Multimodal Fingerprints of Resting State Networks as assessed by Simultaneous Trimodal MR-PET-EEG Imaging.

Simultaneous MR-PET-EEG (magnetic resonance imaging - positron emission tomography - electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here for the first time. It enables the assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. Here, we characterize the brain's default mode network (DMN) in healthy male subjects using multimodal fingerprinting by quantifying energy metabolism via 2- [18F]fluoro-2-desoxy-D-glucose PET (FDG-PET), the inhibition - excitation balance of neuronal activation via magnetic resonance spectroscopy (MRS), its functional connectivity via fMRI and its electrophysiological signature via EEG. The trimodal approach reveals a complementary fingerprint. Neuronal activation within the DMN as assessed with fMRI is positively correlated with the mean standard uptake value of FDG. Electrical source localization of EEG signals shows a significant difference between the dorsal DMN and sensorimotor network in the frequency range of δ, θ, α and ß-1, but not with ß-2 and ß-3. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.

Towards improved hardware component attenuation correction in PET/MR hybrid imaging.

In positron emission tomography/computed tomography (PET/CT) hybrid imaging attenuation correction (AC) of the patient tissue and patient table is performed by converting the CT-based Hounsfield units (HU) to linear attenuation coefficients (LAC) of PET. When applied to the new field of hardware component AC in PET/magnetic resonance (MR) hybrid imaging, this conversion method may result in local overcorrection of PET activity values. The aim of this study thus was to optimize the conversion parameters for CT-based AC of hardware components in PET/MR. Systematic evaluation and optimization of the HU to LAC conversion parameters has been performed for the hardware component attenuation map (µ-map) of a flexible radiofrequency (RF) coil used in PET/MR imaging. Furthermore, spatial misregistration of this RF coil to its µ-map was simulated by shifting the µ-map in different directions and the effect on PET quantification was evaluated. Measurements of a PET NEMA standard emission phantom were performed on an integrated hybrid PET/MR system. Various CT parameters were used to calculate different µ-maps for the flexible RF coil and to evaluate the impact on the PET activity concentration. A 511 keV transmission scan of the local RF coil was used as standard of reference to adapt the slope of the conversion from HUs to LACs at 511 keV. The average underestimation of the PET activity concentration due to the non-attenuation corrected RF coil in place was calculated to be 5.0% in the overall phantom. When considering attenuation only in the upper volume of the phantom, the average difference to the reference scan without RF coil is 11.0%. When the PET/CT conversion is applied, an average overestimation of 3.1% (without extended CT scale) and 4.2% (with extended CT scale) is observed in the top volume of the NEMA phantom. Using the adapted conversion resulting from this study, the deviation in the top volume of the phantom is reduced to -0.5% and shows the lowest standard deviation inside the phantom in comparison to all other conversions. Simulation of a µ-map misregistration shows acceptable results for shifts below 5 mm for the flexible surface RF coil. The adapted conversion from HUs to LAC at 511 keV within this study can improve hardware component AC in PET/MR hybrid imaging as shown for a flexible RF surface coil. Furthermore, these results have a direct impact on the improvement of the hardware component AC of the examined flexible RF coil in conjunction with position determination.

The effect of MR surface coils on PET quantification in whole-body PET/MR: results from a pseudo-PET/MR phantom study.

