Altered hemispheric functional dominance during word generation in negative schizophrenia.

Functional brain imaging studies have reported decreased frontal activations in schizophrenia, but hemispheric dominance for language has rarely been assessed. To investigate regional activation and lateralization during word production, we determined normalized regional cerebral blood flow (rCBF) variations with positron emission tomography (PET) and H2(15)O (water labeled with the isotope oxygen 15) in 14 negative schizophrenia patients and 14 volunteers. Subjects were scanned during two trials of three conditions: rest, vocalized verbal fluency, and spontaneous word production. Images were analyzed using an anatomical volumes of interest method, and the two groups' changes were compared, using rest as a baseline. Differences in the lateralization of changes were detected in homologous frontal and inferior parietal regions. The lateralization effects in patients arose from lower activations in the left frontal regions, abnormal right inferior frontal activations, and weaker right inferior parietal deactivation, during the word production tasks. The right hemisphere changes correlated negatively with the performance in verbal fluency. Thus in negative schizophrenia patients, while the activations were less focused on the left hemisphere regions usually engaged in word generation, rCBF changes in the right hemisphere might reflect a compensatory functional pattern.

PET study of the human foveal fixation system.

Positron emission tomography (PET) was used to investigate the functional anatomy of the foveal fixation system in 10 subjects scanned under three different conditions: at rest (REST), during the fixation of a central point (FIX), and while fixating the same foveal target during the presentation of peripheral visual distractors (DIS). Compared with the REST condition, both FIX and DIS tasks activated a common set of cortical areas. First, in addition to the involvement of the occipital visual cortex, both the frontal eye field (FEF) and the intraparietal sulcus (IPS) were bilaterally activated. Right frontal activation was also found in the dorsolateral prefrontal cortex, the inferior part of the precentral gyrus, and the inferior frontal gyrus. These results suggest that both FEF and IPS may constitute the main cortical regions subserving bilaterally the foveal fixation system in humans. The remaining right frontal activations may be considered as part of the anterior attentional network, supporting a role for the right frontal lobe in the allocation of the attentional mechanisms. Compared with the FIX condition, the DIS task also revealed the perceptual and cognitive processes related to the presence of peripheral visual distractors during foveal fixation. In addition to a bilateral activation of the V5/MT motion-sensitive area, a right FEF-IPS network was activated which may correspond to the engagement of the visuospatial attention. Finally, normalized regional cerebral blood flow (NrCBF) decreases were also observed during both DIS and FIX condition performance. Such NrCBF decreases were centered in the superior and middle temporal gyri, the prefrontal cortex, and the precuneus and the posterior retrosplenial part of the cingulate gyrus.

Reopening the mental imagery debate: lessons from functional anatomy.

Over the past few years, the neural bases of mental imagery have been both a topic of intense debate and a domain of extensive investigations using either PET or fMRI that have provided new insights into the cortical anatomy of this cognitive function. Several studies have in fact demonstrated that there exist types of mental imagery that do not rely on primary/early visual areas, whereas a consensus now exists on the validity of the dorsal/ventral-route model in the imagery domain. More importantly, these studies have provided evidence that, in addition to higher order visual areas, mental imagery shares common brain areas with other major cognitive functions, such as language, memory, and movement, depending on the nature of the imagery task. This body of recent results indicates that there is no unique mental imagery cortical network; rather, it reflects the high degree of interaction between mental imagery and other cognitive functions.

Functional anatomy of dominance for speech comprehension in left handers vs right handers.

In order to study the functional anatomy of hemispheric dominance for language comprehension we compared the patterns of activations and deactivations with PET and H(2)15O during a story-listening task in two groups of normal volunteers selected on the basis of their handedness. The reference task was a silent rest. The results showed asymmetrical temporal activations favoring the left hemisphere in right handers (RH) together with Broca's area and medial frontal activations. A rightward lateralization of deactivations located in the parietal and inferior temporal gyrus was also observed. In left handers (LH) the temporal activations were more symmetrical as were the parietal and inferior frontal deactivations. Broca's area and medial frontal gyrus activations were present in LH. The direct comparison of RH and LH activations revealed larger activations in the left superior temporal, in particular in the left planum temporale and temporal pole of RH, while LH activated an additional right middle temporal region. Individual analysis of LH differences images superimposed on individual MRI planes demonstrated an important variability of functional dominance, with two LH leftward lateralized, two symmetrical, and one showing a rightward lateralization of temporal activations. There was no relationship between functional dominance and handedness scores. These results are in accordance with data from aphasiology that suggest a greater participation of the right hemisphere in language processing in LH. In addition, the presence of bilateral deactivations of the dorsal route could support the assumption that LH ambilaterality concerns, in addition to language, other cognitive functions such as visuospatial processing.

