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Integrating electrophysiology and neuroimaging of spatial selective attention to simple isolated visual stimuli.

Visual-spatial attention involves modulations of activity in human visual cortex as indexed by electrophysiological and functional neuroimaging measures. Prior studies investigating the time course and functional anatomy of spatial attention mechanisms in visual cortex have used higher-order discrimination tasks with complex stimuli (e.g. symbol matching in bilateral stimulus arrays, or letter discrimination), or simple detection tasks but in the presence of complex distracting information (e.g. luminance detection with superimposed symbols as distractors). Here we tested the hypothesis that short-latency modulations of incoming sensory signals in extrastriate visual cortex reflect an early spatially specific attentional mechanism. We sought evidence of attentional modulations of sensory input processing for simple, isolated stimuli requiring only an elementary discrimination (i.e. size discrimination). As in prior studies using complex symbols, we observed attention-related changes in regional cerebral blood flow in extrastriate visual cortex that were associated with changes in event-related potentials at a specific latency range. These findings support the idea that early in cortical processing, spatially-specific attentional selection mechanisms can modulate incoming sensory signals based on their spatial location and perhaps independently of higher-order stimulus form.

Adult↗

Neuroimaging and the progression of epilepsy.

Several lines of evidence can be used to try to answer the question of whether epilepsy is a progressive disease, and whether persistent seizures, or the underlying process itself, cause neuronal injury. The results of clinical studies have been inconclusive. Neuroimaging studies offer a quantitative approach. In patients with temporal lobe epilepsy, structural magnetic resonance imaging (MRI) has shown volume reductions ipsilateral to the epileptic focus in hippocampal and extrahippocampal regions; the former, in cross-sectional studies, increase with increasing epilepsy duration. Other factors associated with increasing hippocampal atrophy include a history of complex or prolonged febrile seizures, and generalized tonic-clonic seizure number. Positron emission tomography (PET) has shown supporting results. However, these studies have been cross-sectional rather than longitudinal. Preliminary results from prospective imaging studies using fluorodeoxyglucose PET and volumetric MRI show that patients with more recent seizure onset are less likely to have hypometabolism or volume loss than those with a long history of epilepsy. Alternate interpretations of these data include a possible progressive effect of epilepsy, or a tendency for patients with structural or functional findings at seizure onset to be more likely to develop uncontrolled epilepsy. In addition to the human studies that have been performed, parallel investigations in animal models using some of the same imaging techniques may help to unravel the factors associated with neuronal injury due to seizures, and aid in interpreting results of clinical studies.

Animals↗

Covert attention increases contrast sensitivity: Psychophysical, neurophysiological and neuroimaging studies.

This chapter focuses on the effect of covert spatial attention on contrast sensitivity, a basic visual dimension where the best mechanistic understanding of attention has been achieved. I discuss how models of contrast sensitivity, as well as the confluence of psychophysical, single-unit recording, and neuroimaging studies, suggest that attention increases contrast sensitivity via contrast gain, an effect akin to a change in the physical contrast stimulus. I suggest possible research directions and ways to strengthen the interaction among different levels of analysis to further our understanding of visual attention.

Action Potentials↗

Neuroimaging studies of postobliteration nidus changes in cerebral arteriovenous malformations treated by gamma knife radiosurgery.

BACKGROUND: Following radiosurgical treatment, the majority of patients with arteriovenous malformations (AVMs) are periodically examined by means of computed tomography (CT) and magnetic resonance imaging (MRI) to assess the attainment of nidus obliterations, as well as adverse radiation effects in the surrounding brain. However, few neuroimaging studies of the long-term results following complete obliterations, confirmed by angiography, have been published to date. METHODS: CT, MRI, magnetic resonance (MR) angiographic and angiographic images, obtained after angiographic confirmation of complete nidus obliteration, were reviewed in 11 AVM patients treated with gamma knife radiosurgery. The period between angiographic confirmation of nidus obliteration and these most recent examinations was 12-84 months (mean, 29 months). RESULTS: In ten patients who were assessed by CT, the obliterated nidus was shown to be isodense (eight cases). A significant time-related decrease in contrast enhancement was observed within 1 to 2 postobliteration years (five/seven cases). Eight patients were evaluated by MRI. On T1-weighted imaging, the nidus was shown to be hypointense (six cases) or a mixture of hypointense and isointense areas (two cases). On T2-weighted imaging, nidus intensity varied more than than observed on T1-weighted imaging, and time-related intensity increases were observed (two/seven cases). No flow-signal void was demonstrated in any of these cases. In four of the seven cases, in which serial postobliteration follow-up MRI studies were conducted, significant gadolinium enhancement persisted 3 years or more after obliteration (maximum of 7 years). No vascular abnormalities were demonstrated in seven patients who were assessed by conventional angiography and/or MR angiography. CONCLUSIONS: Radiosurgery-induced changes in a nidus may continue for several years after angiography has shown complete AVM obliteration.

