Searching for a baseline: functional imaging and the resting human brain.

Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.

Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function.

Medial prefrontal cortex (MPFC) is among those brain regions having the highest baseline metabolic activity at rest and one that exhibits decreases from this baseline across a wide variety of goal-directed behaviors in functional imaging studies. This high metabolic rate and this behavior suggest the existence of an organized mode of default brain function, elements of which may be either attenuated or enhanced. Extant data suggest that these MPFC regions may contribute to the neural instantiation of aspects of the multifaceted "self." We explore this important concept by targeting and manipulating elements of MPFC default state activity. In this functional magnetic resonance imaging (fMRI) study, subjects made two judgments, one self-referential, the other not, in response to affectively normed pictures: pleasant vs. unpleasant (an internally cued condition, ICC) and indoors vs. outdoors (an externally cued condition, ECC). The ICC was preferentially associated with activity increases along the dorsal MPFC. These increases were accompanied by decreases in both active task conditions in ventral MPFC. These results support the view that dorsal and ventral MPFC are differentially influenced by attentiondemanding tasks and explicitly self-referential tasks. The presence of self-referential mental activity appears to be associated with increases from the baseline in dorsal MPFC. Reductions in ventral MPFC occurred consistent with the fact that attention-demanding tasks attenuate emotional processing. We posit that both self-referential mental activity and emotional processing represent elements of the default state as represented by activity in MPFC. We suggest that a useful way to explore the neurobiology of the self is to explore the nature of default state activity.

A default mode of brain function.

A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

Emotion-induced changes in human medial prefrontal cortex: I. During cognitive task performance.

Regional cerebral blood flow (BF) was examined in regions of the medial prefrontal cortex (MPFC) with positron-emission tomography while subjects performed two cognitive tasks, reading nouns aloud and generating appropriate verbs for the same nouns. The control task was passive viewing of the same words. BF was reduced in regions of the MPFC during word reading and naive verb generation, relative to a control state in which the subjects passively viewed nouns. Practicing verb generation produced improved performance, as measured by response time, which was strongly correlated with further reductions in MPFC and hypothalamic BF. After practice, when verb generation was performed on a novel list of words, reaction times slowed and the pattern of MPFC BF reverted to that seen in the word reading and naive conditions. A separate behavioral study of the verb-generation task indicated that anxiety, high during naive use-generation as measured by heart rate and self-report, decreased with practice on the task but returned with the introduction of a novel list of words. Taken together, these results suggest that the MPFC is part of a network, including the hypothalamus and brainstem, whose activity reflects a dynamic interplay between cognitive task performance and emotion.

Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety.

Regional cerebral blood flow (BF) was examined in the human medial prefrontal cortex (MPFC) with positron emission tomography during anticipatory anxiety. Transient anxiety was induced in normal subjects by having them anticipate a painful shock to the fingers of one hand. BF was decreased during anticipatory anxiety, relative to an eyes-closed resting condition, in two regions of the MPFC (Brodmann Areas 10/32 and 24/25). BF decreases in these areas were inversely correlated with anxiety self rating, such that the least anxious subjects exhibited the largest BF reductions, whereas the most anxious subjects showed no significant BF reduction or a slight increase. BF changes in MPFC and in the midbrain were correlated with each other and with anxiety self rating. These results are consistent with the hypothesis that BF reductions in MPFC, previously observed in cognitive tasks, reflect a dynamic balance between focused attention and subject anxiety and may occur from a functionally active baseline or default state. The characterization of such relationships within the human brain enables new insights into the integration of cognition and emotion.

The emotional modulation of cognitive processing: an fMRI study.

The functional neuroanatomy of visual processing of surface features of emotionally valenced pictorial stimuli was examined in normal human subjects using functional magnetic resonance imaging (fMRI). Pictorial stimuli were of two types: emotionally negative and neutral pictures. Task performance was slower for the negatively valenced than for the neutral pictures. Significant blood oxygen level dependent (BOLD) increases occurred in the medial and dorsolateral prefrontal cortex, midbrain, substantia innominata, and/or amygdala, and in the posterior cortical visual areas for both stimulus types. Increases were greater for the negatively valenced stimuli. While there was a small but significant BOLD decrease in the subgenual prefrontal cortex, which was larger in response to the negatively valenced pictures, there was an almost complete absence of other decreases prominently seen during the performance of demanding cognitive tasks [Shulman, G. L., Fiez, J. A., Corbetta, M., Buckner, R. L., Miezin, F. M., Raichle, M. E., & Petersen, S. E. (1997). Common blood flow changes across visual tasks: II. Decreases in cerebral cortex. Journal of Cognitive Neuroscience, 9, 648--663]. These results provide evidence that the emotional valence and arousing nature of stimuli used during the performance of an attention-demanding cognitive task are reflected in discernable, quantitative changes in the functional anatomy associated with task performance.

