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PubMed2001

Neuroimaging in basal ganglia disorders: perspectives for transcranial ultrasound.

Transcranial sonography is a new diagnostic tool, allowing not only the evaluation of cerebral arteries but also the two-dimensional display of the brain parenchyma. In this review we will summarize basics of the application, the ultrasound anatomy of the brain and sonographic findings in some movement disorders. While in normal adults basal ganglia nuclei are hypoechogenic, they are hyperechogenic in certain basal ganglia disorders. In Parkinson's disease, for example, the substantia nigra can be depicted as a distinctly echogenic area. An elevated echogenicity of the lentiform nuclei was noticed in patients with primary adult-onset dystonia. In both disorders the altered echogenicity may arise from higher heavy metal tissue content (i.e. iron in Parkinson's disease and copper in primary dystonia). Our findings converge to the hypothesis that transcranial ultrasound sensitively detects pathological metal accumulation not identified by other neuroimaging techniques (CT and MRI) and therefore provides new insights in the diagnosis of basal ganglia disorders. The implications of these findings for the understanding of the pathogenesis and its usefulness for the early diagnosis of movement disorders are outlined.

Basal Ganglia Diseases↗
PubMed1993

Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology.

Sixty-seven patients with temporal lobe epilepsy without circumscribed, potentially epileptogenic lesions, who were studied with intracranial electrodes and who became seizure free following temporal lobectomy were retrospectively evaluated with regard to preoperative scalp electroencephalographic (EEG) findings, neuropsychological test results, neuroimaging findings, results of surgery, and pathology of resected tissue. Interictal scalp EEG showed paroxysmal abnormalities during prolonged monitoring in 64 patients (96%). These were localized in the anterior temporal region in 60 (94%) of these 64 patients. Bilateral independent paroxysmal activity occurred in 42% of the patients and was preponderant over the side of seizure origin in half. Ictal EEG changes were rarely detected at the time of clinical seizure onset, but lateralized buildup of rhythmic seizure activity during the seizure occurred in 80% of patients. In 13%, the scalp EEG seizure buildup was, however, contralateral to the side of seizure origin as subsequently determined by depth EEG and curative surgery. Lateralized postictal slowing, when present, was a very reliable lateralizing finding. Neuropsychological testing provided lateralizing findings concordant with the side of seizure origin in 73% of patients. When neuropsychological testing produced discordant results or nonlateralizing findings, those patients were usually found to have right temporal seizure origin. Intracarotid amobarbital (Amytal) testing demonstrated absent or marginal memory functions on the side of seizure onset in 63% of patients, but 26 patients (37%) had bilaterally intact memory. In those patients who had magnetic resonance imaging, it was very sensitive in detecting subtle medial temporal abnormalities. These abnormalities were present in 23 of 28 magnetic resonance images, and corresponded with mesial temporal sclerosis on pathological examination in all but 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1997

Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy.

The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.

Adult↗
PubMed2005

Functional neuroimaging in early-onset anorexia nervosa.

Previous neuroimaging studies in early-onset anorexia nervosa provide evidence of limbic system dysfunction. The current study adds support to the possibility by revealing a significant association between unilateral reduction of blood flow in the temporal region and impaired visuospatial ability, impaired visual memory, and enhanced speed of information processing.

Adolescent↗
PubMed2003

Modeling intra-subject correlation among repeated scans in positron emission tomography (PET) neuroimaging data.

Many in vivo positron emission tomography (PET) neuroimaging studies record correlates of regional cerebral blood flow (rCBF) in a series of scans for each individual, usually under different experimental conditions. Typical methods for statistical analysis involve fitting voxel-specific general linear models (GLM) that assume spherical normal errors, implying that all voxel-specific rCBF measurements are independent and arise from identical normal probability distributions. While the spherical GLM provides a unified and computationally efficient approach to estimation, the likely correlations among an individual's repeated scans and heteroscedasticity between conditions prompt the use of extended statistical methodology. We outline a more general method to analyze PET data using random effects and correlated errors to model unequal variances across conditions as well as covariances (correlations) among the repeated scans for each individual. We introduce correlation maps to display intra-subject correlations between an individual's rCBF measurements from different scans. We illustrate the application of our model using data from a study of social anxiety and highlight analytical advantages over the spherical GLM.

