bluuebunny/crossref_metadata_2025 huggingface dataset:
Bisphosphonate‐associated osteonecrosis of mandibular and maxillary bone
Authors: Migliorati Cesar A. , Schubert Mark M. , Peterson Douglas E. , Seneda Luis Marcelo
Published: May 2005

BACKGROUND

The current report presented 17 patients with cancer with bone metastases and 1 patient with osteopenia who received treatment with bisphosphonates and who subsequently developed osteonecrosis of the mandible and/or maxilla.

METHODS

The authors reviewed information on 18 patients who were referred to oral medicine or oral surgery specialists for evaluation and treatment of mandibular and/or maxillary bone necrosis from June 2002 to September 2004. To be included in the current review, patients must have been treated with either pamidronate or zoledronic acid to control or prevent metastatic disease, or with alendronate for osteoporosis. All patients with cancer had received chemotherapy while receiving bisphosphonate management.

RESULTS

The 17 patients with cancer were receiving active medical care for a malignancy. Cancer treatment included a variety of chemotherapeutic agents. They presented with metastatic disease to bone and were treated intravenously with the bisphosphonates pamidronate or zoledronic acid for a mean time of 25 months (range, 4–41 mos). There were 14 females and 4 males with a mean age of 62 years (range, 37–74 yrs). Malignancies included breast carcinoma (n = 10), multiple myeloma (n = 3), prostate carcinoma (n = 1), ovarian carcinoma (n = 1), prostate carcinoma/lymphoma (n = 1), and breast/ovarian carcinoma (n = 1). One female patient with osteopenia received alendronate. The most common clinical osteonecrosis presentations included infection and necrotic bone in the mandible. Associated events included dental extractions, infection, and trauma. Two patients appeared to develop disease spontaneously, without any clinical or radiographic evidence of local pathology. Despite surgical intervention, antibiotic therapy, hyperbaric oxygen therapy, and topical use of chemotherapeutic mouth rinses, most of the lesions did not respond well to therapy. Discontinuation of bisphosphonate therapy did not assure healing. However, 1 patient with cancer healed after discontinuation of bisphosphonate therapy for 4 months.

CONCLUSIONS

The findings in the patient population combined with recent literature reports suggested that bisphosphonates may contribute to the pathogenesis of the oral lesions. The risk factors and precise mechanism involved in the formation of the osteonecrosis are not known. This condition represents a new oral complication in patients with cancer and can be termed bisphosphonate‐associated osteonecrosis. Lesions in patients with osteoporosis are worrisome and need to be further evaluated. Cancer 2005. © 2005 American Cancer Society.
Rapid immunohistochemistry enhances the intraoperative diagnosis of sentinel lymph node metastases in invasive lobular breast carcinoma
Authors: Leikola Junnu P. , Toivonen Terttu S. , Krogerus Leena A. , von Smitten Karl A. J. , Leidenius Marjut H. K.
Published: May 2005

BACKGROUND

The sensitivity of the intraoperative diagnosis of sentinel lymph node (SLN) micrometastases and the metastases of invasive lobular carcinoma (ILC) is low. The goal of the current study was to assess whether the use of intraoperative, rapid immunohistochistochemistry (IHC) enhances the intraoperative detection of micrometastases and metastases of ILC.

METHODS

The sensitivity of the intraoperative diagnosis of SLN metastasis was evaluated in 438 patients when using rapid IHC with a cytokeratin biomarker. The results were compared with those obtained for 557 patients without rapid IHC but with conventional staining.

RESULTS

For patients with ILC, the sensitivity of the intraoperative diagnosis was 87% (45 of 52) in the IHC group and 66% (39 of 59) in the non‐IHC group (P = 0.02). The sensitivity of the intraoperative diagnosis was similar for patients with other types of invasive cancer regardless of the use of rapid IHC. However, rapid IHC enhanced marginally the intraoperative diagnosis of the smallest micrometastases, isolated tumor cells (P = 0.06).

CONCLUSIONS

Rapid IHC with cytokeratin labeling enhanced the intraoperative diagnosis of SLN metastases in patients with ILC. It may also improve the intraoperative diagnosis of micrometastases. Cancer 2005. © 2005 American Cancer Society.
5‐hydroxytryptamine type‐3 receptor antagonists for chemotherapy‐induced and radiotherapy‐induced nausea and emesis
Authors: Aapro Matti , Blower Peter
Published: May 2005

BACKGROUND

Nausea and emesis as a consequence of chemotherapy or radiotherapy can have an adverse effect on patients' quality of life during cancer treatment and may last for > 5 days after administration. Guidelines suggest that, used at appropriate doses, the 5‐hydroxytryptamine type‐3 (5‐HT3) receptor antagonists—which are considered the antiemetic “gold standard” when they are administered in combination with corticosteroids—demonstrate equivalent efficacy and safety. However, due to financial considerations, these agents often are used at lower doses than recommended.

METHODS

A literature review of relevant publications pertaining to the control of chemotherapy‐induced nausea and emesis and dosing issues of the 5‐HT3 receptor antagonists was undertaken to provide a comprehensive review of dosing issues relevant to the 5‐HT3 receptor antagonists.

