspectives among the participants regarding these tools. Our hope is that this report will help guide and further stimulate coordinated efforts among researchers, industry, and funding agencies in meeting the urgent need for novel pharmacotherapeutics for cognitive impairments in schizophrenia and useful neurobiological indexes for tracking the resulting improvements in cognitive function.

Cognition Disorders↗
PubMed2000

Functional neuroimaging and quantitative electroencephalography in adult traumatic head injury: clinical applications and interpretive cautions.

Functional neuroimaging and quantitative electroencephalographic procedures are being used increasingly in brain injury research and clinical care. These procedures are also seeing increased use in the context of forensic evaluations, particularly in cases of mild head trauma. This article provides an overview of the use of procedures such as positron emission tomography, single photon emission computed tomography, and quantitative electroencephalogram in adults. Also discussed are the clinical limitations of each procedure within the context of myriad interpretive confounds that can interfere with accurate differential diagnosis of mild head trauma.

Adult↗
PubMed1998

Functional neuroimaging of attention in the auditory modality.

Previous functional neuroimaging studies of attention have emphasized the visual modality. We developed an auditory version of the continuous performance test (CPT) that included simple, focused and divided attention conditions. Positron emission tomographic (PET) scans were acquired during CPT performance in normal young adults and then submitted to statistical parametric mapping. Simple attention brought about a large region of activation involving the anterior cingulate gyrus and the right anterior/mesial frontal lobe. Focused and divided attention CPT conditions were compared but there were few significant differences. The findings are consistent with activation of an anterior attention network during auditory attention, without involvement of posterior attention structures which are more likely to vary in accordance with sensory modality.

Acoustic Stimulation↗
PubMed1998

Physiologic aspects of event related paradigms in magnetic resonance functional neuroimaging.

In order to substantiate event related paradigms in magnetic resonance functional neuroimaging, we assessed the temporal and spatial characteristics of oxygenation-sensitive MRI responses to 1 s periods of visual activation in repetitive protocols. A main finding is a reduction of the functional contrast between conditions (reversing checkerboard vs. darkness) for decreasing interstimulus intervals yielding 4.5% signal change for 89 s, 4% for 9 s, 3% for 6 s, and 1% for 3 s, respectively. Although rapid repetitions of identical stimuli preclude the development of the full positive and negative MRI signal deflections, pertinent responses leave the spatial pattern of activated brain regions unaffected and result in identical maps. These findings suggest the use of interstimulus intervals of the order of the response time from stimulus onset to maximum signal strength (5-6 s in the visual system). The resulting distinction in time will allow for separate mapping of stimulus-related responses with spatially overlapping cortical representations.

Adult↗
PubMed1999

Human cortical gustatory areas: a review of functional neuroimaging data.

In an effort to define human cortical gustatory areas we reviewed functional neuroimaging data for which coordinates standardized in Talairach proportional space were available. We observed a wide distribution of peaks within the insula and parietal and frontal opercula, suggesting multiple gustatory regions within this cortical area. Multiple peaks also emerged in the orbitofrontal cortex. However, only two peaks, both in the right hemisphere, were observed in the caudolateral orbitofrontal cortex, the region likely homologous to the secondary taste area described in monkeys. Overall significantly more peaks originated from the right hemisphere suggesting asymmetrical cortical representation of taste favoring the right hemisphere.

Brain Mapping↗
PubMedDate not supplied

Neuroimaging findings in a suprasellar granular cell tumor.

A 27-year-old woman presented with a history of amenorrhea, visual disturbance, and diabetes insipidus. Magnetic resonance imaging showed a large enhancing suprasellar mass with associated edema involving the left striatum. The lesion was hypometabolic on fluorodeoxyglucose-positron emission tomography. At surgery, a subtotal resection of a vascular tumor that appeared to arise from the posterior pituitary and hypothalamus was carried out. Pathologic examination revealed a granular cell tumor. We report the preoperative neuroimaging findings in this rare posterior pituitary stalk tumor.

Adult↗
PubMed1993

Neuroimaging procedures in acute ischemic stroke.