Cerebrovascular Circulation↗
PubMed2004

Permutation tests for factorially designed neuroimaging experiments.

Permutation methods for analysis of functional neuroimaging data acquired as factorially designed experiments are described and validated. The F ratio was estimated for main effects and interactions at each voxel in standard space. Critical values corresponding to probability thresholds were derived from a null distribution sampled by appropriate permutation of observations. Spatially informed, cluster-level test statistics were generated by applying a preliminary probability threshold to the voxel F maps and then computing the sum of voxel statistics in each of the resulting three-dimensional clusters, i.e., cluster "mass." Using simulations comprising two between- or within-subject factors each with two or three levels, contaminated by Gaussian and non-normal noise, the voxel-wise permutation test was compared to the standard parametric F test and to the performance of the spatially informed statistic using receiver operating characteristic (ROC) curves. Validity of the permutation-testing algorithm and software is endorsed by almost identical performance of parametric and permutation tests of the voxel-level F statistic. Permutation testing of suprathreshold voxel cluster mass, however, was found to provide consistently superior sensitivity to detect simulated signals than either of the voxel-level tests. The methods are also illustrated by application to an experimental dataset designed to investigate effects of antidepressant drug treatment on brain activation by implicit sad facial affect perception in patients with major depression. Antidepressant drug effects in left amygdala and ventral striatum were detected by this software for an interaction between time (within-subject factor) and group (between-subject factor) in a representative two-way factorial design.

Algorithms↗
PubMed2005

N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies.

One of the most popular experimental paradigms for functional neuroimaging studies of working memory has been the n-back task, in which subjects are asked to monitor the identity or location of a series of verbal or nonverbal stimuli and to indicate when the currently presented stimulus is the same as the one presented n trials previously. We conducted a quantitative meta-analysis of 668 sets of activation coordinates in Talairach space reported in 24 primary studies of n-back task variants manipulating process (location vs. identity monitoring) and content (verbal or nonverbal) of working memory. We found the following cortical regions were activated robustly (voxelwise false discovery rate = 1%): lateral premotor cortex; dorsal cingulate and medial premotor cortex; dorsolateral and ventrolateral prefrontal cortex; frontal poles; and medial and lateral posterior parietal cortex. Subsidiary meta-analyses based on appropriate subsets of the primary data demonstrated broadly similar activation patterns for identity monitoring of verbal stimuli and both location and identity monitoring of nonverbal stimuli. There was also some evidence for distinct frontoparietal activation patterns in response to different task variants. The functional specializations of each of the major cortical components in the generic large-scale frontoparietal system are discussed. We conclude that quantitative meta-analysis can be a powerful tool for combining results of multiple primary studies reported in Talairach space. Here, it provides evidence both for broadly consistent activation of frontal and parietal cortical regions by various versions of the n-back working memory paradigm, and for process- and content-specific frontoparietal activation by working memory.

Brain↗
PubMed2005

Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia.

Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper- and hypoactivation in schizophrenia. We utilize a quantitative meta-analysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal pole regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper- and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia.

Brain↗
PubMed2001

Neuroimaging in headache.

Neuroimaging of primary headache syndromes, such as cluster headache and migraine, has begun to provide a glimpse of the neuroanatomical and physiological basis of the conditions. Although these headache types have been widely described as vascular, there is now considerable imaging and clinical evidence to suggest that they are primarily driven from the brain. The shared anatomical and physiological substrate for both of these clinical problems is the neural innervation of the cranial circulation. Functional imaging with positron emission tomography (PET) has shed light on the genesis of both syndromes, documenting activation in the midbrain and pons in migraine, and in the hypothalamic grey in cluster headache. These areas are involved not simply as a response to first division nociceptive pain impulses but specifically in each syndrome, probably in some permissive or dysfunctional role. In a recent PET study in cluster headache, as well as brain activation, tracer pooled in the region of the major basal arteries. This is likely to be due to vasodilatation of these vessels during the acute pain-attack and represents the first convincing activation of neural vasodilator mechanisms in humans. The author takes the view that the known physiology and pathophysiology of the systems involved dictate that these disorders should be collectively regarded as neurovascular headaches to place emphasis on the interaction between nerves and vessels, which is the underlying characteristic of these syndromes. Understanding this neurovascular relationship facilitates an understanding of the pain mechanisms, while characterising the CNS dysfunction will ultimately allow us to dissect out the basic pathogenesis of these disorders.