RESULTS

The issue of “down dosing” was particularly pertinent because of the nature of the 5‐HT3 receptor antagonist dose‐response curve: A steep dose‐response profile within a narrow dose range suggests that antiemetic control will be lost suddenly after dose deescalation. However, the array of predisposing and confounding patient factors indicates that it is unlikely that a loss of antiemetic control will be apparent across a population; rather, individuals will experience loss of control as the dose is reduced below threshold. Of the 4 5‐HT3 receptor antagonists currently licensed in the United States (granisetron, ondansetron, dolasetron, and palonosetron), ondansetron is used sometimes at lower than optimal doses, and there is evidence to suggest that even the approved oral dose of dolasetron may be suboptimal.

CONCLUSIONS

Suboptimal dosing not only will be detrimental to patients' quality of life but, ultimately, will prove counterproductive in terms of hospital resources, and it will add to the already significant socioeconomic burden associated with cancer therapy. Therefore, the dose of antiemetic agent administered should be sufficiently high to ensure good emesis control across the whole patient population. Cancer 2005. © 2005 American Cancer Society.
Basosquamous carcinoma
Authors: Leibovitch Igal , Huilgol Shyamala C. , Selva Dinesh , Richards Shawn , Paver Robert
Published: May 2005

BACKGROUND

Basosquamous carcinoma (BSC) is a rare tumor defined as a basal cell carcinoma (BCC) differentiating into squamous cell carcinoma (SCC). It is reported to have a high rate of recurrence with standard wide local excision. The aim of the current study was to report a large series of patients with BSC treated with Mohs micrographic surgery (MMS).

METHODS

The prospective, multicenter case series included all patients in Australia treated with MMS for BSC, who were monitored by the Skin and Cancer Foundation Australia between 1993 and 2002.

RESULTS

Most of the 178 tumors (95.6%) were located in the head and neck area. Recurrent tumors occurred in 47.8% of patients. The tumors were diagnosed initially as BCC in 87.4% and as SCC in 12.0% of patients. Perineural invasion was recorded in 7.9% of patients with data available. Most of these (69.0%) were previously recurrent tumors. Of 98 patients who completed a 5‐year follow‐up period after MMS, 4 (4.1%) had disease recurrence.

CONCLUSIONS

The low 5‐year disease recurrence rate of BSC with MMS emphasized the importance of margin‐controlled excision using MMS. Cancer 2005. © 2005 American Cancer Society.
Preparation of an Li0.7Ni0.8Co0.2O2 Electrode Material From a New Li–Co–Ni Mixed‐Citrate Precursor
Authors: Mosqueda Yodalgis , Pérez‐Cappe Eduardo , Aranda Pilar , Ruiz‐Hitzky Eduardo
Published: May 2005

A new chemical route to prepare the mixed oxide Li0.7Ni0.8Co0.2O2, which is a member of the well‐known Li‐Ni‐Co‐O family that is of interest as an electrode material for rechargeable lithium batteries, from a mixed citrate is reported. In a first step the new citrate (NH4)3LiNi0.8Co0.2(C6H5O7)2, is synthesized, which, after thermal decomposition, gives the layered mixed‐oxide phase Li0.7Ni0.8Co0.2O2. This oxide has been characterized by chemical analysis, XRD, FTIR, SEM, and DTA, revealing an “ideal” trigonal α‐NaFeO2 type structure with a well‐ordered distribution of Li and Ni ions in different lattices. Thermoelectric power and four‐point electrical conductivity measurements indicate a nonactivated conductivity mechanism of a small polaron. The Li0.7Ni0.8Co0.2O2 compound prepared by this so‐called “citrate route” has a better reversibility of Li‐insertion in charge–discharge cycles than related phases reported previously. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
RuIII Complexes of Edta and Dtpa Polyaminocarboxylate Analogues and Their Use as Nitric Oxide Scavengers
Authors: Storr Tim , Cameron Beth R. , Gossage Robert A. , Yee Helen , Skerlj Renato T. , Darkes Marilyn C. , Fricker Simon P. , Bridger Gary J. , Davies Nathan A. , Wilson Michael T. , Maresca Kevin P. , Zubieta Jon
Published: May 2005

In this study a series of RuIII complexes, chelated by analogues of ethylenediaminetetraacetic acid (edta) and diethylenetriaminepentaacetic acid (dtpa), were produced and tested for NO scavenging ability. Modifications to the edta and dtpa ligand frameworks were made in an effort to alter the reactivity, aqueous stability and pharmacokinetics of the resulting RuIII complexes. The X‐ray structure of the nitrosyl complex 38 confirms that the RuIII complex 27 reacts with NO to form a linear {Ru–NO}6 complex. The nitrosyl complex [C15H15N4O11Ru] crystallized in the P21/c space group with a = 12.731(3) Å, b = 10.894(2) Å, c = 14.241 (3) Å, β = 107.320(4)°, V = 1885.6(7) Å3, and Z = 4. Kinetic studies on the reactions of 14 (k = 2.38 × 106 M–1 s–1) and 27 (k = 2.30 × 105 M–1 s–1) with NO exemplify the difference in chemical properties obtained by ligand framework manipulation. Binding constants of 14 (KB = 5 × 106 M–1) and 27 (KB = 2 × 105 M–1) with NO were also measured, indicating the tight binding of NO by the RuIII complexes. The activity of the RuIII complexes to scavenge nitric oxide was evaluated using RAW264 murine macrophage cells. Ligand analogues of edta that have a pyridine donor as part of the N,N chelate such as 20 and 24 exhibit similar scavenging activity to the parent compound. Ligand analogues of dtpa that have R groups at the central amine in place of the carboxylic acid such as 31, 34, and 37 are also efficient NO scavengers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Capillary electrophoresis‐laser induced fluorescence analysis of endogenous damage in mitochondrial and genomic DNA
Authors: Wirtz Michaela , Schumann Claus A. , Schellenträger Marc , Gäb Siegmar , vom Brocke Jochen , Podeschwa Michael A. L. , Altenbach Hans‐J. , Oscier David , Schmitz Oliver J.
Published: May 2005

