Tissue sodium content in patients with systemic lupus erythematosus: association with disease activity and markers of inflammation.

OBJECTIVES: Sodium (Na+) is stored in the skin and muscle and plays an important role in immune regulation. In animal models, increased tissue Na+ is associated with activation of the immune system, and high salt intake exacerbates autoimmune disease and worsens hypertension. However, there is no information about tissue Na+ and human autoimmune disease. We hypothesized that muscle and skin Na+ content is (a) higher in patients with systemic lupus erythematosus (SLE) than in control subjects, and (b) associated with blood pressure, disease activity, and inflammation markers (interleukin (IL)-6, IL-10 and IL-17 A) in SLE. METHODS: Lower-leg skin and muscle Na+ content was measured in 23 patients with SLE and in 28 control subjects using 23Na+ magnetic resonance imaging. Demographic and clinical information was collected from interviews and chart review, and blood pressure was measured. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Plasma inflammation markers were measured by multiplex immunoassay. RESULTS: Muscle Na+ content was higher in patients with SLE (18.8 (16.7-18.3) mmol/L) than in control subjects (15.8 (14.7-18.3) mmol/L; p < 0.001). Skin Na+ content was also higher in SLE patients than in controls, but this difference was not statistically significant. Among patients with SLE, muscle Na+ was associated with SLEDAI and higher concentrations of IL-10 after adjusting for age, race, and sex. Skin Na+ was significantly associated with systolic blood pressure, but this was attenuated after covariate adjustment. CONCLUSION: Patients with SLE had higher muscle Na+ content than control subjects. In patients with SLE, higher muscle Na+ content was associated with higher disease activity and IL-10 concentrations.

Incorporation of diffusion-weighted magnetic resonance imaging data into a simple mathematical model of tumor growth.

We build on previous work to show how serial diffusion-weighted MRI (DW-MRI) data can be used to estimate proliferation rates in a rat model of brain cancer. Thirteen rats were inoculated intracranially with 9L tumor cells; eight rats were treated with the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea and five rats were untreated controls. All animals underwent DW-MRI immediately before, one day and three days after treatment. Values of the apparent diffusion coefficient (ADC) were calculated from the DW-MRI data and then used to estimate the number of cells in each voxel and also for whole tumor regions of interest. The data from the first two imaging time points were then used to estimate the proliferation rate of each tumor. The proliferation rates were used to predict the number of tumor cells at day three, and this was correlated with the corresponding experimental data. The voxel-by-voxel analysis yielded Pearson's correlation coefficients ranging from −0.06 to 0.65, whereas the region of interest analysis provided Pearson's and concordance correlation coefficients of 0.88 and 0.80, respectively. Additionally, the ratio of positive to negative proliferation values was used to separate the treated and control animals (p <0.05) at an earlier point than the mean ADC values. These results further illustrate how quantitative measurements of tumor state obtained non-invasively by imaging can be incorporated into mathematical models that predict tumor growth.

Using high-resolution MR imaging at 7T to evaluate the anatomy of the midbrain dopaminergic system.

BACKGROUND AND PURPOSE: Dysfunction of DA neurotransmission from the SN and VTA has been implicated in neuropsychiatric diseases, including Parkinson disease and schizophrenia. Unfortunately, these midbrain DA structures are difficult to define on clinical MR imaging. To more precisely evaluate the anatomic architecture of the DA midbrain, we scanned healthy participants with a 7T MR imaging system. Here we contrast the performance of high-resolution T2- and T2*-weighted GRASE and FFE MR imaging scans at 7T. MATERIALS AND METHODS: Ten healthy participants were scanned by using GRASE and FFE sequences. CNRs were calculated among the SN, VTA, and RN, and their volumes were estimated by using a segmentation algorithm. RESULTS: Both GRASE and FFE scans revealed visible contrast between midbrain DA regions. The GRASE scan showed higher CNRs compared with the FFE scan. The T2* contrast of the FFE scan further delineated substructures and microvasculature within the midbrain SN and RN. Segmentation and volume estimation of the midbrain SN, RN, and VTA showed individual differences in the size and volume of these structures across participants. CONCLUSIONS: Both GRASE and FFE provide sufficient CNR to evaluate the anatomy of the midbrain DA system. The FFE in particular reveals vascular details and substructure information within the midbrain regions that could be useful for examining structural changes in midbrain pathologies.