PURPOSE: The use of magnetic resonance (MR) radiofrequency (RF) surface coils is a prerequisite for high-quality positron emission tomography (PET)/MR imaging. In lack of in-gantry transmission (TX) sources, the exact position of the RF coils is unknown in PET/MR, and may, therefore, lead to false attenuation correction (AC) of the emission (EM) data. The authors assess lesion and background quantification in AC-PET by mimicking different PET/MR imaging situations using a whole-body (WB) PET-only tomograph. METHODS: Phantom experiments were performed on a PET tomograph with 68 Ge-rod TX sources. First, a 15-cm plastic cylinder was filled uniformly with [18F]-FDG to simulate a head study. Second, a NEMA NU-2001 image quality phantom (35 x 25 x 25 cm3) was filled uniformly with [18F]-FDG to simulate torso imaging. The phantom contained six lesions (10-38 mm diameter, lesion-to-background ratio 6:1) centred around a 5 cm diameter lung insert. EM and TX measurements were acquired with and without MR head (cylinder) and surface (NU-2001 phantom) RF coils in place. The following imaging situations were mimicked in both head and torso phantom studies: (1) PET scan without MR coils in EM and TX for reference, (2) PET scan with coils in both EM and TX, and (3) PET scan with coils in EM but without coils in TX. Two more set-ups were performed for the torso phantom: (4) PET scan with coils in EM only and phantom shifted slightly compared to (3), and (5) PET scan with coils in EM and TX following local displacement of the surface coils. PET EM data (1)-(4) were corrected for attenuation and scatter using cold TX data. Imaging situations (1)-(3) were repeated with the cylinder phantom and head coil in a combined PET/MR prototype system employing template-based AC. RESULTS: Head phantom: In case the MR head coils were not accounted for during AC (3), central and peripheral background activity concentration was underestimated by 13%-19% when compared to the reference setup (1). The effects of MR coil omission during AC was replicated in the repeat study with the combined PET/MR prototype. Torso phantom: All lesions were equally visible on all AC-PET images. The effects of disregarding MR surface RF coils during AC [(3) vs (1)] were 4%, or less. A slightly higher bias was observed when accounting for the RF surface coils that were shifted between EM and TX (5). The effect of coil misalignment and neglect during AC on the quantification of the simulated lungs was insignificant compared to the noise levels in AC-PET. CONCLUSIONS: Unaccounted attenuation from MR surface coils causes a regional bias of AC-PET data in body regions near the MR coils. Bias of central regions was more noticeable in smaller-size objects. In torso studies with body surface coils, the visibility of central lesions on PET was unaffected by MR coils following incomplete AC. Coil misalignment of several cm between emission and attenuation images causes an error that was comparable to that arising from unaccounted MR coil attenuation but small compared to the average standard deviation of the activity concentration levels.

High resolution BrainPET combined with simultaneous MRI.

UNLABELLED: After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Jülich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. MATERIAL, METHODS: The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. RESULTS: Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. DISCUSSION, CONCLUSION: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.

PET imaging problems with the non-standard positron emitters Yttrium-86 and Iodine-124.

AIM: Positron emission tomography (PET) imaging of non-standard positron emitters is influenced by gamma-coincidences, i.e. false coincidences produced by the coincident detection of an annihilation photon and a gamma-ray simultaneously emitted with the positron. The extent to which the PET study is disturbed by this effect is dependent on the kind of the positron emitter used, the kind and position of the object, the acquisition mode, i.e. the optional use of septa, and the reconstruction program. In order to demonstrate and study imaging problems with non-standard positron emitters, a phantom was scanned containing non-radioactive rods with different absorption materials and filled with either (124)I or (86)Y in the bidimensional (2D) as well as tridimensional (3D) acquisition mode. METHODS: For reconstruction, the PET manufacturer's standard software without any modification was used. To reduce errors caused by the gamma-coincidences, a simple linear background subtraction, estimated from the counts at the scanner's external radius, was applied. RESULTS: Without background subtraction, apparent positive and negative ''radioactivity concentrations'' were found in regions of interest positioned over the non-radioactive rods with values higher for (86)Y compared to (124)I and also higher for 3D compared to 2D. A complete subtraction of the background led to erroneous RESULTS: The errors in the phantom's non-radioactive rods and the difference between measured and true radioactivity became minimum, when about 75% of the background was subtracted. This refers to both the 2D and 3D mode. CONCLUSION: Quantitation problems with the non-standard positron emitters (124)I and (86)Y could be minimized in the phantom study examined here by using a simple background subtraction together with the manufacturer's standard correction and reconstruction procedures.

Visual cortex activation in kinesthetic guidance of reaching.

