Activation by attention of the human reticular formation and thalamic intralaminar nuclei.

It has been known for over 45 years that electrical stimulation of the midbrain reticular formation and of the thalamic intralaminar nuclei of the brain alerts animals. However, lesions of these sectors fail to impair arousal and vigilance in some cases, making the role of the ascending activating reticular system controversial. Here, a positron emission tomographic study showed activation of the midbrain reticular formation and of thalamic intralaminar nuclei when human participants went from a relaxed awake state to an attention-demanding reaction-time task. These results confirm the role of these areas of the brain and brainstem in arousal and vigilance.

Hierarchical processing of tactile shape in the human brain.

It is not known exactly which cortical areas compute somatosensory representations of shape. This was investigated using positron emission tomography and cytoarchitectonic mapping. Volunteers discriminated shapes by passive or active touch, brush velocity, edge length, curvature, and roughness. Discrimination of shape by active touch, as opposed to passive touch, activated the right anterior lobe of cerebellum only. Areas 3b and 1 were activated by all stimuli. Area 2 was activated with preference for surface curvature changes and shape stimuli. The anterior part of the supramarginal gyrus (ASM) and the cortex lining the intraparietal sulcus (IPA) were activated by active and passive shape discrimination, but not by other mechanical stimuli. We suggest, based on these findings, that somatosensory representations of shape are computed by areas 3b, 1, 2, IPA, and ASM in this hierarchical fashion.

Brain atlases--a new research tool.

Conventional brain atlases are collections of micrographs or schematic drawings of brain sections from one or a few brains in which anatomical structures are identified, for example, nuclei, cortical areas and fibre tracts. Conventional brain maps have now been replaced with modern computer-based brain atlases. The structures in computerized atlases are deformable so as to fit the sizes and shapes of individual brains, and transform three-dimensional reconstructions or images of brains into a standard brain format. In order to make generalizations about localization of function and structure at both the macroscopical and microscopical level computerized brain atlases are needed. Computerized brain atlases are also used to compensate for the shrinkage and distortions during sectioning and embedding of post-mortem brains, to study structural-functional relationships in the human brain at both the macroscopical and microscopical level, and variations in gross morphology and microstructure of the human brain, and for establishing a three-dimensional human-brain database for all of the above and also for topographically defined data from the literature.

Visual imagery and visual representation.

Among many controversies in visual neuroscience is whether visual imagery of objects, scenes and living beings is based upon contributions of the early visual areas or depends on hierarchical higher visual areas only, and whether the cortical areas subserving visual imagery are identical to those underlying visual perception. These questions are important for furthering our understanding of vision, since areas active in visual imagery might tell us how the visual cortex represents objects, scenes and living beings. Here, P.E. Roland and B. Gulyás present their hypothesis, based on experimental evidence in man and primates, that the visual areas subserving visual imagery are parieto-occipital and temporo-occipital visual association areas, and that these areas form only a subset of the visual areas engaged in perception. This hypothesis is consistent with the view that objects, scenes and living beings are represented, stored and re-evoked outside the domain of the primary visual cortex and its immediate neighbours.

Functions and structures of the motor cortices in humans.

Humans and non-human primates have several motor areas. Exactly how many is a matter of current debate. A proper parcellation of motor areas must be based on correlated structural and functional differences. Recent studies indicate that the primary motor cortex may be, in reality, two areas (4a and 4p). Similarly, there are undoubtedly two or more cingulate motor areas and perhaps two supplementary motor areas. The homologies between human and monkey brains are striking in some cases, making monkey models of human motor cortices attractive. The doctrine of a strict 'homuncular' somatotopical organization of motor areas will have to be abandoned. The engagement of motor areas in different types of voluntary seems merely a matter of degree of activation rather than exclusive specific contributions.

Illusory arm movements activate cortical motor areas: a positron emission tomography study.