Anatomical congruence of metabolic and electromagnetic activation signals during a self-paced motor task: a combined PET-MEG study.

We have investigated the degree of spatial correlation between the cerebral blood flow variations measured by positron emission tomography (PET) and the electromagnetic sources as measured by magnetoencephalography (MEG) in five subjects while performing a self-paced right index finger tapping task. Data were processed independently for each technique using both single-case and intersubject analysis. PET and MEG were coregistered with anatomical magnetic resonance images for each subject. Both extension and flexion motor-related fields were extracted from the MEG signal. Using the single dipole model we identified the motor evoked field 1 (MEF1) in all subjects and the motor field (MF) in three subjects. Individual and intersubject averaged PET data showed consistent contralateral primary sensorimotor (PSM) hand area and bilateral supplementary motor area activation. MEG individual and intersubject averaged results demonstrated that both MEF1 and MF dipoles were localized within the PSM PET activated area. Individual PSM mass center to dipole distance was 12 and 15.3 mm on average for the MEF1 and the MF component, respectively. For the same components, the intersubject averaged analysis shows distances between the PET Z-score maximum and the dipole locations of 6.3 and 15.0 mm, respectively. These results show that PET and MEG MEF1 activation signals spatially coincide within instrumental, registration, and modeling errors.

Cortical anatomy of mental imagery of concrete nouns based on their dictionary definition.

The functional anatomy of the interactions between spoken language and visual mental imagery was investigated with PET in eight normal volunteers during a series of three conditions: listening to concrete word definitions and generating their mental images (CONC), listening to abstract word definitions (ABST) and silent REST. The CONC task specifically elicited activations of the bilateral inferior temporal gyri, of the left premotor and left prefrontal regions, while activations in the bilateral superior temporal gyri were smaller than during the ABST task, during which an additional activation of the anterior part of the right middle temporal gyrus was observed. No activation of the occipital areas was observed during the CONC task when compared either to the REST or to the ABST task. The present study demonstrates that a network including part of the bilateral ventral stream and the frontal working memory areas is recruited when mental imagery of concrete words is performed on the basis of continuous spoken language.

Left planum temporale surface correlates with functional dominance during story listening.

The relationship between anatomical asymmetry of the planum temporale (PT) and functional lateralization for language comprehension was studied in 14 normal volunteers, including five left-handers (LH). PT surfaces and asymmetry were measured in each subject using structural MRI, while functional lateralization was assessed on individual regional cerebral blood flow (rCBF) difference images of a PET-H2(15)O activation protocol in which a story listening condition was contrasted with a control state. Significant positive correlations were found between the left PT surface and the amount of NrCBF increase during the story listening in the left superior temporal gyrus as well as with the left-right activation index in the superior temporal and the temporal pole. Functional imaging data were correlated neither with the right PT surface nor with the right-left PT surface asymmetry index. However the latter index was correlated with handedness scores. The present results indicate that the size of the left PT is the relevant anatomical landmark for language dominance, and demonstrate that anatomical asymmetries are part of the functional variability for language.

Mental navigation along memorized routes activates the hippocampus, precuneus, and insula.

Positron emission tomography was used to investigate the functional anatomy of mental simulation of routes (MSR) in five normal volunteers. Normalized regional cerebral blood flow was measured while subjects mentally navigated between landmarks of a route which had been previously learned by actual navigation. This task was contrasted with both static visual imagery of landmarks (VIL) and silent Rest. MSR appears to be subserved by two distinct networks: a non-specific memory network including the posterior and middle parts of the hippocampal regions, the dorsolateral prefrontal cortex and the posterior cingulum, and a specific mental navigation network, comprising the left precuneus, insula and medial part of the hippocampal regions.

Functional anatomy of human auditory attention studied with PET.