Recently, neuroimaging procedures have been applied extensively to the acute-stage assessment of ischemic brain damage. Positron emission tomography studies of brain perfusion and oxygen metabolism performed within 18 hours of stroke onset both depict the amount of already irreversibly damaged tissue and accurately predict the subsequent neurologic course in a sizeable fraction of patients. The prognosis is poor in those patients with extensive irreversible damage and good when early spontaneous reperfusion has occurred before cortical damage has been established. The remaining patients, in whom ischemia is still ongoing and the neurological course is unpredictable, may constitute a subgroup more amenable to trials of therapy. New developments in diffusion-weighted magnetic resonance imaging suggest this noninvasive tool, like positron emission tomography, may be sensitive to failure of energy metabolism very soon after ischemia begins. Studies in rats suggest it may be possible to differentiate still salvageable tissue from irreversibly compromised tissue with this technique. Ultra-fast diffusion-weighted magnetic resonance imaging is feasible in humans and preliminary observations suggest the technique is as sensitive in humans as it is in rats. The usefulness in acute stroke management of other magnetic resonance techniques still in development, such as blood volume and perfusion imaging, deoxyhemoglobin-sensitive sequences, and 1H or 31P spectroscopy, remains to be assessed.

Brain↗
PubMed1996

Functional neuroimaging: radiology.

Rapid advances, in respect of the visual and auditory systems, have occurred in neuroimaging over the past year in the area of so-called 'functional imaging', and in particular of functional magnetic resonance imaging. This has been accelerated by the introduction of echo-planar imaging, which allows for the very fast acquisition (< 100 ms/image) of multislice images. Radiology is no longer just a question of interpreting anatomy, for, with the ability to combine structure with function, we are now able to extract physiological information. This opens up exciting possibilities for advances in the field of neuroscience, and functional imaging will therefore form the main thrust of this review.

Auditory Cortex↗
PubMed2000

Neuroimaging correlates of cognitive and functional outcome after traumatic brain injury.

Magnetic resonance imaging (MRI) may provide an estimate of the severity of diffuse axonal injury by quantitative measurements of atrophy of white matter tracts (such as corpus callosum) and of ventricular enlargement (particularly the third ventricle). However, most MRI studies failed to reveal consistent relationships between the pattern of neuropsychological impairments and the site and extent of focal structural lesions after traumatic brain injury. Functional neuroimaging techniques, such as positron emission tomography or functional MRI, may reveal areas of cerebral dysfunction in regions that look structurally intact on MRI. Studies using these techniques have suggested that the cognitive and behavioural disturbances of traumatic brain injury could be related to a defective activation of a prefrontal-cingulate network.

Animals↗
PubMedDate not supplied

Structural anomalies revealed by neuroimaging studies in the brains of patients with neurofibromatosis type 1 and large deletions.

PURPOSE: The basis for cognitive problems in patients with neurofibromatosis type 1 (NF1) is unknown. A subset of NF1 patients with deletion of the entire NF1 gene has severe learning problems or mental retardation. We have reviewed neuroimaging studies (CT and MRI) in five such patients to determine whether structural anomalies in the brain are present and might explain the impaired cognitive function. METHODS: Five patients with NF1 and deletion of the entire gene were identified by FISH studies. A retrospective review was conducted of CT and MRI images, as well as of data from developmental assessments. RESULTS: All five patients had severe developmental impairment. None had been exposed to chemotherapy or radiation therapy. All had multiple regions of bright T2 signal intensity. Structural anomalies were seen in three of the five patients and included callosal dysgenesis in one, septum cavum vergae and pellucidum in two, mega cisterna magna in one, and Chiari I malformation with severe hydrocephalus in one patient. CONCLUSION: Individuals with NF1 and large gene deletions have an increased frequency of structural anomalies of the brain not usually seen in NF1 patients. This suggests that the mental retardation in these individuals is due, at least in part, to abnormal brain development rather than a defect in brain function due to haplosufficiency of the NF1 gene product.

Adolescent↗
PubMed2006

Structural neuroimaging research methods in geriatric depression.

Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, there is evidence that abnormalities in specific brain structures and their interconnections confer vulnerability to the development of late-life depression. Structural magnetic resonance imaging methods can be used to identify and quantify brain abnormalities predisposing to geriatric depression and in prediction of treatment response. This article reviews several techniques, including morphometric approaches, study of white matter hyperintensities, diffusion tensor imaging, magnetization transfer imaging, t2 relaxography, and spectroscopy, that have been used to examine these brain abnormalities with a focus on the type of information obtained by each method as well as each method's limitations. The authors argue that the available methods provide complementary information and that, when combined judiciously, can increase the knowledge gained from neuroimaging findings and conceptually advance the field of geriatric depression.

Aged↗
PubMedDate not supplied

Efficacy of contrast medium use for neuroimaging at 3.0 T: utility of IR-FSE compared to other T1-weighted pulse sequences.

As inversion-recovery (IR) technique improves T1 contrast at high field strength, signal enhancement by T1-shortening contrast media may be affected. To clarify the different enhancement properties at 3.0 T, the authors compared T1-weighted sequences. Twelve contrast-enhancing lesions were investigated by spin-echo (SE), inversion recovery fast spin-echo (IR-FSE), two-dimensional gradient-echo (2D GE), and magnetization-prepared three-dimensional gradient-echo (3D GE) sequences and evaluated by comparing signal-intensity enhancements within the lesions. In addition, signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were measured. On average, signal enhancement of the lesions amounted to 60% for SE, 57% for IR-FSE, 32% for 2D GE, and 35% for 3D GE images. CNR of gray matter versus white matter was significantly higher for IR SE and GE imaging than for genuine SE and 2D GE acquisitions (Wilcoxon test), while 2D GE imaging alone had an excellent SNR. As IR-FSE images provide an excellent CNR for gray and white matter in the brain and contrast enhancement performs almost similarly well compared with SE imaging, this technique appears to be well suited for T1-weighted neuroimaging without and with contrast enhancement at 3.0 T. However, the inherent blurring of the IR-FSE can lead to poor performance for very small lesions.

Adult↗
PubMedDate not supplied

Acute hemorrhagic leukoencephalitis: neuroimaging features and neuropathologic diagnosis.

A case of biopsy-proven acute hemorrhagic leukoencephalitis is reported. The early computed tomography scans showed extensive bilateral hypodensities with mass effects and foci of microhemorrhages. Bilateral asymmetric hyperintensities in the mesiotemporal and frontal lobes and massive edema were found on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images in a pattern classic for herpes simplex encephalitis. This fulminant demyelinating disease progresses to coma and death within days. Early diagnosis with neuroimaging studies and rapid correlation with the clinical findings of this disease are vital for the institution of potentially lifesaving treatments.

Adult↗
PubMed2005

Neuroimaging in drug and substance abuse part I: cocaine, cannabis, and ecstasy.

Multiple neurological complications of cocaine abuse have been described including both ischemic and hemorrhagic cerebrovascular events, atrophy in the case of chronic abuse, and an increase in incidence of congenital malformations in the setting of maternal use. The abuse of cannabis may cause a number of neurovascular changes that, in turn, may result in ischemic events, however, a direct connection between these has not been fully established. The use of MDMA (ecstasy), a popular recreational drug, has been related to ischemic and hemorrhagic cerebrovascular events, as well as atrophy. Neuroimaging studies are vital in the assessment of the extent of neurologic damage in these patients.

Atrophy↗
PubMed2005

Healthy and pathological processes in adult development: new evidence from neuroimaging of the aging brain.