Vibration at approximately 70 Hz on the biceps tendon elicits a vivid illusory arm extension. Nobody has examined which areas in the brain are activated when subjects perceive this kinesthetic illusion. The illusion was hypothesized to originate from activations of somatosensory areas normally engaged in kinesthesia. The locations of the microstructurally defined cytoarchitectonic areas of the primary motor (4a and 4p) and primary somatosensory cortex (3a, 3b, and 1) were obtained from population maps of these areas in standard anatomical format. The regional cerebral blood flow (rCBF) was measured with (15)O-butanol and positron emission tomography in nine subjects. The left biceps tendon was vibrated at 10 Hz (LOW), at 70 or 80 Hz (ILLUSION), or at 220 or 240 Hz (HIGH). A REST condition with eyes closed was included in addition. Only the 70 and 80 Hz vibrations elicited strong illusory arm extensions in all subjects without any electromyographic activity in the arm muscles. When the rCBF of the ILLUSION condition was contrasted to the LOW and HIGH conditions, we found two clusters of activations, one in the supplementary motor area (SMA) extending into the caudal cingulate motor area (CMAc) and the other in area 4a extending into the dorsal premotor cortex (PMd) and area 4p. When LOW, HIGH, and ILLUSION were contrasted to REST, giving the main effect of vibration, areas 4p, 3b, and 1, the frontal and parietal operculum, and the insular cortex were activated. Thus, with the exception of area 4p, the effects of vibration and illusion were associated with disparate cortical areas. This indicates that the SMA, CMAc, PMd, and area 4a were activated associated with the kinesthetic illusion. Thus, against our expectations, motor areas rather than somatosensory areas seem to convey the illusion of limb movement.

Object shape differences reflected by somatosensory cortical activation.

Humans can easily by touch discriminate fine details of the shapes of objects. The computation of representations and the representations of objects differing in shape are, when the differences are not founded in different sensory cues or the objects belong to different categories, assumed to take place in a series of cortical areas, which only show differences at the single-neuron level. How the somatosensory cortex computes shape is unknown, but theoretically it should depend heavily on the curvatures of the object surfaces. We measured regional cerebral blood flow (rCBF) of normal volunteers with positron emission tomography (PET) as an index of neuronal activation. One group discriminated a round set of ellipsoids having a narrow spectrum of curvatures and an oblong set of ellipsoids having a broad spectrum of curvatures. Another group discriminated curvatures. When the rCBF from the conditions round and oblong ellipsoid discrimination was contrasted, part of the cortex lining the postcentral sulcus had significantly higher rCBF when ellipsoids having a broader spectrum of curvatures were discriminated. This cortex was also activated by curvature discrimination. The activation is therefore regarded as crucial for the computation of curvature and in accordance with curvature being a major determinant of object form; this cortex is also crucially active in somatosensory shape perception. A comparison of the activation with cytoarchitectural maps, in the anatomical format of the standard brain for both PET and cytoarchitectural brain images, revealed that this part of the cortex lining the postcentral sulcus is situated caudally from cytoarchitectural area 1 and may involve presumptive area 2 on the posterior bank of the sulcus.

The effect of the GABA-A agonist THIP on regional cortical blood flow in humans. A new test of hemispheric dominance.

We studied the effect of a gamma-aminobutyric acid (GABA)-A receptor-induced postsynaptic inhibition on regional CBF (rCBF) in awake humans. For this purpose we used a new specific GABA-A agonist, 4,5,6,7-tetrahydroisoxazolo(5,4)-pyridin-3-ol (THIP). As part of a new diagnostic procedure for the determination of which hemisphere subserved language, THIP was infused into the internal carotid artery 20 s before measurement of the rCBF. Administered by this route the THIP is distributed to the neocortex and neostriatum. THIP induced a dosage-dependent decrease of the rCBF. The rCBF decrease was not due to any direct effect on the cerebral vessels. The efficiency of the THIP-induced postsynaptic inhibition was tested by having the subjects voluntarily activate the inhibited cortex. During submaximal inhibition the subjects were able voluntarily to counteract decreases of rCBF in superior frontal cortex and motor cortex. Larger doses of THIP abolished this response and depressed the rCBF to baseline levels (20 ml/100 g/min). This was associated with 10-min total depression of function of the anterior two-thirds of the injected hemisphere. An analysis of the changes of rCBF in activated and nonactivated cortex--with and without THIP-induced inhibition--showed that it would be very unlikely that average increases in synaptic inhibition would increase rCBF in neocortical areas. Intracarotid injection of the water-soluble, nonirritative THIP is a very useful alternative to sodium amytal injection for determination of hemispheric dominance.