Selective potentiation of the metabotropic glutamate receptor subtype 2 blocks phencyclidine-induced hyperlocomotion and brain activation.

Previous preclinical and clinical studies have demonstrated the efficacy of group II metabotropic glutamate receptor (mGluR) agonists as potential antipsychotics. Recent studies utilizing mGluR2-, mGluR3-, and double knockout mice support that the antipsychotic effects of those compounds are mediated by mGluR2. Indeed, biphenyl indanone-A (BINA), an allosteric potentiator of mGluR2, is effective in experimental models of psychosis, blocking phencyclidine (PCP)-induced hyperlocomotion and prepulse inhibition deficits in mice. In this study, we administered the NMDA receptor antagonist PCP (5.6 mg/kg i.p.) to rats, an established animal model predictive of schizophrenia. Here, we show that BINA (32 mg/kg i.p.) attenuated PCP-induced locomotor activity in rats. Using behaviorally relevant doses of BINA and PCP, we performed pharmacological magnetic resonance imaging (phMRI) to assess the specific brain regions that underlie the psychotomimetic effects of PCP, and examined how BINA modulated the PCP-induced functional changes in vivo. In anesthetized rats, acute administration of PCP produced robust, sustained blood oxygenation level-dependent (BOLD) activation in specific cortical, limbic, thalamic, and striatal regions. Pretreatment with BINA suppressed the amplitude of the BOLD response to PCP in the prefrontal cortex, caudaute-putamen, nucleus accumbens, and mediodorsal thalamus. Our results show key brain structures underlying PCP-induced behaviors in a preclinical model of schizophrenia, and, importantly, its reversal by potentiation of mGluR2 by BINA, revealing specific brain regions functionally involved in its pharmacological action. Finally, our findings bolster the growing body of evidence that mGluR2 is a viable target for the treatment of schizophrenia.

Intra- and inter-subject variability of high field fMRI digit maps in somatosensory area 3b of new world monkeys.

This study evaluates the intra- and inter-subject variability of digit maps in area 3b of anesthetized squirrel monkeys. Maps were collected using high field blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). BOLD responses to individual digit stimulations were mapped and their response properties (location, area of activation, % signal change, time to peak response) were compared within and across imaging sessions separated by up to 20 months. During single digit stimulation using a block design, the spatiotemporal response of the BOLD signal for individual runs within and across sessions and animals was well conserved, with a time to peak BOLD response of 20+/-4 s. The variability in the center of BOLD activation in area 3b was 0.41+/-0.24 mm (mean+/-SD) across individual 5-7 min runs within a scanning session and 0.55+/-0.15 mm across sessions. The average signal change across all animals, runs and sessions was 0.62+/-0.38%, and varied 32% within and 40% across sessions. In a comparison of the stability and reproducibility of the area of single digit activation obtained using three approaches, use of a fixed statistical threshold (P<10(-5)) yielded an average area of 4.8+/-3.5 mm(2) (mean+/-SD), adaptive statistical thresholding 1.32+/-1.259 mm(2) (mean+/-SD), and combined fixed statistical and adaptive BOLD signal amplitude 4.4+/-2.5 mm(2) (mean+/-SD) across image runs and sessions. The somatotopic organization was stable within animals across sessions, while across animals, there was some variation in overall activation pattern and inter-digit distances. These results confirm that BOLD activation maps of single digits in area 3b as characterized by activation center, signal amplitudes, and temporal profile are very stable. The activation sizes determined by various criteria are the most variable measure in this preparation, but adaptive statistical thresholding appears to yield the most stable and reproducible maps. This study serves as a baseline assessment of the limits imposed on the detection of plastic changes by experimental variations of the digit BOLD fMRI activation maps in normal animals, and as an indicator of the likely performance limits in human studies.

A theoretical framework to model DSC-MRI data acquired in the presence of contrast agent extravasation.