PURPOSE OF REVIEW: Recent research has revealed that the population of older adults is composed not only of individuals who are either healthy or have an age-related disease, most commonly Alzheimer's disease, but also individuals with mild cognitive impairment who are at-risk for or already in the prodromal stage of Alzheimer's disease. These variations in cognitive aging can be related to their neural bases via structural and functional neuroimaging methods. RECENT FINDINGS: Healthy aging appears to primarily affect a frontal-striatal system that undergirds executive control of cognition, while minimally affecting medial temporal lobe structures. Functional imaging studies suggest that enhanced prefrontal engagement may offer compensatory plasticity that minimizes age-related cognitive losses. Mild cognitive impairment appears to affect the entorhinal cortex in particular, with functional consequences in other brain regions. Alzheimer's disease is characterized by severe hippocampal injury, although early-stage Alzheimer's disease may relatively spare some cortical regions. SUMMARY: Advances in in-vivo imaging methods are providing the tools for identifying different trajectories of neurocognitive aging, and knowledge about these brain changes may promote opportunities for treatment.

Age Factors↗
PubMed2006

Seeing is believing: neuroimaging adds to our understanding of cerebral pathology.

PURPOSE OF REVIEW: Recent technological developments in neuroimaging have led to new technologies that provide measures of the cerebral pathology of neurodegeneration in living humans. The purpose of this review is to provide background behind these developments and update readers on new findings. RECENT FINDINGS: Several imaging methods using positron emission tomography have provided measures of amyloid senile plaques in the brain of demented patients and patients with early memory symptoms. ([F-18]FDDNP)-positron emission tomography provides measures of both amyloid plaques and neurofibrillary tangles. Initial results indicate that the pattern of binding values in Alzheimer's disease is consistent with the known neuropathology from autopsy studies, and patients with mild cognitive impairment, who are at risk of Alzheimer's disease, show binding values intermediate between Alzheimer's disease and normal aging. 2-(1-{6-[(2-[F-18]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) positron emission tomography also shows a pattern of neuropathology distribution for frontotemporal dementia that differs from that of Alzheimer's disease. SUMMARY: In-vivo imaging of cerebral pathology offers the potential for more effective and earlier diagnosis and use of these technologies as surrogate markers to test novel treatments aimed at preventing or eliminating cerebral plaque and tangle accumulation.

Aging↗
PubMed2006

Conceptual issues in psychiatric neuroimaging.

PURPOSE OF REVIEW: Psychiatric neuroimaging has made a dramatic impact on the understanding of the brain in mental illness in a relatively brief period of time and continues to be evolving in terms of methodology, analysis and utilization of the combination of techniques. Given the level of sophistication of the techniques and the importance of imaging in current academic psychiatry, it is timely to review its conceptual influence on psychopathology. RECENT FINDINGS: The study will review scientific advances in psychiatric neuromaging, around the themes of functional connectivity, diffusion tensor imaging, magnetoencephalography, modality integration, meta-analyses and mega-analyses of data and discuss recent influential findings in contemporary research. We then focus on more conceptual issues relating to biological psychiatry and its relationship with cognitive neuroscience. We discuss the dominant paradigm of scientific psychopathology, namely cognitive neuropsychiatry and how it relates more broadly to imaging and cognitive science and elaborate on the philosophical positions of the paradigm and how it views abnormal mental states. SUMMARY: We conclude that despite the advances in biological psychiatry and the power of the cognitive neuropsychiatry paradigm, its findings are logically contingent upon psychopathology and the normatively defined terms employed therein.

Biological Psychiatry↗
PubMed1997

The cognitive neuroscience of memory: perspectives from neuroimaging research.

Cognitive neuroscience approaches to memory attempt to elucidate the brain processes and systems that are involved in different forms of memory and learning. This paper examines recent research from brain-damaged patients and neuroimaging studies that bears on the distinction between explicit and implicit forms of memory. Explicit memory refers to conscious recollection of previous experiences, whereas implicit memory refers to the non-conscious effects of past experiences on subsequent performance and behaviour. Converging evidence suggests that an implicit form of memory known as priming is associated with changes in posterior cortical regions that are involved in perceptual processing; some of the same regions may contribute to explicit memory. The hippocampal formation and prefrontal cortex also play important roles in explicit memory. Evidence is presented from recent PET scanning studies that suggests that frontal regions are associated with intentional strategic efforts to retrieve recent experiences, whereas the hippocampal formation is associated with some aspect of the actual recollection of an event.

Animals↗