Positron emission tomography was used to investigate the functional anatomy of selective auditory attention in 17 right-handed male volunteers who submitted to different tasks: silent rest (REST) listening to frequent low- or rare high-pitched tones (LIS) delivered randomly to the right or the left ear, selective auditory attention where subjects had to attend to deviants in one ear, right (ATTR) or left (ATTL). Six subjects had the series REST, LIS, ATTR twice, eight subjects the series REST, LIS, ATTL, and the last three subjects the sereis REST, ATTR, ATTL. Event-related potentials were simultaneously recorded with PET and showed significant task and electrode site effects on the N100 amplitude. When compared to REST, LIS elicited bilateral temporal activations of the Heschl's gyri and the planum temporale, with a significant rightward asymmetry, and of the posterior part of the superior temporal gyrus. Significant right precentral and anterior cingulate gyri normalized regional cerebral blood flow increases were observed in the frontal lobe. Both the ATTR and the ATTL conditions, compared to LIS, activated the supplementary motor area, bilateral precentral, and left postcentral cortices without any temporal cortex activation. In addition, the ATTL condition resulted in a right prefrontal cortex activation. Pooling the 14 subjects revealed an asymmetry in the superior temporal gyrus favoring the cortex contralateral to the attended ear. Two major networks seem thus to be involved during selective auditory attention: (1) a local temporal network, on which selective attention produces a modulation of the functional lateralization, and (2) a frontal network that could mediate the temporal cortex modulation by attention.

Use of anatomical parcellation to catalog and study structure-function relationships in the human brain.

We describe a functional neuroanatomy approach that combines structural (MRI) and functional (PET) data at the individual level. For each subject MRI dataset, sulci are first localized using hemisphere surface rendering and sections and stored. Using these landmarks, the subject brain volume is then divided in 100 anatomical volumes of interest (AVOI). AVOI morphometric measurements are readily obtained as well as functional parameters (CBF) after MRI-PET alignment. This approach allows structure-function relationship investigations both at the single case and at the intersubject average level; in addition, individual morphometric and functional parameters can be easily archived in a database for further meta-analysis. This approach is applicable to all imaging modalities and is especially suited for a priori hypothesis testing and for the investigation of interindividual functional neuroanatomy variability.

Cerebral activations during number multiplication and comparison: a PET study.

Positron emission tomography was used to examine the cerebral networks underlying number comparison and multiplication in eight normal volunteers. Cerebral blood flow was measured within anatomical regions of interest defined in each subject using magnetic resonance imaging. Three conditions were used: rest with eyes closed, mental multiplication of pairs of arabic digits and larger-smaller comparison of the same pairs. Both multiplication and comparison activated the left and right lateral occipital cortices, the left precentral gyrus, and the supplementary motor area. Beyond these common activations, multiplication activated also the left and right inferior parietal gyri, the left fusiform and lingual gyri, and the right cuneus. Relative to comparison, multiplication also yielded superior activity in the left lenticular nucleus and in Brodmann's area 8, and induced a hemispheric asymmetry in the activation of the precentral and inferior frontal gyri. Conversely, relative to multiplication, comparison yielded superior activity in the right superior temporal gyrus, the left and right middle temporal gyri, the right superior frontal gyrus, and the right inferior frontal gyrus. These results underline the role of bilateral inferior parietal regions in number processing and suggest that multiplication and comparison may rest on partially distinct networks.

Functional anatomy of spatial mental imagery generated from verbal instructions.

Positron emission tomography (PET) was used to monitor regional cerebral blood flow variations while subjects were constructing mental images of objects made of three-dimensional cube assemblies from auditorily presented instructions. This spatial mental imagery task was contrasted with both passive listening (LIST) of phonetically matched nonspatial word lists and a silent rest (REST) condition. All three tasks were performed in total darkness. Mental construction (CONS) specifically activated a bilateral occipitoparietal-frontal network, including the superior occipital cortex, the inferior parietal cortex, and the premotor cortex. The right inferior temporal cortex also was activated specifically during this condition, and no activation of the primary visual areas was observed. Bilateral superior and middle temporal cortex activations were common to CONS and LIST tasks when both were compared with the REST condition. These results provide evidence that the so-called dorsal route known to process visuospatial features can be recruited by auditory verbal stimuli. They also confirm previous reports indicating that some mental imagery tasks may not involve any significant participation of early visual areas.