Reactive oxygen molecules are formed in vivo as by‐products of normal aerobic metabolism. All organisms dependent on oxygen are inevitably exposed to these species so that DNA damage can occur in both genomic and mitochondrial DNA (mtDNA). In order to determine endogenous DNA damage we have developed an analytical method that involves the isolation and hydrolysis of genomic DNA or mtDNA, the labeling of modified and unmodified nucleotides and micellar electrokinetic chromatography with laser‐induced fluorescence detection. With this method we have found etheno‐adenine, thymine glycol, uracil, hypoxanthine, and 5‐methylcytosine. These were identified by the addition of internal standards to the genomic or mtDNA. There are a large number of other signals in the electropherograms of mtDNA that we have never found in genomic DNA analysis because they are at lower concentration in the genome. In the DNA of untreated patients with chronic lymphocytic leukemia (CLL), uracil and high levels of etheno‐adenine were found, which can be explained by antioxidant enzyme alterations and oxidative stress in the CLL lymphocytes.
Fractionation of glycoforms of recombinant human erythropoietin by preparative capillary isotachophoresis
Authors: Madajová Vlasta , Šimuničová Eva , Kaniansky Dušan , Marák Jozef , Zelenská Viera
Published: May 2005

This feasibility study deals with the use of preparative capillary isotachophoresis (CITP), operating in a discontinuous fractionation mode, to the separations and isolations of glycoforms of recombinant human erythropoietin (rhEPO). The preparative CITP separations were monitored by capillary zone electrophoresis (CZE) with a hydrodynamically closed separation unit. Such a CZE system, suppressing fluctuations of the migration data linked with fluctuations of EOF and hydrodynamic flow, made possible to evaluate and compare the preparative CITP separations performed within a longer time frame. Preparative CITP, carried out in the separation unit with coupled columns of enhanced sample loadability, separating 100 μg of rhEPO in a run lasting ca. 30 min, gave the production rate higher than 55 ng/s for the rhEPO glycoforms. The preparative separations included valve isolations of the glycoforms from the ITP stack into four or six fractions. Such numbers of the fractions corresponded to typical numbers of the major glycoform peaks as resolved in CZE of rhEPO. With respect to close effective mobilities of the glycoforms and a multicomponent nature of rhEPO, the fractions contained mixtures of glycoforms with the dominant glycoforms enriched 10–100‐fold, relative to the original rhEPO sample.
Characterization of proteins from Spirulina platensis microalga using capillary electrophoresis‐ion trap‐mass spectrometry and capillary electrophoresis‐time of flight‐mass spectrometry
Authors: Simó Carolina , Herrero Miguel , Neusüß Christian , Pelzing Matthias , Kenndler Ernst , Barbas Coral , Ibáñez Elena , Cifuentes Alejandro
Published: May 2005

In this work, a new capillary electrophoresis‐mass spectrometry (CE‐MS) procedure is developed to analyze proteins in Spirulina platensis microalgae. It is demonstrated that a fine optimization of several separation parameters is essential in order to achieve suitable CE‐MS analysis of these proteins in natural extracts from microalgae. Namely, optimization of the composition of the separation buffer, electrospray conditions, and washing routine between runs are required in order to obtain reliable and reproducible CE‐MS analyses of the main proteins found in this microalga (namely, allophycocyanin‐α chain, allophycocyanin‐β, c‐phycocyanin‐α, and c‐phycocyanin‐β). The relative molecular mass of these biopolymers is determined using two different MS instruments coupled to CE, i.e., CE‐ion trap‐MS and CE‐time of flight‐MS (CE‐TOF‐MS). A comparison between the results obtained with both instruments is carried out. The high resolution of the TOF‐MS enables the distinction of small modifications in proteins and, thus, a more accurate mass determination. Interestingly, molecular mass values obtained by both CE‐MS procedures agree very well while these experimental values are only in partial agreement with those theoretically expected (i.e., genetically derived masses). Some protein modifications due to amino acids exchange induced by nucleotide codon mutations are proposed to explain this difference.
Analysis of genomic DNA alterations and mRNA expression patterns in a panel of human pancreatic cancer cell lines
Authors: Gysin Stephan , Rickert Paula , Kastury Kumar , McMahon Martin
Published: May 2005