Adolescent↗

A computer program for sequencing and presenting complex sounds for auditory neuroimaging studies.

This paper describes a computer program, named ASAP (audio sequencing and presentation), that runs on IBM PC compatible hardware with a Microsoft Windows operating system and has been specially designed for facilitating auditory neuroimaging studies. The program's main characteristics are: (1) the ability to generate sequences of complex sounds; (2) an easy-to-use, graphical user interface; (3) full compatibility with Microsoft Windows 95 or later and Windows NT version 4.0 or later software; (4) precise timing of selected sound sequences; (5) the capability of triggering other devices; (6) the capability of being triggered to deliver stimuli; (7) support for both monotic and dichotic sound sequences; and (8) rudimentary support for the simultaneous presentation of pictures/text and sound.

Acoustic Stimulation↗

Mineralization of the basal ganglia: implications for neuropsychiatry, pathology and neuroimaging.

This article examines the evidence for and against the existence of basal ganglia mineralization as a defined clinico-pathological entity. In reviewing the literature on basal ganglia mineralization, this article emphasizes evidence derived from different neuroimaging modalities, genetics, metabolic studies, postmortem series and their possible neuropsychiatric correlates. Relevant articles were collected through Medline and Index Medicus searches. Researchers have encountered multiple difficulties in accepting basal ganglia mineralization as a distinct entity. This syndrome lacks set clinical criteria or a unique etiology; not surprisingly, numerous articles have applied varied definitions. Because many of the reported cases have not been examined postmortem, both the extent and nature of their mineralization remains uncertain. Furthermore, researchers have considered small foci of basal ganglia mineralization a normal phenomenon of aging. However, when brain deposits are extensive, they are associated with a set of age-dependent, progressive clinical symptoms. They include cognitive impairment, extrapyramidal symptoms and psychosis. Most cases are related to abnormalities of calcium metabolism, but rare familial cases of idiopathic origin have been reported. Overabundant mineralization of the brain is judged pathological based on its amount, distribution and accompanying clinical symptoms. Although its relation with calcium dysregulation is well known, modern studies have emphasized abnormalities of iron and dopamine metabolism. The authors suggest that these metabolic abnormalities may link basal ganglia mineralization to psychotic symptomatology.

Basal Ganglia↗

Functional neuroimaging studies of human somatosensory cortex.

Two studies were carried out to assess the applicability of echoplanar fMRI at 3.0 T to the analysis of somatosensory mechanisms in humans. Vibrotactile stimulation of the tips of digits two and five reliably generated significant clusters of activation in primary (SI) and secondary (SII) somatosensory cortex, area 43, the pre-central gyrus, posterior insula, posterior parietal cortex and posterior cingulate. Separation of these responses by digit in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study employed microneurographic techniques in which individual median-nerve mechanoreceptive afferents were isolated, physiologically characterized, and microstimulated in conjunction with fMRI. Hemodynamic responses, observed in every case, were robust, focal, and physiologically orderly. These techniques will enable more detailed studies of the representation of the body surface in human somatosensory cortex, the relationship of that organization to short-term plasticity in responses to natural tactile stimuli, and effects of stimulus patterning and unimodal/cross-modal attentional manipulations. They also present unique opportunities to investigate the basic physiology of the BOLD effect, and to optimize the operating characteristics of two important human functional neuroimaging modalities-high-field fMRI and high-resolution EEG-in an unusually specific and well-characterized neurophysiological setting.

Brain Mapping↗

Neuroimaging and functional outcome of neonatal leukomalacia.

Leukomalacia is a major cause of neurological impairment in the high-risk newborn. It can be identified during the early postnatal period by means of ultrasound (US) imaging of the brain, through the anterior fontanel. Magnetic resonance imaging (MRI) permits an optimal differentiation of brain tissue and of its abnormalities, without resorting to ionizing radiation or intravenous contrast. It is particularly appropriate for following the evolution of leukomalacia, after fontanel closure. Ninety-five fullterm and preterm infants with cystic and non-cystic leukomalacia, documented by US, were clinically followed-up until at least 12 months of corrected age. Thirty-two had a severe neurological outcome (mainly cerebral palsy, sometimes associated with mental retardation and/or cerebral visual impairment). The prognosis was worse in cystic leukomalacia than in prolonged flare. Electroencephalogram (EEG) carried out in the first 2 weeks of life provided valuable indexes of further outcome, especially for US findings of more uncertain prognosis. MRI was carried out at around 12 months of corrected age, by means of an apparatus operating at 0.5 Tesla. The main categories of abnormalities observed were the following: cystic lesions, enlarged ventricles with irregular outlines, delayed myelination, high intensity areas in the long TR (repetition time) images within the white matter, cortical atrophy. MRI findings correlated well with the results of US imaging and often with motor, cognitive and visual impairments. Nevertheless, clinical features cannot be predicted by neuroimaging alone and a comprehensive approach, including longitudinal functional and electrophysiological testing, is highly recommended.