Functional anatomy of a prelearned sequence of horizontal saccades in humans.

We have used positron emission tomography (PET) to study the functional anatomy of the repetition of a prelearned sequence of horizontal saccadic eye movements. Five subjects had to memorize a sequence of six successive horizontal saccades. The subjects were scanned in total darkness under three different conditions: at rest, during the execution of self-paced horizontal saccades, and while repeating a prelearned saccades sequence. The repetition of the prelearned saccades sequence led to specific normalized regional cerebral blood flow (NrCBF) increases at the depth of the superior frontal sulcus as well as at the rostral part of the supplementary motor area, whereas at the parietal level an important activation was observed in the intraparietal sulcus extending up to the precuneus. In addition, it was noticed that compared with the resting control condition, both oculomotor tasks activated a common set of cortical and subcortical areas. At the cortical level, this network was composed of the frontal eye fields, the supplementary eye fields, the median part of the cingulate gyrus, and the insula. At the subcortical level, the lenticular nucleus and the thalamus as well as the cerebellar vermis were activated consistently. A direct comparison of our results with those of other PET studies on spatial vision suggest that the dorsal visuospatial pathway could be extended toward the frontal premotor region. In such a scheme, visuospatial information computed in the intraparietal sulcus would be transmitted to the frontal premotor cortex to optimize a spatial-oriented behavior. This is consistent with the early proposal that perceptual and intentional components of spatial information are mediated through superior parietal and frontal areas, respectively.

Tremor and voluntary repetitive movement in Parkinson's disease: comparison before and after L-dopa with positron emission tomography.

Brain regions involved in tremor and voluntary movement were compared in seven subjects with hemiparkinsonian tremor using positron emission tomography and the [15O] water bolus activation method. Repeated measurements of the regional cerebral blood flow were performed both before and after tremor arrest induced by administration of L-dopa as well as during voluntary repetitive movements of the hand contralateral to tremor side. The normalized regional cerebral blood flow (NrCBF) was measured in regions of interest with anatomical boundaries that were defined for each subject by means of a three-dimensional reconstruction of magnetic resonance imaging data. Taking the rest after L-dopa as a control condition, NrCBF increased during tremor in a network of regions including the precentral (mean +/- SD 5.36 +/- 4.6%, P = 0.006) and paracentral (6.11 +/- 6%, P = 0.01) gyri contralateral to tremor side, the supplementary motor area (SMA; 4.03 +/- 4%, P = 0.02, n = 8 pairs), and the cerebellar vermis (8.64 +/- 9.9%, P = 0.01, n = 12). During voluntary repetitive movement of the hand contralateral to tremor compared with rest after L-dopa, the same patients activated the precentral (8.25 +/- 2.6%, P = 0.0006) and postcentral regions contralateral to movement (8.43 +/- 3.7%, P = 0.002), and the cerebellar cortex (3.49 +/- 2.1%, P = 0.03), precentral (3.58 +/- 3.1%, P = 0.04), and paracentral (4.03 +/- 3.6%, P = 0.04) regions ipsilateral to movement. The cerebellar vermis was activated (8.15 +/- 5.6%, P = 0.02, n = 8) as well as the SMA, but not significantly at the 0.05 level (5.16 +/- 5%, P = 0.08, n = 5). These results confirm the similarities of brain structures involved in parkinsonian tremor and voluntary movement and provide an anatomofunctional substrate for their clinical interactions.

Intersubject variability in functional neuroanatomy of silent verb generation: assessment by a new activation detection algorithm based on amplitude and size information.

We present an experimental evaluation of a new algorithm for the detection of activated areas in brain functional maps. The new algorithm, named HMSD, is based on a hierarchical multiscale description of the difference image in terms of connected objects. Size and magnitude of each object are simultaneously tested with respect to a bidimensional frequency distribution derived using Monte-Carlo simulations under the null hypothesis. In the present work. HMSD was applied to the analysis of a silent verb generation PET activation protocol conducted in six right-handed subjects. Applied to single-subject data. HMSD reveals activation located in the left inferior frontal gyrus in three subjects (two in the pars opercularis, one in the pars triangularis), and in the pars opercularis of the right inferior frontal gyrus in one case, the latter being combined to a crossed cerebellar activation. Overall, single-case results were consistent with the analyses of stereotactically averaged data. Despite a 2D implentation. HMSD detection performances of averaged data were better than that obtained with the 2D version of statistical parametric mapping (SPM) and comparable to that of the 3D version of SPM.