Dynamic susceptibility contrast (DSC) MRI methods rely on compartmentalization of the contrast agent such that a susceptibility gradient can be induced between the contrast-containing compartment and adjacent spaces, such as between intravascular and extravascular spaces. When there is a disruption of the blood-brain barrier, as is frequently the case with brain tumors, a contrast agent leaks out of the vasculature, resulting in additional T(1), T(2) and T*(2) relaxation effects in the extravascular space, thereby affecting the signal intensity time course and reducing the reliability of the computed hemodynamic parameters. In this study, a theoretical model describing these dynamic intra- and extravascular T(1), T(2) and T*(2) relaxation interactions is proposed. The applicability of using the proposed model to investigate the influence of relevant MRI pulse sequences (e.g. echo time, flip angle), and physical (e.g. susceptibility calibration factors, pre-contrast relaxation rates) and physiological parameters (e.g. permeability, blood flow, compartmental volume fractions) on DSC-MRI signal time curves is demonstrated. Such a model could yield important insights into the biophysical basis of contrast-agent-extravasation-induced effects on measured DSC-MRI signals and provide a means to investigate pulse sequence optimization and appropriate data analysis methods for the extraction of physiologically relevant imaging metrics.

Optimization of MAGIC gel formulation for three-dimensional radiation therapy dosimetry.

Polymer gel dosimetry aims to provide three-dimensional images of radiation therapy dose distributions in irradiated aqueous gels. The first gels required manufacture in an oxygen-free environment, but later the MAGIC formulation was introduced, which could be made in normal atmospheric conditions. Here we report our studies of the effects of variations in the composition of the MAGIC gel performed in order to optimize its performance over the useful dose range of 0 to 20 Gy. A new formulation (termed 'MAGIC-2') is comprised of 87% water, 4% methacrylic acid, 9% gelatin, 17.38 x 10(-6) M Cu(2+) and a molar ratio of ascorbic acid to [Cu(2+)] of 1000:1. MAGIC-2 has a dose-response slope-to-intercept ratio that is 78% greater than the original formulation and other more favorable properties.

Detection of radiation effects in polymer gel dosimeters using 129Xe NMR.

Polymer gel dosimeters consist of monomers, with or without cross-linking agents, dispersed in a gel. Upon exposure to ionizing radiation, polymerization proceeds within the gel matrix, thereby changing several measurable physical properties that can then be related quantitatively to absorbed dose. Several previous studies have examined how various nuclear magnetic resonance (NMR) properties, such as the relaxation rates of water protons, change with dose, and magnetic resonance imaging (MRI) has been used successfully to measure three-dimensional dose distributions in irradiated polymer gels. Here we report our first observations of the manner in which the chemical shift of xenon gas (129Xe) dissolved in a gel changes with absorbed dose, and we introduce the potential use of high resolution xenon NMR spectra for understanding better the dose response of gels. 129Xe possesses a large chemical shift range and xenon spectra are sensitive to subtle changes in the physical and chemical environments in which the gas is dissolved. For doses ranging from 0 Gy to 40 Gy we found that the mean chemical shift of 129Xe was linearly related to dose, and that the gel dosimeter could be described in terms of a two-component model undergoing fast exchange. We found no evidence of radiation damage to the gelatin matrix at doses between 0 Gy and 40 Gy. At 40 Gy, the fast-exchange model begins to break down, and distinct gelatin and poly(methacrylate) resonances are observed at higher doses. High resolution NMR measurements of xenon provide a novel method for probing radiation dose effects in irradiated polymer gels.

Differential anterior prefrontal activation during the recognition stage of a spatial working memory task.

Neuroimaging studies commonly show widespread activations in the prefrontal cortex during various forms of working memory and long-term memory tasks. However, the anterior prefrontal cortex (aPFC, Brodmann area 10) has been mainly associated with retrieval in episodic memory, and its role in working memory is less clear. We conducted an event-related functional magnetic resonance imaging study to examine brain activations in relation to recognition in a spatial delayed-recognition task. Similar to the results from previous findings, several frontal areas were strongly activated during the recognition phase of the task, including the aPFC, the lateral PFC and the anterior cingulate cortex. Although the aPFC was more active during the recognition phase, it was also active during the delay phase of the spatial working memory task. In addition, the aPFC showed greater activity in response to negative probes (non-targets) than to positive probes (targets). While our analyses focused on examining signal changes in the aPFC, other prefrontal regions showed similar effects and none of the areas were more active in response to the positive probes than to the negative probes. Our findings support the conclusion that the aPFC is involved in working memory and particularly in processes that distinguish target and non-target stimuli during recognition.