The purpose of this research was to determine the cortical circuit involved in encoding and controlling kinesthetically guided reaching movements. We used (15)O-butanol positron emission tomography in ten blindfolded able-bodied volunteers in a factorial experiment in which arm (left/right) used to encode target location and to reach back to the remembered location and hemispace of target location (left/right side of midsagittal plane) varied systematically. During encoding of a target the experimenter guided the hand to touch the index fingertip to an external target and then returned the hand to the start location. After a short delay the subject voluntarily moved the same hand back to the remembered target location. SPM99 analysis of the PET data contrasting left versus right hand reaching showed increased (P < 0.05, corrected) neural activity in the sensorimotor cortex, premotor cortex and posterior parietal lobule (PPL) contralateral to the moving hand. Additional neural activation was observed in prefrontal cortex and visual association areas of occipital and parietal lobes contralateral and ipsilateral to the reaching hand. There was no statistically significant effect of target location in left versus right hemispace nor was there an interaction of hand and hemispace effects. Structural equation modeling showed that parietal lobe visual association areas contributed to kinesthetic processing by both hands but occipital lobe visual areas contributed only during dominant hand kinesthetic processing. This visual processing may also involve visualization of kinesthetically guided target location and use of the same network employed to guide reaches to visual targets when reaching to kinesthetic targets. The present work clearly demonstrates a network for kinesthetic processing that includes higher visual processing areas in the PPL for both upper limbs and processing in occipital lobe visual areas for the dominant limb.

Assessment of the short-lived non-pure positron-emitting nuclide (120)I for PET imaging.

PURPOSE: The non-pure positron-emitting iodine isotope (120)I (T(1/2)=81 min) is a short-lived alternative to (124)I. (120)I has a positron abundance more than twice that of (124)I and a maximum positron energy of 4 MeV. This study was undertaken to evaluate and characterise the qualitative and quantitative PET imaging of (120)I. METHODS: (120)I was produced via the (120)Te(p,n) reaction on highly enriched (120)Te. The measurements were done with the Siemens scanner HR+ and the 2D PET scanner GE PC4096+. A cylinder containing three cold inserts and a phantom resembling a human brain slice were used to evaluate half-life, positron abundance and background correction. To analyse the image resolution, a -mm tube placed in water was filled with (120)I and (18)F. Comparisons with (18)F, (124)I and (123)I (measured with SPECT) were made using the Hoffman 3D brain phantom. RESULTS: The half-life of 81.1 min was reproduced by the PET measurements. The PET-based positron abundance ranged from 47.9% to 55.0%. The reconstructed image resolution found with the HR+ was 5.4 mm FWHM (12.3 mm FWTM), in contrast to 4.6 mm (8.6 mm) when using (18)F. Erroneous positive and negative numbers of radioactivity found in the cold inserts became nearly zero when the background of gamma-coincidences was corrected for. Images of the Hoffman phantom were inferior to those obtained when (18)F or (124)I was applied but superior to the (123)I-SPECT images. CONCLUSION: Our data show that (120)I of high radionuclidic purity can be regarded as a suitable nuclide for the PET imaging of radioiodine-labelled pharmaceuticals.

Conscious and subconscious sensorimotor synchronization--prefrontal cortex and the influence of awareness.

One of the most compelling challenges for modern neuroscience is the influence of awareness on behavior. We studied prefrontal correlates of conscious and subconscious motor adjustments to changing auditory rhythms using regional cerebral blood flow measurements. At a subconscious level, movement adjustments were performed employing bilateral ventral mediofrontal cortex. Awareness of change without explicit knowledge of the nature of change led to additional ventral prefrontal and premotor but not dorsolateral prefrontal activations. Only fully conscious motor adaptations to a changing rhythmic pattern showed prominent involvement of anterior cingulate and dorsolateral prefrontal cortex. These results demonstrate that while ventral prefrontal areas may be engaged in motor adaptations performed subconsciously, only fully conscious motor control which includes motor planning will involve dorsolateral prefrontal cortex.

Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities.