Genomic alterations influencing the expression and/or activity of tumor suppressors or oncogenes such as KRAS2, CDKN2A, TP53, and DPC4 have been directly implicated in the initiation and progression of human pancreatic adenocarcinoma. In an effort further to systematically characterize the genomic alterations that occur in this disease, we conducted a genome wide analysis of alterations in gene copy number using array‐based comparative genomic hybridization (CGH). For this analysis, we utilized a panel of 25 human pancreatic cancer cell lines derived from either primary or metastatic tumors. This panel also included a metastatic progression series of cell lines derived from COLO 357 cells. Array CGH permitted the identification of alterations in the copy number of genes that might participate in the aberrant behavior of pancreatic cancer cells. In addition, the acquisition of invasive and metastatic potential by derivatives of COLO 357 cells was accompanied by additional focal genomic alterations including point mutations and amplification of KRAS2. To complement the array CGH analysis, we also conducted an analysis of mRNA expression patterns in a subset of these cells using cDNA microarrays. By this means, we identified a set of candidate genes, including those regulated by RAS signaling, that may contribute to the process of cancer cell invasion and metastasis. Supplementary material for this article can be found on the Genes, Chromosomes, and Cancer website at http://www.interscience.wiley.com/jpages/1045–2257/suppmat/index.html. © 2005 Wiley‐Liss, Inc.
Cerebral mechanisms of prosodic sensory integration using low‐frequency bands of connected speech
Authors: Hesling Isabelle , Dilharreguy Bixente , Clément Sylvain , Bordessoules Martine , Allard Michèle
Published: May 2005

Even if speech perception has been reported to involve both left and right hemispheres, converging data have posited the existence of a functional asymmetry at the level of secondary auditory cortices. Using fMRI in 12 right‐handed French men listening passively to long connected speech stimuli, we addressed the question of neuronal networks involved in the integration of low frequency bands of speech by comparing 1) differences in brain activity in two listening conditions (FN, NF) differing in the integration of pitch modulations (in FN, low frequencies, obtained by a low‐pass filter, are addressed to the left ear while the whole acoustic message is simultaneously addressed to the right ear, NF being the reverse position); 2) differences in brain activity induced by high and low degrees of prosodic expression (expressive vs. flat); and 3) effects of the same connected speech stimulus in the two listening conditions. Each stimulus induced a specific cerebral network, the flat one weakening activations which were mainly reduced to the bilateral STG for both listening conditions. In the expressive condition, the specific sensory integration FN results in an increase of the articulatory loop and new recruitments such as right BA6‐44, left BA39‐40, the left posterior insula and the bilateral BA30. This finding may be accounted for by the existence of temporal windows differing both in length and in acoustic cues decoding, strengthening the “asymmetric sampling in time” hypothesis posited by Poeppel (Speech Commun 2003; 41:245–255). Such an improvement of prosodic integration could find applications in the rehabilitation of some speech disturbances. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Parametric analysis of oscillatory activity as measured with EEG/MEG
Authors: Kiebel Stefan J. , Tallon‐Baudry Catherine , Friston Karl J.
Published: May 2005

We assess the suitability of conventional parametric statistics for analyzing oscillatory activity, as measured with electroencephalography/magnetoencephalography (EEG/MEG). The approach we consider is based on narrow‐band power time–frequency decompositions of single‐trial data. The ensuing power measures have a χ2‐distribution. The use of the general linear model (GLM) under normal error assumptions is, therefore, difficult to motivate for these data. This is unfortunate because the GLM plays a central role in classical inference and is the standard estimation and inference framework for neuroimaging data. The key contribution of this work is to show that, in many circumstances, one can appeal to the central limit theorem and assume normality for generative models of power. If this is not appropriate, one can transform the data to render the error terms approximately normal. These considerations allow one to analyze induced and evoked oscillations using standard frameworks like statistical parametric mapping. We establish the validity of parametric tests using synthetic and real data and compare its performance to established nonparametric procedures. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Genetic components of functional connectivity in the brain: The heritability of synchronization likelihood
Authors: Posthuma Danielle , de Geus Eco J.C. , Mulder Elles J.C.M. , Smit Dirk J.A. , Boomsma Dorret I. , Stam Cornelis J.
Published: May 2005

Cognitive functions require the integrated activity of multiple specialized, distributed brain areas. Such functional coupling depends on the existence of anatomical connections between the various brain areas as well as physiological processes whereby the activity in one area influences the activity in another area. Recently, the Synchronization Likelihood (SL) method was developed as a general method to study both linear and nonlinear aspects of coupling. In the present study the genetic architecture of the SL in different frequency bands was investigated. Using a large genetically informative sample of 569 subjects from 282 extended twin families we found that the SL is moderately to highly heritable (41–67%) especially in the alpha frequency (8–13 Hz) range. This index of functional connectivity of the brain has been associated with a number of pathological states of the brain. The significant heritability found here suggests that SL can be used to examine the genetic susceptibility to these conditions. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Attentional modulation of perceptual grouping in human visual cortex: ERP studies
Authors: Han Shihui , Jiang Yi , Mao Lihua , Humphreys Glyn W. , Qin Jungang
Published: May 2005