Capsaicin↗
PubMedDate not supplied

Neuroimaging in epilepsy.

Neuroimaging techniques have improved the understanding, diagnosis, and management of epilepsy. By providing excellent structural information, MRI is the technique of choice in evaluating patients with epilepsy. Functional imaging techniques, including MR spectroscopy, functional MRI, positron emission tomography, and single photon emission CT, permit noninvasive assessment of the epileptic substrate, its functional status, and neuroreceptors. The MRI-based techniques will potentially assume a greater role in the cost-effective workup of the patient. Currently, newer techniques such as magnetoencephalography, magnetic source imaging, and optical imaging are research tools.

Brain↗
PubMed2005

Clinical applications of neuroimaging with susceptibility-weighted imaging.

Susceptibility-weighted imaging (SWI) consists of using both magnitude and phase images from a high-resolution, three-dimensional, fully velocity compensated gradient-echo sequence. Postprocessing is applied to the magnitude image by means of a phase mask to increase the conspicuity of the veins and other sources of susceptibility effects. This article gives a background of the SWI technique and describes its role in clinical neuroimaging. SWI is currently being tested in a number of centers worldwide as an emerging technique to improve the diagnosis of neurological trauma, brain neoplasms, and neurovascular diseases because of its ability to reveal vascular abnormalities and microbleeds.

Brain↗
PubMed2003

Dopamine transporter: basic aspects and neuroimaging.

The plasma membrane dopamine transporter (DAT) is found exclusively in dopamine neurones and seems to be the defining molecule of the dopamine neurone. It provides effective control over the intensity of dopamine-mediated signalling by recapturing the neurotransmitter released by presynaptic neurones. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) represent unique techniques for assessing in vivo DAT distribution in humans and offer reliable methods for studying nigrostriatal dopaminergic function in health and disease. The characteristics of different DAT radiotracers, the modifying influences of factors such as age, gender, smoking habit, and dopaminergic drugs on DAT transporters as well as their implication in evaluation of neuroimaging studies are discussed.

Animals↗
PubMed2006

Holmes tremor: Application of modern neuroimaging techniques.

Holmes tremor has a characteristic rest, intention, and postural component. The syndrome arises as a consequence of a lesion in the upper brainstem and cerebral peduncles, which, it is postulated, interrupts the cerebello-rubrothalamic pathway. Ataxia, ophthalmoplegia, and bradykinesia are associated features. We present a case of Holmes tremor secondary to a midbrain cavernoma. Modern neuroimaging techniques in this case confirm that a combination of damage to the cerebello-rubrothalamic pathway and the nigrostriatal pathway is required for the full Holmes tremor syndrome to occur.

Adult↗
PubMed2002

Neonatal encephalopathy in the term infant: neuroimaging and inflammatory cytokines.

The interrelationship between inflammation and ischemia is complex and poorly understood in the developing nervous system. In the preterm newborn, maternal infection may predispose to white matter injury and may be associated with cytokine elevation. In the term infant, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. This review discusses the interplay among inflammatory cytokines, neonatal encephalopathy, and neuroimaging parameters.

Brain↗
PubMed2001

Neuroimaging at 1.5 T and 3.0 T: comparison of oxygenation-sensitive magnetic resonance imaging.

Noise properties, the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and signal responses were compared during functional activation of the human brain at 1.5 and 3.0 T. At the higher field spiral gradient-echo (GRE) brain images revealed an average gain in SNR of 1.7 in fully relaxed and 2.2 in images with a repetition time (TR) of 1.5 sec. The tempered gain at longer TRs reflects the fact that the physiological noise depends on the signal strength and becomes a larger fraction of the total noise at 3.0 T. Activation of the primary motor and visual cortex resulted in a 36% and 44% increase of "activated pixels" at 3.0 T, which reflects a greater sensitivity for the detection of activated gray matter at the higher field. The gain in the CNR exhibited a dependency on the underlying tissue, i.e., an increase of 1.8x in regions of particular high activation-induced signal changes (presumably venous vessels) and of 2.2x in the average activated areas. These results demonstrate that 3.0 T provides a clear advantage over 1.5 T for neuroimaging of homogeneous brain tissue, although stronger physiological noise contributions, more complicated signal features in the proximity of strong susceptibility gradients, and changes in the intrinsic relaxation times may mediate the enhancement. Magn Reson Med 45:595-604, 2001.