Direct comparison of single-scan autoradiographic with multiple-scan least-squares fitting approaches to PET CMRO2 estimation.

The time course of local cerebral radioactivity concentration after bolus inhalation of oxygen gas labeled with O-15 was measured in a rapid dynamic sequence of positron tomographic images. Four normal subjects were studied at rest. In each study, 15 multiple-slice image sets were acquired over a 3-min period in a Scanditronix model 384 tomograph. The radioactivity concentration in arterial blood was measured at 1-s intervals by means of a pump-fed flow-through detector. Pump effluent was directed to discrete samples that were separated into plasma and cell fractions to estimate the accumulation of labeled, recirculating water arising from systemic metabolism. Stereotactically matched scans of local cerebral blood flow and volume were acquired in the same imaging session, and the derived values were used as fixed parameters in the model fits of the time courses of pixel radioactivity in the oxygen study. Rapid nonlinear least-squares parameter optimization was used to estimate simultaneously the local CMRO2 and the brain/blood relative distribution volume for water in each image pixel. The same scan data were combined into effective single frames of various starting times and durations for analysis using the single-scan ("autoradiographic") approach to CMRO2 estimation, which requires a presumed value for relative distribution volume. Oxygen use values derived using this approach were observed to be strongly dependent on the relative distribution volume value chosen, particularly for long study durations. However, for each gray matter region of interest studied, a uniform value for the relative distribution volume existed such that the estimated CMRO2 values were independent of the starting time and duration of the single scan used, and were furthermore the same as that yielded by the multiple-scan least-squares fitting of the total time course in the same region. We conclude that the properties of the single-scan and multiple-scan approaches are very similar at the same total study duration, provided that the value selected for the water relative distribution volume brings the measured and computed tissue time courses into correspondence.

Accuracy and precision of the computerized brain atlas programme for localization and quantification in positron emission tomography.

The computerized brain atlas programme (CBA) provides a powerful tool for the anatomical analysis of functional images obtained with positron emission tomography (PET). With a repertoire of simple transformations, the data base of the CBA is first adapted to the anatomy of the subject's brain represented as a set of magnetic resonance (MR) or computed tomography (CT) images. After this, it is possible to spatially standardize (reformat) any set of tomographic images related to the subject, PET images, as well as CT and MR images, by applying the inverse atlas transformations. From these reformatted images, statistical images, such as average images and associated error images corresponding to different groups of subjects, may be produced. In all these images, anatomical structures can be localized using the atlas data base and the functional values can be evaluated quantitatively. The purpose of this study was to determine the spatial and quantitative accuracy and precision of the calculated regional mean values. Therefore, the CBA was applied to regional CBF (rCBF) measurements with [11C]fluoromethane and PET on 26 healthy male volunteers during rest and during three different physiological stimulation tasks. First, the spatial accuracy and precision of the reformation process were determined by measuring the spread of defined anatomical structures in the reformatted MR images of the subjects. Second, the mean global CBF and the mean rCBF in the average PET images were compared with the global CBF and rCBF in the original PET images. Our results demonstrate that the reformation process accurately transformed the individual brains of the subjects into the standard brain anatomy of the CBA. The precision of the reformation process had an SD of approximately 1 mm for the lateral dislocation of midline structures and approximately 2-3 mm for the dislocation of the inner and outer brain surfaces. The quantitative rCBF values of the original PET images were accurately represented in the reformatted PET images. Moreover, this study shows that the application of the CBA improves the analysis of functional PET images: (a) The average PET images had a low background noise [0.4 ml/100 g/min +/- 0.7 (SD)] compared to the mean rCBF changes specifically induced by physiological stimulation. (b) The reformatted PET images had a voxel volume of 10.9 mm3. Owing to this high sampling resolution, it was possible to differentiate the mean rCBF changes in adjacent activated fields such as the left motor hand area from the sensory hand area and the left premotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Positron emission tomographic measurements of cerebral glucose utilization using [1-11C]D-glucose.