Cerebral venous thrombosis in neonates and children.

Twenty-five patients (10 neonates, 15 children) with cerebral venous thromboses diagnosed by magnetic resonance imaging or computed tomography over a 10-year period were reviewed retrospectively. Two groups were analyzed separately because of their differing modes of presentation and outcome. Eighty percent of neonates presented with seizures and the outcomes were unfavorable in more than 50%. Thrombosis usually was associated with an acute systemic illness, such as shock or dehydration. In comparison, headache was the most common mode of presentation in the older children (excluding infants) and their outcomes generally were favorable. Thrombosis in this group usually occurred in the setting of a hypercoagulable state or an infectious process. In both groups, global or focal neurologic findings on initial examination unrelated to increased intracranial pressure correlated with the presence of an infarction on computed tomography or magnetic resonance imaging. Infants and children with infarction due to a deep venous thrombosis often had persistent neurologic disability at subsequent examination. No sequelae were observed in those children and neonates only with thrombosis or with superficial venous infarction. Treatment for both groups was conservative. No patient was anticoagulated specifically for the thrombosis. The good outcomes in most patients suggest that acute anticoagulation may not be indicated.

Investigation of stroke in sickle cell disease by 1H nuclear magnetic resonance spectroscopy.

Localized proton nuclear magnetic resonance spectroscopy (MRS), obtained with stimulated echo and spin echo sequences, MR imaging (MRI) and MR angiography (MRA) were used to study the brain in 13 children and adolescents with sickle cell disease. Regions of interest (ROI) studied by MRS included regions appearing normal on MRI as well as regions showing complications of sickle cell disease, including focal deep white matter areas of high signal intensity (deep white matter ischemia, DWMI) seen on long TR images, focal atrophic brain areas, and infarcts. The findings in these studies are summarized as follows: Normal-appearing regions on MRI have normal MRS. In ROI including small areas of DWMI, lactate elevation was not detected, but the levels of N-acetyl-aspartate (NAA) appeared slightly elevated. In areas of DWMI 1-2 cm in size, reduced blood flow could be seen on MRA and lactate elevation could be detected with MRS. When blood flow to a DWMI region was normal, NAA was reduced and there was little lactate elevation, as cell death had already occurred. ROI consisting of atrophic tissue had reduced NAA levels but total creatine levels were not changed. Sometimes lipids, presumably from broken cell membrane, could be detected. In regions of past massive stroke, all metabolites were absent except for small amounts of lactate or lipids.

Pediatric magnetic resonance angiography: assessment of stroke.

Thirty-one (59.6%) of 52 magnetic resonance angiographic (MRA) studies performed on pediatric patients were for evaluation of strokes. Thirteen of the 31 patients (41.9%) of MRA studies were positive for either vascular occlusion or congenital vascular malformation (arteriovenous, venous, or aneurysm). Results indicate that MRA is a valuable noninvasive diagnostic tool that can be routinely performed as part of the initial magnetic resonance evaluation, often thereby avoiding the need for conventional angiography in occlusive vascular disease, and permitting the performance of conventional angiography, in the case of vascular malformations, later when the patient is stable.

Pediatric craniocervical spiral CT.

Spiral CT, which consists of rapid volumetric data acquisition and planar image display, was performed on 100 children undergoing examinations of the brain and head and neck for a variety of clinical indications. The technique was evaluated for image quality and impact on clinical practice. Images of the brain were generally of diagnostic quality in infants and young children but not in older children, due to their larger heads and present X-ray tube current limitations. The lower contrast resolution demands in imaging head and neck structures permitted acquisition of high quality images in all age groups. The rapidity of the technique allowed vascular phase imaging with one-sixth to one quarter the amount of contrast medium injected routinely, reduced the number of artifacts related to patient motion and occasionally permitted scanning of young patients without sedation. As a consequence, the spiral technique appears to have the potential for improving the efficiency and safety of diagnostic CT in investigation of the brain, head and neck in children.

Use of computed tomography, magnetic resonance imaging, and localized 1H magnetic resonance spectroscopy in Canavan's disease: a case report.

The neuroradiological evaluation of Canavan's disease in a 38-month-old girl is discussed. Computed tomography showed diffuse symmetrical low attenuation values of the subcortical and deep cerebral white matter. Magnetic resonance imaging demonstrated symmetrical diffuse low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. With the use of 1H magnetic resonance spectroscopy, we were able to show elevated levels of N-acetylaspartic acid in the occipital lobe of our patient. The in vivo measurement of N-acetylaspartic acid in the brain by 1H magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan's disease. With the increasing availability of magnetic resonance spectroscopy, clinicians may be able to confirm the diagnosis of Canavan's disease immediately after magnetic resonance imaging reveals the typical abnormalities of the white matter.