Brain↗
PubMed2002

Self-administration of cocaine and the cocaine analog RTI-113: relationship to dopamine transporter occupancy determined by PET neuroimaging in rhesus monkeys.

Dopaminergic mechanisms are thought to play a central role in the reinforcing effects of cocaine. The present study examined the reinforcing effects of 3beta-(4-chlorophenyl)tropane-2beta-carboxylic acid phenyl ester (RTI-113), a long-acting, selective, high-affinity dopamine uptake inhibitor. Additionally, the effects of RTI-113 pretreatment on cocaine self-administration were determined. Monkeys were trained to respond under a second-order schedule for intravenous cocaine administration (0.10 or 0.17 mg/kg/infusion). When responding was stable, cocaine (0.0030-1.0 mg/kg/infusion) and RTI-113 (0.010-0.30 mg/kg/infusion) were substituted for the cocaine training dose. Cocaine and RTI-113 were equipotent for their reinforcing effects. However, cocaine maintained higher response rates in two of the three monkeys tested. When administered as a pretreatment, RTI-113 (0.10-0.30 mg/kg) dose-dependently reduced responding maintained by two doses of cocaine. Drug effects on behavior were related to dopamine transporter (DAT) occupancy in monkey striatum during neuroimaging with positron emission tomography. DAT occupancy was determined by displacement of 8-(2-[(18)F]fluroethyl)2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (FECNT). DAT occupancy was between 65-76% and 94-99% for doses of cocaine and RTI-113 that maintained maximum response rates, respectively. DAT occupancy did not differ markedly across RTI-113 pretreatment doses and ranged between 72-84%. The results suggest that the pharmacokinetic profile of RTI-113 (i.e., long-acting) may influence its ability to maintain self-administration, and therefore its abuse liability. Additionally, high DAT occupancy is required for RTI-113 to reduce cocaine-maintained responding.

Animals↗
PubMed1997

Working memory: a view from neuroimaging.

We have used neuroimaging techniques, mainly positron emission tomography (PET), to study cognitively driven issues about working memory. Two kinds of experiments are described. In the first kind, we employ standard subtraction logic to uncover the basic components of working memory. These studies indicate that: (a) there are different working-memory systems for spatial, object, and verbal information (with the spatial system localized more in the right hemisphere, and the verbal system more in the left hemisphere); (b) within at least the spatial and verbal systems, separable components seem to be responsible for the passive storage of information and the active maintenance of information (with the storage component being localized more in the back of the brain, and the maintenance component in the front); and (c) there may be separate components responsible for processing the contents of working memory (localized in prefrontal cortex). In our second kind of experiment we have focused on verbal working memory and incrementally varied one task parameter-memory load-in an effort to obtain a more fine-grained analysis of the system's operations. The results indicate that all relevant components of the system show some increase in activity with increasing memory load (e.g., the frontal regions responsible for verbal rehearsal show incremental increases in activation with increasing memory load). In contrast, brain regions that are not part of the working-memory system show no effect of memory load. Furthermore, the time courses of activation may differ for regions that are sensitive to load versus those that are not. Taken together, our results provide support for certain cognitive models of working memory (e.g., Baddeley, 1992) and also suggest some distinctions that these models have not emphasized. And more fundamentally, the results provide a neural base for cognitive models of working memory.

Brain↗
PubMed1999

Ambiguous results in functional neuroimaging data analysis due to covariate correlation.

In this note we draw attention to a source of potential ambiguity in functional neuroimaging results when data analysis is based on the resolution of a linear model. This ambiguity arises whenever there exists correlation between the model covariates. A single-subject PET activation experiment helps to illustrate to what extent correlation can affect statistical results interpretation, possibly leading to misinterpretation of part of the activation pattern. This note is intended to clarify this point and to suggest the use of a simple and well-known procedure to deal with these situations. In the Appendix, we suggest a convenient mathematical formulation for statistical tests particularly useful in such cases.

Brain↗