Regional CMRglc was measured in seven healthy volunteers with positron emission tomography using [1-11C]D-glucose. Regional CBF was measured using [11C]fluoromethane. The arteriovenous differences of unlabeled glucose and oxygen together with 11C metabolites were also measured. In addition to the loss of [11C]CO2, a loss of acidic 11C metabolites was also detected. A three-compartment model was applied to the tracer data in the time interval 0-24 min. After correction for the loss of 11C metabolites, the tracer method gave an average CMRglc of 26.4 +/- 1.9 (SD) mumol/100 g/min, close to the value obtained with the Fick principle. After correction for the loss of [11C]CO2 only, the tracer method gave 23.6 +/- 2.1 mumol/100 g/min, compatible with (1/6) CMRO2, obtained with the Fick principle. These results and the time course of the loss of acidic 11C metabolites are consistent with the presence of nonoxidative metabolism of glucose that causes an early loss of mainly [11C]lactate after a bolus injection of the tracer. This implies that [1-11C]D-glucose measures the rate of glucose oxidation rather than the total CMRglc. The experiments using [1-11C]D-glucose were compared to five analogous experiments using [U-11C]D-glucose together with [15O]H2O as a flow tracer. After correction for the loss of [11C]CO2, the two glucose tracers gave similar global values of CMRglc and other parameters associated with glucose utilization, but with labeling in the carbon-1 position, the loss of [11C]CO2 was substantially delayed and the contrast between gray and white matter was improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Astereognosis. Tactile discrimination after localized hemispheric lesions in man.

The specific object of this study was to determine which cortical areas have to be damaged or disconnected to cause an impairment of somatosensory discrimination (astereognosis). Ninety-three patients with verified unilateral and circumscribed lesions took part in a somatosensory two-alternative forced-choice discrimination of size and shape. The results failed to support earlier views of astereognosis. Only direct damage to or an undercutting of the anterior part of the middle third of the postcentral gyrus caused impairment of size and shape discrimination (astereognosis) contralateral to the lesion. When the hand is used for stereognostic discrimination, the integration of somatosensory impulse patterns into spatial information about the objects is believed to take place in the contralateral somatosensory hand area.

Vibratory thresholds in the hands: comparison of patients with suprathalamic lesions with normal subjects.

Absolute thresholds for sensation of a 100-Hz mechanical sine-wave stimulus applied with an electromagnetic vibrator were measured on eight stimulus points in the glabrous skin of the human hand in normal subjects and in patients with verified, circumscribed unilateral suprathalamic lesions of the hemispheres. In both groups, the threshold on the hypothenar eminence was lower than the threshold on the third digit, which in turn had a lower threshold than the fifth digit. For each locus of stimulation, there was a rectilinear regression of threshold with age. Women had lower thresholds than men. The spatial distribution of the thresholds might suggest that Pacinian corpuscles are the receptors activated by threshold stimulation. Unilateral suprathalamic lesions of the hemisphere did not cause any elevation of vibratory thresholds.

Interference between two concurrent tasks is associated with activation of overlapping fields in the cortex.

Interference between two concurrent tasks can be measured as an increased reaction time during simultaneous performance compared to when each task is performed alone. We tested the hypothesis that two tasks interfere because they require activation of overlapping areas of the cerebral cortex. With positron emission tomography we measured cortical activation as fields with significant increase in regional cerebral blood flow during single task performance of an auditory and a visual go/no-go task and an auditory and a visual short-term memory (STM) task. In a separate experiment we measured the degree of interference between the two go/no-go tasks and between the two STM tasks during dual task performance. Both the two go/no-go tasks and the two STM tasks activated overlapping parts of the cortex and interfered significantly during dual task performance. The two STM tasks had a larger volume of overlap and also significantly larger increase in reaction time during dual task performance, compared to the go/no-go tasks. The results thus indicate that two concurrent tasks interfere, with a resulting increase in reaction time, if they require activation of overlapping parts of the cortex.

Cortical fields participating in form and colour discrimination in the human brain.