Cognition↗

Use of neuroimaging to detect early brain changes in people at genetic risk for Alzheimer's disease.

The neuropathological and cognitive changes preceding Alzheimer's disease appear to begin subtly decades before symptoms of the disease make the clinical diagnosis obvious. Clinical trials have begun to focus on preventive treatments designed to slow age-related cognitive decline and delay the onset of Alzheimer's disease in people with only mild memory complaints. Because people with few cognitive deficits represent a heterogeneous population, prevention studies require large samples in order to detect active drug effects. To address such challenges, recent neuroimaging studies have focused on middle-aged and older adults with only mild memory complaints and evaluated results according to the major known genetic risk for Alzheimer's disease, the apolipoprotein E-4 (APOE-4) allele. In studies using positron emission tomography during mental rest and functional magnetic resonance imaging during memory task performance, brain patterns differ according to genetic risk and are useful in predicting future decline measures and following disease progression in clinical trials.

Alzheimer Disease↗

Neuroimaging in psychiatry.

The promise of neuroimaging as an aid to diagnosis is discussed, and findings from the most accessible imaging techniques are reviewed. In addition, some of the earliest findings from functional MR imaging and other technologies are presented with several illustrations. Strategies for interpretation, critique of imaging techniques, and review of major findings for brain injury, mood, anxiety, schizophrenia, and attention deficit disorders are offered. Examples of normal and pathologic images illustrate actual cases and examples of the newer imaging technologies.

Attention Deficit Disorder with Hyperactivity↗

Structural and functional neuroimaging findings in substance-related disorders.

Intoxication with alcohol results in depressed global glucose metabolism that continues into the stages of withdrawal and abstinence. The decrease in metabolism, however, is not equal across the brain, with certain regions more affected than others. Such a pattern of disturbance suggests that the effect of alcohol on the brain cannot simply be a nonspecific depressant effect secondary to decreased blood flow or glucose transport into the cells but may be related to the dysfunction of the various neurotransmitter systems. Different authors have suggested the dysfunction to be related to the GABAergic, cholinergic, and dopaminergic systems. Long-term alcoholism is associated with atrophy of several brain regions. The frontal lobes and limbic structures seem to be most vulnerable. The data are encouraging with regard to the normalization in brain metabolism and in size of vulnerable brain regions with continued abstinence. In addition to findings of improvement in cognitive functioning and many health parameters, these findings arm clinicians with further data on the benefits of abstinence in the struggle to aid patients in maintaining their sobriety. Several areas remain to be addressed. In particular, clinicians are in need of data, neuroimaging and otherwise, that serve as prognostic indicators, thus allowing patients at higher risk for relapse to be identified and provided with more intensive treatment. A similar need exists for indicators of diagnostic heterogeneity that would guide the development of more highly tailored treatment regimens for identified subgroups of patients. Currently, we have rudimentary knowledge of the gender differences of the effects of alcohol and cocaine on the brain.

Aging↗

How does the apolipoprotein E genotype modulate the brain in aging and in Alzheimer's disease? A review of neuroimaging studies.

The epsilon 4 allele of apolipoprotein E is a risk factor for Alzheimer's disease, but also a modulator of its clinical picture. In this paper, recent research in neuroimaging of aging and Alzheimer's disease in relation to apolipoprotein E is reviewed, emphasizing the advances but also the controversies. Further, the possible clinicopathological implications of these findings are discussed.

Aging↗

Intracranial hypotension syndrome: neuroimaging in five spontaneous cases and etiopathogenetic correlations.

Intracranial hypotension (IH) is essential or, more frequently, secondary. This syndrome is characterized by severe postural headache and low opening cerebrospinal fluid (CSF) pressure; although other symptoms may exist. In this study five patients are investigated. Neuroimaging showed: on computerized tomography scan (CT), poor visualization of the cerebral sulci with small ventricles; on magnetic resonance imaging (MRI), subdural fluid collections with enhancement on the convexity, along the tentorium and in the upper cervix after administration of contrast medium and downward displacement of the brain. Radionuclide cisternography was normal in the two patients who underwent this treatment as well as the meningeal biopsy in another patient. In all patients the opening CSF pressure was low or unmeasurable. The clinical syndrome spontaneously recovered contextually to normalization of neuroradiological findings. The possible pathogenesis (dural border cell layer tear) was discussed and the importance of diagnostic confirmation with MRI and measurement of CSF pressure when IH is thought to be present was underlined.