We sought to identify the neural substrates underlying perceptual grouping, and examined whether the grouping‐related neural activities are modulated by task relevance and attention by recording high‐density event‐related potentials (ERPs). Participants were presented with stimulus arrays, in which local elements were either evenly distributed or grouped into rows or columns by proximity or similarity, and had to discriminate orientations of the perceptual groups, or to identify the colors of dots around stimulus displays or of the fixation cross. We found that proximity grouping was indexed by a positive activity over the medial occipital cortex with a peak latency of about 100 ms after stimulus onset (Pd100), whereas grouping by similarity of shape was reflected in a negative activity with longer latency over the occipito‐temporal areas. Dipole modeling based on a realistic boundary element head model localized the Pd100 to the right calcarine cortex. Moreover, we showed that the grouping‐related activities were weakened when stimulus arrays were of low task relevance and fell outside an attended area of field. The results suggest that human calcarine cortex is engaged in early grouping operations defined by proximity, reinforcing the previous fMRI findings. Moreover, our ERP results indicate that the neural bases underlying perceptual grouping in human visual cortex can be modulated by task relevance and attention as early as 100 ms after sensory stimulation. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Statistical parametric maps in functional imaging: A general linear approach
Authors: Friston K. J. , Holmes A. P. , Worsley K. J. , Poline J.‐P. , Frith C. D. , Frackowiak R. S. J.
Published: May 2005

Statistical parametric maps are spatially extended statistical processes that are used to test hypotheses about regionally specific effects in neuroimaging data. The most established sorts of statistical parametric maps (e.g., Friston et al. [1991]: J Cereb Blood Flow Metab 11:690–699; Worsley et al. [1992]: J Cereb Blood Flow Metab 12:900–918) are based on linear models, for example ANCOVA, correlation coefficients and t tests. In the sense that these examples are all special cases of the general linear model it should be possible to implement them (and many others) within a unified framework. We present here a general approach that accomodates most forms of experimental layout and ensuing analysis (designed experiments with fixed effects for factors, covariates and interaction of factors). This approach brings together two well established bodies of theory (the general linear model and the theory of Gaussian fields) to provide a complete and simple framework for the analysis of imaging data.

The importance of this framework is twofold: (i) Conceptual and mathematical simplicity, in that the same small number of operational equations is used irrespective of the complexity of the experiment or nature of the statistical model and (ii) the generality of the framework provides for great latitude in experimental design and analysis. © 1995 Wiley‐Liss, Inc.
Brain activation associated with visual motion studied by functional magnetic resonance imaging in humans
Authors: McCarthy Gregory , Spicer Mark , Adrignolo Anthony , Luby Marie , Gore John , Allison Truett
Published: May 2005

Localized brain activation in response to moving visual stimuli was studied by functional magnetic resonance imaging (fMRI). Stimuli were 100 small white dots randomly arranged on a visual display. During the Motion condition, the dots moved along random, noncoherent linear trajectories at different velocities. During the Blink condition, the dots remained stationary but blinked on and off every 500 ms. The Motion and Blink conditions continuously alternated with 10 cycles per run and 6–8 runs per experiment. In half of the runs, the starting stimulus condition was Motion, while in the remaining runs it was Blink.

A series of 128 gradient echo echoplanar images were acquired from 5–7 slices during each run using a 1.5 T GE Signa with an Advanced NMR echoplanar subsystem. The time series for each voxel were analyzed in the frequency domain. Voxels which demonstrated a significant spectral peak at the alternation frequency and whose phase changed in response to stimulus order were considered activated. These activated voxels were displayed upon high resolution anatomical images to determine the sites of activation and were also transformed into the coordinates of Talairach and Tournoux ([1988] Co‐planar Stereotaxic Atlas of the Human Brain, New York: Thieme) for comparison to prior neuroimaging studies.

Seven of ten subjects showed clusters of activation bilaterally at the junction of the temporal and occipital lobes (area 37) in response to moving stimuli. Most activated voxels were located within or adjacent to a region designated the parietal‐temporal‐occipital fossa, or PTOF. Five subjects also showed activation to moving stimuli in midline occipital cortex. The activated voxels in midline cortex had a significantly shorter phase delay in their MR signal change relative to voxels in PTOF. © 1995 Wiley‐Liss, Inc.1

This article is a US Government work and, as such, is in the public domain in the United States of America
The underestimated cerebellum
Authors: Leiner Henrietta C. , Leiner Alan L. , Dow Robert S.
Published: May 2005