In order to map the anatomical structures participating in the analysis and processing of visual information related to discrimination of form and colour, we measured with positron emission tomography (PET) regional cerebral blood flow (rCBF) as an indicator of metabolic activity in ten right-handed volunteers during visual discrimination tasks, namely reference, form and colour tasks. Form discrimination specifically increased rCBF bilaterally in the inferior temporal and cingulate gyri, and in the left superior temporal, left occipital lateral, and left angular gyri, whereas colour discrimination did so in the left occipital superior and lateral, left parahippocampal, left occipito-temporal medial (lingual), and left superior parietal gyri, and the right precuneus.

Cortical representation of self-paced finger movement.

We compared the cortical fields activated by simple, self-paced index-finger flexions with those activated during visually triggered movement and rest using PET. Of 12 fields detected during self-paced movement compared to rest, three were located in the classically defined motor areas: primary motor area (M1), premotor cortex (PM) and supplementary motor area (SMA). The latter extended into the cingulate motor area (CMA). Four corresponding clusters were also found when triggered movement was subtracted from self-paced movement. The change in regional cerebral blood flow (rCBF) was greater in SMA than in PM during self-paced movement compared with either control. We conclude that repetitive, self-paced index-finger flexions can activate SMA, PM and CMA, and that this movement activates SMA more strongly than PM.

The human entorhinal cortex participates in associative memory.

Animal studies have shown that lesions of the parahippocampal cortex impair learning of visual stimulus-stimulus associations. We tested the hypothesis that recall of paired associates, in contrast to recall of non-associated items, activates the parahippocampal cortex in humans. Ten volunteers had their regional cerebral blood flow measured with positron emission tomography during non-associative recall, and during two conditions with associative recall of visual stimuli. Compared with non-associative recall, associative recall specifically increased the blood flow in a field located in the entorhinal cortex, extending into the presubiculum. Our results demonstrate functional differences between the human hippocampal and parahippocampal cortex, and show that the entorhinal cortex is engaged in associative memory.

Preparation for reaching: a PET study of the participating structures in the human brain.

The regional cerebral blood flow (rCBF) was measured as an indicator of regional metabolic activity with positron emission tomography (PET) in eight subjects who, after seeing a screen with seven targets prepared themselves with their eyes closed to reach these targets. The preparation phase was associated with increases of rCBF in the prefrontal cortex, several remote visual association areas in the parietal lobe, the supramarginal gyrus, the ventrolateral thalamus and the cerebellar vermis. During the course of learning the activations in the parietal visual areas, the supramarginal gyrus and the prefrontal cortex prevailed as a sign of the visual spatial information; its transformation being kept in working memory. The other activations vanished. No activations were seen in the motor cortices, indicating that reaching is a task which does not require substantial preparatory activity of motor cortices prior to the go signal.

Somatosensory areas in man activated by moving stimuli: cytoarchitectonic mapping and PET.

This study was performed to identify neuronal populations in the somatosensory areas engaged in discrimination of moving stimuli on the skin. Changes in regional cerebral blood flow (rCBF) were measured with positron emission tomography (PET) and correlated with cytoarchitectonic sensorimotor areas 4a, 4p, 3a, 3b, and 1. Volunteers discriminated differences in the speed of a rotating brush stimulating the palmar surface. Discrimination of moving stimuli, contrasted to rest, increased the rCBF mainly in primary somatosensory (SI) area 1, but also in area 3b. The parietal operculum (PO) was activated bilaterally. We conclude that area 1 is the area in SI which is mainly responding to discrimination of moving stimuli and that the PO contains several regions engaged in the discrimination of fast transient stimuli.

Activity in motor areas while remembering action events.

Episodic memory for simple commands is better following enacted than verbal encoding. This has been proposed to be due to the possibility to base retrieval on motor information. Here we used PET to test the hypothesis that motor brain areas show increased retrieval-related activity following enacted compared to verbal encoding. Brain activity was also monitored during retrieval after imaginary enactment during encoding. It was found that activity in the right motor cortex was maximal following encoding enactment, intermediate following imaginary encoding enactment, and lowest following verbal encoding. These findings provide support that one basis for the facilitating effect on memory performance of overt, and to a lesser degree covert, encoding enactment is the possibility to base retrieval on motor information.