In this study, we aimed to characterize commonalities and differences of activation patterns during verbal episodic memory processes across different presentation modalities (visual or auditory) and different imagery content (low or high) of the presented verbal memory items. Twelve right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol positron emission tomography scans. In six of the subjects the verbal material was presented visually, and in six subjects auditorily. The subjects had to encode and retrieve two sets of 12 word-pair associates of high (set 1) or low (set 2) imagery content (not semantically related). The presentation of nonsense words served as reference condition. Images were analyzed with statistical parametric mapping. Conjunction analysis was used to identify commonalities, and cognitive subtraction analysis was used to identify differences. The use of conjunction analyses enabled us to identify commonly activated regions involved in episodic encoding and retrieval of verbal material irrespective of the presentation modality or the imagery content. Our results add further evidence to recent findings that bilateral prefrontal activations are important for episodic retrieval and thus the role of the left prefrontal cortex has been underestimated during episodic retrieval. Furthermore, our results support the idea of functionally segregated areas in the prefrontal cortex. Finally, our results provide strong evidence that mesial parietal cortex (precuneus) involvement is not restricted to processes involving imagery.

Interdependence of regional and global cerebral blood flow during visual stimulation: an O-15-butanol positron emission tomography study.

The authors investigated the influence of variations in global cerebral blood flow (gCBF) on regional flow changes during visual stimulation. Global flow was varied using different end-expiratory CO2 values (PETCO2) between 20 and 70 mm Hg. Visual stimulation was performed with a red LED-array flashing at 8 Hz. Blood flow was measured with 0-15-butanol, continuous arterial blood sampling, and positron emission tomography (PET). Global flow changes surpassed the published values of O-15-H2O studies, better fitting the results of the inert gas technique (gCBF at 20, 40, and 70 mm Hg PETCO2 +/- SD was 31 +/- 4, 48 +/- 13, and 160 +/- 50 mL 100 g(-1) min(-1), respectively). The relation between PETCO2 and CBF in the current study was best described by an exponential rather than a linear function. At low PETCO2, the activation-induced flow changes are moderately damped, whereas at high PETCO2, they are nearly lost (deltaCBF (+/-SD): 52% +/- 25%, 68% +/- 22%, 16% +/- 25% at PETCO2 = 20, 40, 70 mm Hg, respectively).

Neural correlates of religious experience.

The commonsense view of religious experience is that it is a preconceptual, immediate affective event. Work in philosophy and psychology, however, suggest that religious experience is an attributional cognitive phenomenon. Here the neural correlates of a religious experience are investigated using functional neuroimaging. During religious recitation, self-identified religious subjects activated a frontal-parietal circuit, composed of the dorsolateral prefrontal, dorsomedial frontal and medial parietal cortex. Prior studies indicate that these areas play a profound role in sustaining reflexive evaluation of thought. Thus, religious experience may be a cognitive process which, nonetheless, feels immediate.

The motion aftereffect: more than area V5/MT? Evidence from 15O-butanol PET studies.

The motion aftereffect is a perceptual phenomenon which has been extensively investigated both psychologically and physiologically. Neuroimaging techniques have recently demonstrated that area V5/MT is activated during the perception of this illusion. The aim of this study was to test the hypothesis if a more broadly distributed network of brain regions subserves the motion aftereffect. To identify the neuronal structures involved in the perception of the motion aftereffect, regional cerebral blood flow (rCBF) measurements with positron emission tomography were performed in six normal volunteers. Data were analysed using SPM96. The motion-sensitive visual areas including area V5/MT were activated in both hemispheres. Additionally, the lateral parietal cortex bilaterally, the right dorsolateral prefrontal cortex, the anterior cingulate cortex and the left cerebellum showed significant increases in rCBF values during the experience of the waterfall illusion. In a further reference condition with identical attentional demand but no perception of a motion aftereffect elevated rCBF were found in these regions as well. In conclusion, our findings support the notion that the perceptual illusion of motion arises exclusively in the motion-sensitive visual area V5/MT. In addition, a more widespread network of brain regions including the prefrontal and parietal cortex is activated during the waterfall illusion which represents a non-motion aftereffect-specific subset of brain areas but is involved in more basic attentional processing and cognition.

Neural consequences of acting in near versus far space: a physiological basis for clinical dissociations.