Tissue localization and regulation by juvenile hormone of human allergen Bla g 4 from the German cockroach, Blattella germanica (L.).

The German cockroach, Blattella germanica (L.), produces several potent protein aeroallergens, including Bla g 4, a approximately 20 kDa lipocalin. RT-PCR, Northern analyses and in situ hybridization showed that Bla g 4 is expressed only in the adult male reproductive system. Western blotting and ELISA with rBla g 4 antiserum detected immunoreactivity in the utricles and the conglobate gland, but not in other tissues of the male reproductive system. The Bla g 4 protein content of males increased from adult emergence to day 14, but during copulation Bla g 4 was depleted in the male and transferred to the female within the spermatophore. Topical application of juvenile hormone III stimulated Bla g 4 production by both conglobate gland and utricles.

Sustained mnemonic response in the human middle frontal gyrus during on-line storage of spatial memoranda.

The mapping of cognitive functions to neural systems is a central goal of cognitive neuroscience. On the basis of homology with lesion and physiological studies in nonhuman primates, Brodmann's area (BA) 46/9 in the middle frontal gyrus (MFG) has been proposed as the cortical focus for both the storage as well as processing components of working memory in the human brain, but the evidence on the segregation of these components and their exact areal localization has been inconsistent. In order to study this issue and increase the temporal resolution of functional mapping, we disambiguated the storage component of working memory from sensory and motor responses by employing functional magnetic resonance imaging (fMRI) in spatial delayed-response (DR) tasks with long delay intervals and different conditions of demand. We here show that BA 46 can support a sustained mnemonic response for as long as 24 sec in a high-demand task and the signal change in this area exceeded that in the other prefrontal areas examined. Our findings support a conservation of functional architecture between human and nonhuman primate in showing that the MFG is prominently engaged in the storage of spatial information.

Functional MR imaging of regional brain activation associated with the affective experience of pain.

OBJECTIVE: Current models propose that the experience of pain includes both sensory and affective components. Our purpose was to use functional MR imaging to determine areas of the brain engaged by the affective dimension of pain. SUBJECTS AND METHODS: Twelve healthy adults underwent functional MR imaging using a gradient-echo echoplanar technique while a cold pressor test, consisting of cold and pain tasks, was applied first to one foot and then to the other. The cold task involved the application of cold water (14-20 degrees C) that was not at a painful level. For the pain task, the water temperature was then lowered to a painful temperature (8-14 degrees C) and subsequently to the pain threshold (3-8 degrees C). Images acquired at room temperature before the cold and pain tasks served as a baseline task. Composite maps of brain activation were generated by comparing the baseline task with the cold task and the cold task with the pain task. The significance of signal changes was estimated by randomization of individual activation maps. RESULTS: Cold-related activation (p < 0.01) was found in the postcentral gyrus bilaterally, laterally, and inferiorly to the primary motor-sensory area of the foot and at a site near the second somatosensory site. Activation also occurred in the frontal lobe (the bilateral middle frontal gyri and the right inferior frontal gyrus), the left anterior insula, the left thalamus, and the superior aspect of the anterior cingulate gyrus (seen at one slice location). Pain-related activation (p < 0.01) included the anterior cingulate gyrus (seen at four slice locations); the superior frontal gyrus, especially on the right; and the right cuneus. CONCLUSION: Compared with the basic sensory processing of pain, the affective dimension of pain activates a cortical network that includes the right superior frontal gyrus, the right cuneus, and a large area of the anterior cingulate gyrus.

Changes in rat cerebral blood volume due to modulation of the 5-HT(1A) receptor measured with susceptibility enhanced contrast MRI.

Brain blood volume changes in the rat in response to 5-HT(1A) agonist and antagonist administration were measured using susceptibility contrast enhanced magnetic resonance imaging (MRI). Administration of the 5-HT(1A) agonist 8-OH-DPAT resulted in decreases in fractional brain blood volumes. Administration of the 5-HT(1A) antagonist WAY-100635 following a dose of 8-OH-DPAT resulted in increases in fractional blood volumes greatest in hippocampus and cortex and smallest in thalamus and caudate-putamen. The magnitude of the regional increases in blood volumes paralleled the distribution of 5-HT(1A) receptors in the rat brain. Administration of WAY-100635 alone resulted in decreases in cortical blood volume and increases in cerebellar blood volume.