Functional neuroanatomy of the human visual fixation system.

The regional cerebral blood flow correlates of the active fixation of an imagined target were studied in five healthy humans using the positron emission tomography activation paradigm. The fixation task was contrasted to a passive control condition, both tasks being performed in total darkness. Blood flow increases were observed in the frontal eye fields and supplementary eye fields and in the median cingulate gyrus. We suggest that the network of these activated regions mediates the interactions between ocular fixation, eye movements and directed visual attention.

A positron emission tomography study of visual and mental spatial exploration.

We measured normalized regional cerebral blood flow (NrCBF) using positron emission tomography (PET) and oxygen-15-labeled water in eight young right-handed healthy volunteers selected as high-imagers. during 2 runs of 3 different conditions: 1, rest in total darkness 2; visual exploration of a map 3; mental exploration of the same map in total darkness. NrCBF images were aligned with individual magnetic resonance images (MRI), and NrCBF variations between pairs of measurements (N = 15) were computed in regions of interest having anatomical boundaries that were defined using a three-dimensional (3-D) reconstruction of each subject MRI. During visual exploration, we found bilateral activations of primary visual areas, superior and inferior occipital gyri, fusiform and lingual gyri, cuneus and precuneus, bilateral superior parietal, and angular gyri. The right lateral premotor area was also activated during this task while superior temporal gyri and Broca's area were deactivated. By contrast, mental exploration activated the right superior occipital cortex, the supplementary motor area, and the cerebellar vermis. No activation was observed in the primary visual area. These results argue for a specific participation of the superior occipital cortex in the generation and maintenance of visual mental images.

A positron emission tomography study of oculomotor imagery.

Focal increases of regional cerebral blood flow (rCBF) were measured by positron emission tomography in order to study the anatomo-functional analogies between imagined and executed saccadic eye movements. Oculomotor imagery was performed in the absence of overt eye movements. Compared with a control state the two conditions were associated with normalized rCBF increases in the median cingulate gyrus, and the supplementary and frontal eye fields of both hemispheres. Therefore in the human brain execution and mental imagery of eye movement appear to be functionally linked and mediated by a common network of frontal structures.

Location of hand function in the sensorimotor cortex: MR and functional correlation.

PURPOSE: To determine the location of hand function in the sensorimotor cortex using MR and positron emission tomography imaging studies. METHODS: Anatomic and physiological methods were used for this study. Anatomic study was based on the MR analysis of 22 subjects. The length of the sensorimotor cortex was measured in the axial and sagittal planes. Physiologic study was based on the positron emission tomography studies of 4 subjects. Each of the studies was correlated with MR. RESULTS: We found that the superior genu of the central sulcus corresponds to hand function in the sensorimotor cortex. This level may prove useful for any clinical correlations or for surgery. CONCLUSIONS: From this study, the hand function area in the sensorimotor cortex is easily understood with its characteristic shape in axial MR scan. The comparison of MR and positron emission tomography data clearly show anatomic correlations. This may be applied to the functional mapping of the pathologic studies in the sensorimotor cortex regions.

Abnormal regional CBF response in left hemisphere of dysphasic children during a language task.

This study used xenon 133 inhalation and single-photon computed tomography to measure regional cerebral blood flow during a quiet resting condition, a simple auditory task, and an auditory phonemic discrimination task in 3 age-matched groups of children suffering from developmental language disabilities: expressive dysphasia, expressive-receptive dysphasia, and attention-deficit hyperactivity disorder. An absence of left hemisphere activation was observed in the expressive-receptive group during the phonemic discrimination task as compared to both expressive and attention-deficit hyperactivity disorder children, together with an absence of left inferior parietal region activation in dysphasics as compared to hyperactive children. These results favor the hypothesis of an abnormal lateralization for language in dysphasic children and point toward possible different pathologic localizations in the different clinical subtypes of dysphasia.