New evidence on the structure and function of the cerebellum, which is summarized in this review, is beginning to clarify the role of the cerebellum in the human brain. The new evidence challenges the traditional concept that the cerebellum serves essentially as a motor mechanism. Instead, a more powerful role is suggested in which the cerebellum contributes to other functions as well, by sending its output to other locations in the cerebral cortex besides the well‐known motor areas. Structural evidence about the cerebellar output to such cerebral targets was obtained by using a new anatomical tracing technique on the monkey, which shows that the cerebellum sends a significant projection of nerve fibers to cognitive areas of the prefrontal cortex. Congruent with this anatomical evidence is the neuroimaging evidence obtained on normal human brains, which shows that the cerebellum is strongly activated when the brain performs some cognitive and language functions. Both structurally and functionally, therefore, the cerebellum is underestimated when it is regarded solely as a motor mechanism. Instead, it can be regarded as a more versatile information‐processing mechanism whose circuitry carries out two basic processes that are commonly performed by computers: (1) the cerebellar circuitry performs transformations on the streams of information flowing into it, and (2) it distributes the transformed streams to the right places in the brain at the right time. When such processing is performed repeatedly on motor, or cognitive, or language tasks, the cerebellum and its cerebral targets can learn through practice to perform these tasks automatically, thereby improving the speed of performance. This speed is needed, for example, in learning to speak a language fluently because such fluency requires a very rapid selection of words, which can be achieved if the search process for finding the words is performed automatically in the brain. We suggest to brain‐mappers that new discoveries about these language and cognitive functions can be found by imaging those parts of the cerebro‐cerebellar system that evolved uniquely in the human brain, and we indicate where to look. © 1995 Wiley‐Liss, Inc.
Topography of diprenorphine binding in human cingulate gyrus and adjacent cortex derived from coregistered PET and MR images
Authors: Vogt Brent A. , Watanabe Hiroshi , Grootoonk Sylke , Jones Anthony K. P.
Published: May 2005

Positron emission tomography (PET) studies of ligand binding lack sufficient anatomical detail to evaluate topographical variations in binding within each of the lobes of the human cerebral cortex. This study employed PET to localize [11C]diprenorphine binding to opioid receptors and magnetic resonance (MR) imaging for defining medial surface structures. Continuous arterial sampling for metabolite corrected [11C]diprenorphine levels and CNS blood flow were used to model the volume of distribution (VDtot) of binding for three subjects. The PET images of VDtot were coregistered to the MR images for each case and 37 regions of interest were used to calculate VDtot. The VDtot was averaged for the three cases and coregistered with an MR reconstruction of the medial surface and plotted onto a flat map of this region.

The average VDtot showed that binding was highest in anterior cingulate, rostral cingulofrontal transition, and prefrontal cortices, while binding in caudal parts of anterior cingulate and superior frontal cortices, and posterior cingulate cortex varied from high to low. Three statistical levels of binding were defined in relation to the high binding in perigenual area 24: high and equal to area 24, moderate and significantly lower than area 24 (p <0.01), or low (p <0.001). These levels of binding were plotted onto an unfolded map of the medial cortex. The VDtot was high in rostral cortex, and a strip of high binding continued caudally on the dorsal lip of the cingulate gyrus. There were patches of high binding in cinguloparietal transition, posterior parietal, and supplementary motor cortices. Four regions had low binding: (1) areas 29 and 30 in the callosal sulcus, (2) fundus of the cingulate sulcus likely involving the cingulate motor areas, (3) fundus of the superior cingulate sulcus involving two divisions of supplementary motor cortex, and (4) sensorimotor cortex on the paracentral lobule. Variations in binding may reflect functional specializations such as low binding in the cingulate motor and visuospatial areas and high levels in areas involved in processing information with affective content. The higher sensitivity of three‐dimensional scanning and coregistration of PET and MR images makes it feasible to analyze single individuals and, by performing pixel‐by‐pixel spectral analysis and generation of parametric maps, statistical analyses are possible. © 1995 Wiley‐Liss, Inc.
Simultaneous functional magnetic resonance imaging and electrophysiological recording
Authors: Huang‐Hellinger Frank R. , Breiter Hans C. , McCormack Glen , Cohen Mark S. , Kwong Ken K. , Sutton Jeffrey P. , Savoy Robert L. , Weisskoff Robert M. , Davis Timothly L. , Baker John R. , Belliveau John W. , Rosen Bruce R.
Published: May 2005

The purpose of this study was to develop a method for obtaining simultaneous electrophysiological and functional magnetic resonance imaging data. Using phantom experiments and tests on several of the investigators, a method for obtaining simultaneous electrophysiological and fMRI data was developed and then tested in three volunteers including two task activation experiments. It was then applied in a sleep experiment (n = 12). Current limiting resistance and low‐pass filtering were added to the electrophysiological circuit. Potential high frequency current loops were avoided in the electrical layout near the subject. MRI was performed at 1.5 T using conventional and echo planar imaging sequences. There was no evidence of subject injury. Expected correlations were observed between the electrophysiological and fMRI data in the task activation experiments. The fMRI data were not significantly degraded by the electrophysiological apparatus. Alpha waves were detected from within the magnet in seven of the 15 experimental sessions. There was degradation of the electrophysiological data due to ballistocardiographic artifacts (pulsatile whole body motion time‐locked to cardiac activity) which varied between subjects from being minimal to becoming large enough to make detection of alpha waves difficult. We concluded that simultaneous fMRI and electrophysiological recording is possible with minor modifications of standard electrophysiological equipment. Our initial results suggest this can be done safely and without compromise of the fMRI data. The usefulness of this technique for studies of such things as sleep and epilepsy is promising. Applications requiring higher precision electrophysiological data, such as evoked response measurements, may require modifications based on ballistocardiographic effects. © 1995 Wiley‐Liss, Inc.
In vivo imaging of neuromodulation using positron emission tomography: Optimal ligand characteristics and task length for detection of activation
Authors: Morris Evan D. , Fisher Ronald E. , Alpert Nathaniel M. , Rauch Scott L. , Fischman Alan J.
Published: May 2005