We used PET to determine which brain regions are implicated when normal volunteers bisect horizontal lines and point to dots in near (peripersonal) or far (extrapersonal) space. Studies of line bisection in patients with right hemisphere lesions have shown that bisection performance can be severely impaired in either near or far space while remaining within normal limits in the other spatial domain. Likewise, clinical dissociations between pointing to objects in near and far space have been reported. The normal functional anatomy of these dissociations has not been demonstrated convincingly. Regional cerebral blood flow measurements using PET were carried out in 12 healthy right-handed male volunteers who bisected lines or pointed to dots in near or far space, using a laser pen. Subjects performing either task in near space showed neural activity in the left dorsal occipital cortex, left intraparietal cortex, left ventral premotor cortex and left thalamus. In far space, subjects performing either task showed activation of the ventral occipital cortex bilaterally and the right medial temporal cortex. These data provide physiological support for the clinically observed dissociations demonstrating that attending to and acting in near space differentially employs dorsal visuomotor processing areas, whereas attending to and acting in far space differentially draws on ventral visuoperceptual processing areas, even when the motor components of the tasks are identical when performed in the two spaces.

Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation.

We studied the effect of repetitive transcranial magnetic stimulation (rTMS) on changes in regional cerebral blood flow (rCBF) as revealed by positron emission tomography (PET) while subjects performed a 2-back verbal working memory (WM) task. rTMS to the right or left dorsolateral prefrontal cortex (DLPFC), but not to the midline frontal cortex, significantly worsened performance in the WM task while inducing significant reductions in rCBF at the stimulation site and in distant brain regions. These results for the first time demonstrate the ability of rTMS to produce temporary functional lesions in elements of a neuronal network thus changing its distributed activations and resulting in behavioral consequences.

Functional anatomy of intrinsic alertness: evidence for a fronto-parietal-thalamic-brainstem network in the right hemisphere.

Alertness, the most basic intensity aspect of attention, probably is a prerequisite for the more complex and capacity demanding domains of attention selectivity. Behaviorally, intrinsic alertness represents the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time measurements without preceding warning stimuli. Up until now only parts of the cerebral network subserving alertness have been revealed in animal, lesion, and functional imaging studies. Here, in a 15O-butanol PET activation study in 15 right-handed young healthy male volunteers for this basic attention function we found an extended right hemisphere network including frontal (anterior cingulate-dorsolateral cortical)-inferior parietal-thalamic (pulvinar and possibly the reticular nucleus) and brainstem (ponto-mesencephalic tegmentum, possibly involving the locus coeruleus) structures, when subjects waited for and rapidly responded to a centrally presented white dot by pressing a response key with the right-hand thumb.

Episodic retrieval activates the precuneus irrespective of the imagery content of word pair associates. A PET study.

The aim of this study was to evaluate further the role of the precuneus in episodic memory retrieval. The specific hypothesis addressed was that the precuneus is involved in episodic memory retrieval irrespective of the imagery content. Two groups of six right-handed normal male volunteers took part in the study. Each subject underwent six [15O]butanol-PET scans. In each of the six trials, the memory task began with the injection of a bolus of 1500 MBq of [15O]butanol. For Group 1, 12 word pair associates were presented visually, for Group 2 auditorily. The subjects of each group had to learn and retrieve two sets of 12 word pairs each. One set consisted of highly imaginable words and another one of abstract words. Words of both sets were not related semantically, representing 'hard' associations. The presentations of nonsense words served as reference conditions. We demonstrate that the precuneus shows consistent activation during episodic memory retrieval. Precuneus activation occurred in visual and auditory presentation modalities and for both highly imaginable and abstract words. The present study therefore provides further evidence that the precuneus has a specific function in episodic memory retrieval as a multimodal association area.

Encoding and retrieval in declarative learning: a positron emission tomography study.

We present neuroanatomical correlates of encoding and retrieval in an episodic memory task using visually presented highly imaginable word-pair associates. A total of 13 right-handed normal male volunteers took part in the study. Each subject underwent six (15)O-butanol PET scans. On each of the six trials the memory task began 30 s before the injection of a bolus of (15)O-butanol. The subjects had to learn and retrieve 12 word pairs (highly imaginable words, not semantically related, hard associations). The presentation of nonsense words served as a reference condition. Recall accuracy after 2-4 presentations was 66.1%+/-21.1 correct during the PET measurement so that scanning during the retrieval of word pair associates was appropriate to capture the brain activity associated with retrieval. The results obtained support the hypothesis of the presence of an asymmetric network consisting of distributed brain structures subserving associative memory. We show left dorsolateral prefrontal activation during the encoding of visually presented word pair associates, whereas retrieval led to bilateral frontal activation. Furthermore, the importance of the precuneus in the retrieval of highly imaginable word-pair associates using visual imagery as a mnemonic strategy is demonstrated.