Adult↗

Parallel distributed processing neuroimaging in the Stroop task using spatially filtered magnetoencephalography analysis.

Parallel distributed processing neuroimaging in the Stroop color word interference task in five healthy subjects was studied. The total reaction time was set at 650 ms with a time window of 200 ms in steps of 50 ms. Spatially filtered magnetoencephalography analysis, as used in synthetic aperture magnetometry, was used. Neural activation began in the left posterior parietal-occipital area (150-250 ms post-stimulus), followed by the right prefrontal polar area (250-350 ms), the left dorsolateral prefrontal cortex (250-400 ms), and the mid- to lower- primary motor area (350-400 ms). Successive and temporally overlapping activation of various cortical regions were successfully estimated within a short 200 ms time interval, contrary to previous positron emission tomography and fMRI studies.

Adult↗

MR atlas of the baboon brain for functional neuroimaging.

Mathematical co-registration of functional image data (e.g., positron emission tomography, PET) to anatomical magnetic resonance (MR) imaging data allows for objective associations between function and anatomy. Baboons are often used as non-human primate models for functional neuroimaging studies. In this work, a digital MR-based high-resolution atlas of the baboon brain was generated and evaluated for PET. The atlas was generated from six SPGR-MR datasets (centered at mid-sagittal line, AC-PC orientation) that were transformed into the space of one representative MR, averaged and resampled into PET space. The atlas was evaluated by comparing blood flow and dopamine receptor and serotonin transporter binding measures determined using regions-of-interest (ROIs) generated on each individual co-registered MR (ROI(i)) and the atlas-defined ROI template (ROI(ATLAS)). Common ROIs applied to all data included frontal cortex, temporal cortex, thalamus, caudate, putamen and cerebellum. High correlations (r(2)>0.87) were found between the ROI(i) and ROI(ATLAS) data for all radiotracers (linear regression across ROIs for each baboon). The average regression slope values ranged from 0.95 to 1.02 across radiotracers. Lastly, use of the atlas for statistical parametric mapping (SPM) of [15O]water data yielded good agreement with previous ROI(i) results. Overall, the digital MR-based atlas allowed for automatic co-registration, proved useful across a range of PET Studies, and is accessible electronically via the Internet.

Anatomy, Artistic↗

Neuroimaging studies in Rett syndrome.

Neuroimaging is a key instrument for determining structural and in vivo functional status of the brain, non-invasively. Multiple approaches can now determine aspects of anatomic and neurochemical changes in brain, and have been utilized effectively in Rett Syndrome patients to understand the biological basis of this neurodevelopmental disorder. Studies performed at our institute include volumetric analyses of MRI, magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), cerebral blood flow measurements with MRI, and positron emission tomography scans (PET). These studies have provided considerable insight into mechanisms underlying the clinical features of this disease. Volumetric analyses suggest that decreased brain volume in RS results from global reductions in both gray and white matter of the brain. A selective vulnerability of the frontal lobes is evidenced by the preferential reduction of blood flow, increased choline and reduced n-acetyl aspartate (NAA) by MRS, and increased glucose uptake in these same regions as shown by ((18)F)-fluorodeoxyglucose (FDG) PET scans. We hypothesize that the increased glucose uptake relates to increased glutamate cycling in synapses. The resulting neuroexcitotoxic injury to the developing brain contributes to the seizures, behavioral disturbance and respiratory irregularities commonly seen in phases 1 and 2 of this disorder.

Adolescent↗

Neuroimaging in neurotoxicology.

The development of imaging technology over the past 25 years has had a profound impact on the clinical practices of a number of medical disciplines. In this article, the author reviews the various neuroimaging modalities and the neurologic processes that they can address.

Brain↗

Clinical applications of FLAIR, HASTE, and magnetization transfer in neuroimaging.

We review the clinical utility of three commonly used and relatively new magnetic resonance techniques as it pertains to neuroimaging. These techniques include fluid-attenuated inversion-recovery (FLAIR) images, half-Fourier acquisition single-shot turbo spin echo (HASTE) images, and magnetization transfer (MT). These techniques may be used to improve image quality and, in some cases, increase the sensitivity and the specificity of magnetic resonance imaging of the brain and spine.

Central Nervous System↗