The relationship of problems in biomedical MRI to the study of porous media.

The NMR methods that are used to characterize inanimate porous media measure relaxation times and related phenomena and material transport, fluid displacement and flow. Biological tissues are comprised of multiple small, fluid-filled compartments, such as cells, that restrict the movement of the bulk solvent water and whose constituents influence water proton relaxation times via numerous interactions with macromolecular surfaces. Several of the methods and concepts that have been developed in one field of application are also of great value in the other, and it may be expected that technical developments that have been spurred by biomedical applications of MR imaging will be used in the continuing study of porous media. Some recent specific studies from our laboratory include the development of multiple quantum coherence methods for studies of ordered water in anisotropic macromolecular assemblies, studies of the degree of restriction of water diffusion in cellular systems, multiple selective inversion imaging to depict the ratios of proton pool sizes and rates of magnetization transfer between proton populations, and diffusion tensor imaging to depict tissue anisotropies. These illustrate how approaches to obtain structural information from biological media are also relevant to porous media. For example, the recent development of oscillating gradient spin echo techniques (OGSE), an approach that extends our ability to resolve apparent diffusion changes over different time scales in tissues, has also been used to compute surface to volume measurements in assemblies of pores. Each of the new methods can be adapted to provide spatially resolved quantitative measurements of properties of interest, and these can be efficiently acquired with good accuracy using fast imaging methods such as echo planar imaging. The community of NMR scientists focused on applications to porous media should remain in close communication with those who use MRI to study problems in biomedicine, to their mutual benefits.

Hemispheric dominance of cortical activity evoked by focal electrogustatory stimuli.

Functional magnetic resonance imaging was used to observe cortical hemodynamic responses to electric taste stimuli applied separately to the right and left sides of the tongue tip. In 11 right-handed normal adults activation occurred primarily in the insular cortex, superior temporal lobe, inferior frontal lobe, including premotor regions, and in inferior parts of the postcentral gyrus. Unexpectedly, the location and laterality of activation were largely identical regardless of the side of the tongue stimulated. Activation in the superior insula, the presumed location of primary gustatory cortex, was predominantly, but not exclusively, in the right hemisphere, whereas central (more inferior) insular activations were more evenly bilateral. Right hemispheric dominance of activation also occurred in premotor regions (Brodmann areas 6 and 44), whereas left hemispheric dominance occurred only in the superior temporal cortex (Brodmann areas 22/42). The electric taste-evoked hemodynamic response pattern was more consistent with activation of the gustatory system than activation of somatosensory systems. The results suggest that the sites for cortical processing of electric taste information are dependent on hemispheric specialization.

Regional brain and ventricular volumes in Tourette syndrome.

BACKGROUND: The pathophysiology of Tourette syndrome (TS) is thought to involve disturbances in cortico-striato-thalamo-cortical circuitry. The morphological characteristics of the cortical and associated white matter portions of these circuits have not been previously examined in TS subjects. METHODS: High-resolution anatomical magnetic resonance images were acquired in 155 TS and 131 healthy children and adults. The cerebrums and ventricles were isolated and then parcellated into subregions using standard anatomical landmarks. RESULTS: For analyses that included both children and adults, TS subjects were found to have larger volumes in dorsal prefrontal regions, larger volumes in parieto-occipital regions, and smaller inferior occipital volumes. Significant inverse associations of cerebral volumes with age were seen in TS subjects that were not seen in healthy controls. Sex differences in the parieto-occipital regions of healthy subjects were diminished in the TS group. The age-related findings were most prominent in TS children, whereas the diminished sex differences were most prominent in TS adults. Group differences in regional ventricular volumes were less prominent than in the cerebrum. Regional cerebral volumes were significantly associated with the severity of tic symptoms in orbitofrontal, midtemporal, and parieto-occipital regions. CONCLUSIONS: Broadly distributed cortical systems are involved in the pathophysiology of TS. Developmental processes, sexual dimorphisms, and compensatory responses in these cortical regions may help to modulate the course and severity of tic symptoms.

Mutual information analysis of the EEG in patients with Alzheimer's disease.