Regional variation in brain lactate in Leigh syndrome by localized 1H magnetic resonance spectroscopy.

Localized water-suppressed 1H magnetic resonance spectroscopy was performed in an 11-month-old infant with Leigh syndrome. Spectra obtained from the basal ganglia, occipital cortex, and brainstem showed elevations in lactate, which were most pronounced in regions where abnormalities were seen with routine T2-weighted magnetic resonance imaging. This approach has allowed us to examine metabolism in brain tissue directly and noninvasively, and may provide a sensitive means for evaluating metabolic disease and the response to therapy in the brain.

Computed tomography versus magnetic resonance imaging. Of the pediatric central nervous system. Techniques, indications, and examples.

The techniques for computed tomography and magnetic resonance imaging are described. Indications are given for the two procedures as well as the rationale for selection of one or the other in evaluation of the pediatric central nervous system. The benefits derived from each one are illustrated by a series of representative reproductions.

MR findings in rhinocerebral mucormycosis.

A case of rhinocerebral mucormycosis evaluated by magnetic resonance (MR) imaging is presented, with inflammatory changes in the paranasal sinuses and orbit. Extension of the infection into the cavernous sinus, with cavernous sinus thrombosis and internal carotid artery narrowing, was well demonstrated on pre- and postgadolinium MR images. Infarctions in the anterior choroidal artery distribution suggested intracranial invasion of basal arteries, and watershed distribution infarctions attested to the tenuousness of flow through a narrowed cavernous carotid artery. Magnetic resonance effectively demonstrated the wide array of findings possible in rhinoorbitocerebral mucormycosis.

Sonography of the internal capsule and basal ganglia in infants. Part II. Localization of pathologic processes in the sagittal section through the caudothalamic groove.

Sagittal sonograms through the caudothalamic groove routinely display a gangliothalamic ovoid delimited by the lateral ventricle, the perimesencephalic cistern, and the radiations of the corpus callosum. The caudothalamic groove divides the superior surface of the ovoid into an anterior caudate arc and a posterior thalamic arc. The cerebral peduncle divides the inferior surface of the ovoid into an anterior ganglial arc, a middle peduncular arc, and a posterior thalamic arc. The genu of internal capsule constantly courses from the anterior end of the caudothalamic groove down to the peduncular arc and is easily identified. The gangliothalamic ovoid exhibits four obliquely oriented bands of increased and decreased echogenicity. The anteriormost hyperechoic band 1 corresponds to the head of the caudate nucleus. Hypoechoic band 2 corresponds to the globus pallidus, genu of the internal capsule, and cerebral peduncle. Hyperechoic band 3 corresponds to the ventral and lateral thalamic nuclei (exclusive of the pulvinar). Hypoechoic band 4 corresponds to the pulvinar. Lesions of the medial nucleus of the globus pallidus appear as hyperechoic foci that abut on the anterior surface of genu just above the peduncle and that have a narrow convex caudal margin. Lesions of the lateral nucleus of globus pallidus abut on the genu distant from the peduncle, spare the medial nucleus adjacent to the peduncle, and have a broad caudal border. Lesions of the head of caudate nucleus affect the anterior pole of the ovoid; those of the body affect the caudate arc superior to the caudothalamic groove. Thalamic lesions increase the echogenicity of bands 3 and 4.

Sonography of the normal neonatal head. Supratentorial structures: state-of-the-art imaging.

Advances in ultrasound equipment now permit display of anatomic structures not previously shown. Correlation of sonograms obtained in vivo with gross and myelin-stained sections of human autopsy material facilitates understanding of these new images.

Ultrasonic anatomy of the normal neonatal and infant spine: correlation with cryomicrotome sections and CT.

High resolution computed neurosonography now displays the details of the spinal canal, subarachnoid space, spinal cord and some emerging nerve roots in axial and sagittal planes. Those familiar with this anatomy may use sonography to detect spinal pathology.

Sonography of the internal capsule and basal ganglia in infants: 1. Coronal sections.

Coronal sonograms in infants obtained with 3.5 and 5.0 MHz sector and linear-array transducers now depict the anterior limb, genu, posterior limb, and sublenticular parts of internal capsule; the caudate nucleus; the putamen; the lateral and medial nuclei of globus pallidus; the lateral and medial medullary laminae of the lenticular nucleus; the nucleus accumbens septi; and some of the thalamic nuclei. Correlation of sonograms obtained in vivo with gross and myelin-stained sections of human brain illustrates the configurations of these structures and the interrelations among them. Physicians familiar with this anatomy may now use sonography to localize focal lesions more accurately than has been possible previously.