[O-15-butanol Pet activation study on the cerebral representation of declarative memory]. / O-15-Butanol-PET-Aktivierungsstudie zur zerebralen Repräsentation deklarativer Gedächtnisvorgänge.

AIM: In this study, neuroanatomical correlates of encoding and retrieval in paired associate learning were evaluated with positron emission tomography using auditorily presented highly imaginable words. METHODS: Six right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol PET scans. On each of the six trials the memory task began with the injection of a bolus of O-15-butanol. The subjects had to learn and retrieve twelve word pairs (highly imaginable words, not semantically related). The presentation of nonsense words served as reference condition. RESULTS: Recall accuracy after 2-4 presentations was high during the PET measurement. In both encoding and retrieval we found anterior cingulate activation. We show bilateral dorsolateral prefrontal activation during the encoding of auditorily presented word pair associates, whereas retrieval led to left frontal activation. Furthermore, we demonstrate the importance of the precuneus in the retrieval of highly imaginable word-pair associates. CONCLUSION: Our results support the hypothesis of the presence of distributed widespread brain structures subserving episodic declarative memory.

Role of the premotor cortex in recovery from middle cerebral artery infarction.

OBJECTIVE: To study the mechanisms underlying recovery from middle cerebral artery infarction in 7 patients with an average age of 53 years who showed marked recovery of hand function after acute severe hemiparesis caused by their first-ever stroke. INTERVENTIONS: Assessment of motor functions, transcranial magnetic stimulation, somatosensory evoked potentials, magnetic resonance imaging, and positron emission tomographic measurements of regional cerebral blood flow during finger movement activity. RESULTS: The infarctions involved the cerebral convexity along the central sulcus from the Sylvian fissure up to the hand area but spared the caudate nucleus, thalamus, middle and posterior portions of the internal capsule, and the dorsal part of the precentral gyrus in each patient. After recovery (and increase in motor function score of 57%, P<.001), the motor evoked potentials in the hand and leg muscles contralateral to the infarctions were normal, whereas the somatosensory evoked potentials from the contralateral median nerve were reduced. During fractionated finger movements of the recovered hand, regional cerebral blood flow increases occurred bilaterally in the dorsolateral and medial premotor areas but not in the sensorimotor cortex of either hemisphere. CONCLUSIONS: Motor recovery after cortical infarction in the middle cerebral artery territory appears to rely on activation of premotor cortical areas of both cerebral hemispheres. Thereby, short-term output from motor cortex is likely to be initiated.

Representations of graphomotor trajectories in the human parietal cortex: evidence for controlled processing and automatic performance.

The aim of this study was to identify the cerebral areas activated during kinematic processing of movement trajectories. We measured regional cerebral blood flow (rCBF) during learning, performance and imagery of right-hand writing in eight right-handed volunteers. Compared with viewing the writing space, increases in rCBF were observed in the left motor, premotor and frontomesial cortex, and in the right anterior cerebellum in all movement conditions, and the increases were related to mean tangential writing velocity. No rCBF increases occurred in these areas during imagery. Early learning of new ideomotor trajectories and deliberately exact writing of letters both induced rCBF increases in the cortex lining the right intraparietal sulcus. In contrast, during fast writing of overlearned trajectories and in the later phase of learning new ideograms the rCBF increased bilaterally in the posterior parietal cortex. Imagery of ideograms that had not been practised previously activated the anterior and posterior parietal areas simultaneously. Our results provide evidence suggesting that the kinematic representations of graphomotor trajectories are multiply represented in the human parietal cortex. It is concluded that different parietal subsystems may subserve attentive sensory movement control and whole-field visuospatial processing during automatic performance.