OBJECTIVE: Mutual information provides a measure of both the linear and nonlinear statistical dependencies between two time series. Cross-mutual information (CMI) is used to quantify the information transmitted from one time series to another, while auto mutual information (AMI) in a time series estimates how much on average the value of the time series can be predicted from values of the time series at preceding points. The aim of this study is to assess information transmission between different cortical areas in Alzheimer's disease (AD) patients by estimating the average CMI between EEG electrodes. METHODS: We recorded the EEG from 16 scale electrodes in 15 AD patients and 15 age-matched normal controls, and estimated the local, distant, and interhemispheric CMIs of the EEG in both groups. The rate of decrease (with increasing delay) of the AMI of the EEG was also measured to evaluate the complexity of the EEG in AD patients. RESULTS: The local CMI in AD subjects was lower than that in normal controls, especially over frontal and antero-temporal regions. A prominent decrease in information transmission between distant electrodes in the right hemisphere and between corresponding interhemispheric electrodes was detected in the AD patients. In addition, the AMIs throughout the cerebrums of the AD patients decreased significantly more slowly with delay than did the AMIs of normal controls. CONCLUSIONS: These results are consistent with previous findings that suggest the association of EEG abnormalities in AD patients with functional impairment of information transmission in long cortico-cortical connections.

Dysprosium-bearing red cells as potential transverse relaxation agents for MRI.

The cytosol of intact human red blood cells was loaded with 28.1 +/- 3.4 mM of dysprosium DTPA-BMA using a hypoosmotic technique. When loaded cells were diluted with saline and control cells to give an average dysprosium concentration of 3.3 +/- 0.5 mM, the transverse relaxation rate constants R(*)(2) and R(2) increased. R(*)(2) increased from 7.5 +/- 0.9 sec(-1) to 356 +/- 50 sec(-1), and R(2) increased from 7.4 +/- 0.7 sec(-1) to 148 +/- 40 sec(-1). After lysing, R(*)(2) was 6.0 +/- 0.6 sec(-1) in the control and 13.4 +/- 1.5 sec(-1) in the mixture; R(2) was 6.4 +/- 1.1 sec(-1) and 9.8 +/- 2.4 sec(-1), respectively. Thus, the relaxivity effects were enhanced by sequestration of the dysprosium within intact red cells, and this effect was lost after lysis. At a circulating whole-blood concentration of 0.81 +/- 0.15 mM in rats, the liver signal intensity dropped 29.9% +/- 3.7% and kidney signal intensity dropped 19.4% +/- 8.7%. Dysprosium-loaded cells might be useful in the study of perfusion and tissue blood volume.

The functional neural architecture of components of attention in language-processing tasks.

Using functional magnetic resonance imaging we examined three important dimensions of attentional control (selective attention, divided attention, and executive function) in 25 neurologically normal, right-handed men and women, using tasks involving the perception and processing of printed words, spoken words, or both. In the context of language-processing manipulations: selective attention resulted in increased activation at left hemisphere parietal sites as well as at inferior frontal sites, divided attention resulted in additional increases in activation at these same left hemisphere sites and was also uniquely associated with increased activation of homologous sites in the right hemisphere, and executive function (measured during a complex task requiring sequential decision-making) resulted in increased activation at frontal sites relative to all other conditions. Our findings provide support for the belief that specific functional aspects of attentional control in language processing involve widely distributed but distinctive cortical systems, with mechanisms associated with the control of perceptual selectivity involving primarily parietal and inferior frontal sites and executive function engaging specific sites in frontal cortex.

Neonatal auditory activation detected by functional magnetic resonance imaging.

The objective of this study was to detect auditory cortical activation in non-sedated neonates employing functional magnetic resonance imaging (fMRI). Using echo-planar functional brain imaging, subjects were presented with a frequency-modulated pure tone; the BOLD signal response was mapped in 5 mm-thick slices running parallel to the superior temporal gyrus. Twenty healthy neonates (13 term, 7 preterm) at term and 4 adult control subjects. Blood oxygen level-dependent (BOLD) signal in response to auditory stimulus was detected in all 4 adults and in 14 of the 20 neonates. FMRI studies of adult subjects demonstrated increased signal in the superior temporal regions during auditory stimulation. In contrast, signal decreases were detected during auditory stimulation in 9 of 14 newborns with BOLD response. fMRI can be used to detect brain activation with auditory stimulation in human infants.