Considerable evidence suggests that cognitive state affects local levels of neurotransmitter in the brain. We introduce a compartment model of neuroreceptor ligand kinetics to describe the effect of change in cognitive state on positron emission tomography (PET) signal dynamics. The model is used to establish optimal experimental conditions, timing of activation, and ligand characteristics, for detecting cognitive activation. The model, which follows free and bound endogenous neurotransmitter, describes the PET curve predicted for a single injection of radioligand in the presence or absence of activation. Activation was conceptualized as the performance of a task that raises the level of neurotransmitter that competes for receptor sites with the radioligand. Simulating the dopamine system, for example, required making assumptions regarding the kinetic rate constants for binding/dissociation of endogenous dopamine to/from the receptor and dopamine concentrations in the synapse. Simulations suggest that activation of dopamine should be detectable with PET and the D2 receptor ligand [11C]raclopride, although this ligand might not be optimal. Aspects of experimental design can be modified to optimize the likelihood of detecting neurotransmitter changes. The ideal radioligand for these studies should bind irreversibly to its receptor. Furthermore, the task should commence at injection time and last for at least 7 minutes. Optimal task duration depends on the dynamics of free radioligand in the tissue and can be determined via model simulations for any well‐characterized receptor ligand. Flow effects were shown to be distinguishable from those of neurotransmitter activation. General principles regarding desirable ligand characteristics and activation timing held for both the D2 receptor and the dopamine transporter site. © 1995 Wiley‐Liss, Inc.
Hemispheric differences in neural systems for face working memory: A PET‐rCBF study
Authors: Haxby James V. , Ungerleider Leslie G. , Horwitz Barry , Rapoport Stanley I. , Grady Cheryl L.
Published: May 2005

Neural systems that participate in working memory for faces were investigated in an experiment designed to distinguish face perception areas from working memory areas. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) while subjects performed a sensorimotor control task, a face perception control task, and five working memory tasks with parametrically varied retention intervals, ranging from 1 to 21 sec. Striate and ventral occipitotemporal extrastriate areas demonstrated a simple negative correlation between rCBF and retention delay, indicating that these areas participate principally in perceptual operations performed during visual stimulation. By contrast, right and left frontal areas demonstrated rCBF increases that were significantly more sustained across delays than were increases in ventral extrastriate areas, but the relation between rCBF and retention interval differed significantly by hemisphere. Whereas right frontal rCBF showed a nonsignificant tendency to diminish at longer delays, left inferior frontal, middle frontal, and anterior cingulate cortex, as well as left parietal and inferior temporal cortex, demonstrated their largest rCBF increases at the longest delays. These results indicate that right frontal and left frontal, parietal, and temporal areas all participate in face working memory, but that left hemisphere areas are associated with a more durable working memory representation or strategy that subjects rely on increasingly with longer retention intervals. One possible explanation for this hemispheric difference is that left hemisphere activity is associated with a face representation that embodies the result of more analysis and elaboration, whereas right frontal activity is associated with a simpler, icon‐like image of a face that is harder to maintain in working memory. © 1995 Wiley‐Liss, Inc.
A functional magnetic resonance imaging study of cortical regions associated with motor task execution and motor ideation in humans
Authors: Leonardo Marc , Fieldman Jordan , Sadato Norihiro , Campbell Gregory , Ibañez Vicente , Cohen Leonardo , Deiber Marie‐Pierre , Jezzard Peter , Pons Tim , Turner Robert , Le Bihan Denis , Hallett Mark
Published: May 2005

Although motor performance may be enhanced through mental practice, the neurophysiological substrate of mental stimulation (ideation) of a motor task is not well established. We used blood oxygen level‐dependent contrast echo planar imaging at 1.5 T to identify regions of increased neural activity during the performance and ideation of a motor task. Five subjects performed a sequential finger‐to‐thumb opposition task and also imagined themselves performing the task in the absence of actual muscle movement. In all subjects, the left primary sensorimotor cortex showed more activation with actual movement than with motor ideation, but two subjects had significant activation with motor ideation. The left premotor area showed comparable activation with both actual and imagined performance in three subjects. These findings support the involvement of the primary motor area as well as the premotor area in motor ideation. © 1995 Wiley‐Liss, Inc.
Regional cerebral blood flow during object naming and word reading
Authors: Bookheimer Susan Y. , Zeffiro Thomas A. , Blaxton Teresa , Gaillard William , Theodore William
Published: May 2005

By several accounts, reading single words may be accomplished either by sequentially transcribing orthographic units into their corresponding sounds (an indirect route), or by directly associating a visual word form to the semantic or articulatory representation (a direct route). By contrast, the similar task of naming objects must rely only on a direct route, since objects cannot be “sounded out.” To study the localization of cognitive processes specific to reading, we used positron emission tomography (PET) to measure regional cerebral blood flow while subjects named words and pictures of objects silently or aloud. Group averages of blood flow changes were obtained for experimental vs. control tasks. Object and word presentations elicited similar blood flow increases in extra‐striate visual cortices compared with a visual noise control. Silent reading invoked a neural network very similar to that seen when subjects named objects silently, consistent with a “direct” route. Naming objects aloud produced the addition of motor output regions to this network. By contrast, oral reading produced a markedly different pattern of activated regions, suggesting reliance on a separate phonological pathway. These results provide support for the dual coding hypothesis in reading and challenge the use of strict hierarchical models of cognitive operations in PET activation studies. © 1995 Wiley‐Liss, Inc.
Identifying objects at different levels of hierarchy: A positron emission tomography study
Authors: Kosslyn Stephen M. , Alpert Nathaniel M. , Thompson William L.
Published: May 2005

Subjects decided whether names were appropriate for accompanying pictures while their local cerebral blood flow was monitored using positron emission tomography (PET); in one condition, the names were at the “entry” level (i.e., the level spontaneously named, as in “bird” for a robin), in another condition they were at a superordinate level (e.g., “animal”), and in another they were at a subordinate level (e.g., “robin”). The results indicated that different processes are used to evaluate terms at the different levels of analysis. Specifically, there was evidence that memory search is used to evaluate superordinates, but one must collect additional perceptual information to evaluate subordinates. In addition, in another condition the subjects saw written words that named the entry‐level term and decided whether the object could be named by superordinate terms. Similar, but not identical, activation was observed as was found when subjects evaluated superordinate terms for pictures. © 1995 Wiley‐Liss, Inc.
Cortical fields participating in spatial frequency and orientation discrimination: Functinal anatomy by positron emission tomography
Authors: Gulyás Balázs , Roland Per E.
Published: May 2005

With the purpose of localising those anatomical structures participating in the discrimination of spatial frequencies and orientations of gratings, we measured regional cerebral blood flow (rCBF) changes with positron emission tomography (PET) and 15O‐butanol as tracer in ten healthy young male volunteers. The subjects performed two‐alterative forced‐choice discriminations of pairs of squarewave gratings regarding their spatial frequencies or orientations (spatial frequency and orientation tasks) or pairs of a grating and a two‐dimensional random noise pattern regarding the presence or absence of grating pattern (reference task). In both the spatial frequency and orientation discrimination tasks a widely distributed network of functional fields is activated in the occipital, temporal, parietal, and frontal cortices and in the cerebellum. Spatial frequency discrimination required the activation of more cortical fields than orientation discrimination, and whereas the total volume of activated fields in temporal and frontal lobes were similar in the two tasks, the volumes of activated fields in the occipital lobes as well as in the parietal lobes were about two and a half times larger in spatial frequency discrimination than in orientation discrimination. The two networks of cortical fields were partially overlapping in the two tasks. The findings indicate that the discrimination of spatial frequency and orientation signals engages functional networks of cortical fields widely distributed in the human brain. Whereas both the occipito‐temporal and occipito‐parietal visual pathways are involved in both tasks, the processing and analysis of spatial frequency information activates occipital and parietal lobe regions more extensively than those of orientation information. © 1995 Wiley‐Liss, Inc.
Regional cerebral activity associated with the incidental processing of pseudo‐words
Authors: Frith C. D. , Kapur N. , Friston K. J. , Liddle P. F. , Frackowiak R. S. J.
Published: May 2005

In order to study brain activity associated with “incidental” cognitive processing, regional cerebral blood flow (rCBF) was measured in six volunteers while they monitored a sequence of pseudo‐words (e.g., FLOPE) for the rare occasions when the letters were displayed in blue rather than white. In the control condition, the same pseudo‐word was presented repeatedly. In one experimental condition all 60 pseudo‐words were different, while in the other there were 18 repetitions. Although it was not necessary to “read” the pseudo‐words to perform the monitoring task, subsequent forced choice recognition memory for these stimuli was significantly greater than chance. Furthermore, there were significant differences in blood flow between the three conditions. When different pseudo‐words were presented there was significantly greater activity in brain areas concerned with shape and object identity (extrastriate cortex bilaterally), with visual word form (left inferior temporal gyrus), and with articulatory word form (Broca's area) even though none of this information about the pseudo‐words was needed for performance of the monitoring task. In the condition in which some of the words were repeated, there was significantly reduced activity in the right lingual gyrus. This area may therefore be a possible anatomical locus for repetition priming with verbal stimuli. These results indicate the importance of taking into account incidental processing when designing tasks for functional imaging experiments. © 1995 Wiley‐Liss, Inc.
Spatial registration and normalization of images
Authors: Friston Karl. J. , Ashburner J. , Frith C. D. , Poline J.‐B. , Heather J. D. , Frackowiak R. S. J.
Published: May 2005

This paper concerns the spatial and intensity transformations that map one image onto another. We present a general technique that facilitates nonlinear spatial (stereotactic) normalization and image realignment. This technique minimizes the sum of squares between two images following nonlinear spatial deformations and transformations of the voxel (intensity) values. The spatial and intensity transformations are obtained simultaneously, and explicitly, using a least squares solution and a series of linearising devices. The approach is completely noninteractive (automatic), nonlinear, and noniterative. It can be applied in any number of dimensions.

Various applications are considered, including the realignment of functional magnetic resonance imaging (MRI) time‐series, the linear (affine) and nonlinear spatial normalization of positron emission tomography (PET) and structural MRI images, the coregistration of PET to structural MRI, and, implicitly, the conjoining of PET and MRI to obtain high resolution functional images. © 1995 Wiley‐Liss, Inc.