ASL-BIDS, the brain imaging data structure extension for arterial spin labeling.

Arterial spin labeling (ASL) is a non-invasive MRI technique that allows for quantitative measurement of cerebral perfusion. Incomplete or inaccurate reporting of acquisition parameters complicates quantification, analysis, and sharing of ASL data, particularly for studies across multiple sites, platforms, and ASL methods. There is a strong need for standardization of ASL data storage, including acquisition metadata. Recently, ASL-BIDS, the BIDS extension for ASL, was developed and released in BIDS 1.5.0. This manuscript provides an overview of the development and design choices of this first ASL-BIDS extension, which is mainly aimed at clinical ASL applications. Discussed are the structure of the ASL data, focussing on storage order of the ASL time series and implementation of calibration approaches, unit scaling, ASL-related BIDS fields, and storage of the labeling plane information. Additionally, an overview of ASL-BIDS compatible conversion and ASL analysis software and ASL example datasets in BIDS format is provided. We anticipate that large-scale adoption of ASL-BIDS will improve the reproducibility of ASL research.

ExploreASL: An image processing pipeline for multi-center ASL perfusion MRI studies.

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

Brain activity during phonation in healthy female singers with supraglottic compression: an fMRI pilot study.

This pilot study evaluated the usability of functional magnetic resonance imaging (fMRI) to detect brain activation during phonation in healthy female singers with supraglottic compression. Four healthy female classical singers (mean age: 26 years) participated in the study. All subjects had normal vocal folds and vocal characteristics and showed supraglottic compression. The fMRI experiment was carried out using a block design paradigm. Brain activation during phonation and exhalation was analyzed using Brain Voyager software (Brain Innovation B.V., Maastricht, The Netherlands). An fMRI data analysis showed a significant effect of phonation control in the bilateral pre/postcentral gyrus, and in the frontal, cingulate, superior and middle temporal gyrus, as well as in the parietal lobe, insula, lingual gyrus, cerebellum, thalamus and brainstem. These activation areas are consistent with previous reports using other fMRI protocols. In addition, a significant effect of phonation compared to exhalation control was found in the bilateral superior temporal gyrus, and the pre/postcentral gyrus. This fMRI pilot study allowed to detect a normal pattern of brain activity during phonation in healthy female singers with supraglottic compression using the proposed protocol. However, the pilot study detected problems with the experimental material/procedures that would necessitate refining the fMRI protocol. The phonation tasks were not capable to show brain activation difference between high-pitched and comfortable phonation. Further fMRI studies manipulating vocal parameters during phonation of the vowels /a/ and /i/ may elicit more distinctive hemodynamic response (HDR) activity patterns relative to voice modulation.

Concurrent Cortical Representations of Function- and Size-Related Object Affordances: An fMRI Study.

Previous work has shown that the perception of a graspable object may automatically potentiate actions that are tailored to specific action-related features of the object (e.g., its size) and may be related to its immediate grasping as well as to its long-term, functional use. We investigated the neural correlates of function- and size-related object affordances that may be concurrently potentiated by a graspable object. Participants were lying in a MR scanner holding a large switch in one hand and a small switch in the other hand. They passively attended a large or a small object with clearly separated functional and graspable end that was displayed centrally at an average angle of 45 degrees. Participants responded to the direction of an arrow that was overlaid on the object after a mean period of 1,000 ms after object onset and was pointing to the left or to the right with equal probability. Response times were shorter when the arrow pointed to the functional end of the object and when the responses were made with the switch that was congruent to the size of the perceived object. A clear distinction was found in the representation of function- and size-related affordances; the former was represented in the posterior parietal cortex and the latter in prefrontal, premotor, and primary sensorimotor cortices. We conclude that different aspects of object-directed actions may be automatically potentiated by individual object features and are represented in distinct brain areas.

Brain Activity During Phonation in Women With Muscle Tension Dysphonia: An fMRI Study.

OBJECTIVES: The main objectives of this functional magnetic resonance imaging (fMRI) study are (1) to investigate brain activity during phonation in women with muscle tension dysphonia (MTD) in comparison with healthy controls; and (2) to explain the neurophysiological mechanism of laryngeal hyperfunction/tension during phonation in patients with MTD. METHODS: Ten women with MTD and fifteen healthy women participated in this study. The fMRI experiment was carried out using a block design paradigm. Brain activation during phonation and exhalation was analyzed using BrainVoyager software. RESULTS: The statistical analysis of fMRI data has demonstrated that MTD patients control phonation by use of the auditory, motor, frontal, parietal, and subcortical areas similar to phonation control by healthy people. Comparison of phonation tasks in the two groups revealed higher brain activities in the precentral gyrus, inferior, middle and superior frontal gyrus, lingual gyrus, insula, cerebellum, midbrain, and brainstem as well as lower brain activities in the cingulate gyrus, superior and middle temporal gyrus, and inferior parietal lobe in the MTD group. No differences were found between the two groups regarding exhalation control. CONCLUSIONS: The findings in this study provide insight into phonation and exhalation control in patients with MTD. The imaging results demonstrated that in patients with MTD, altered (higher/lower) brain activities may result in laryngeal tension and vocal hyperfunction.

Functional Magnetic Resonance Imaging Study of Brain Activity Associated With Pitch Adaptation During Phonation in Healthy Women Without Voice Disorders.

OBJECTIVES: This functional magnetic resonance imaging (fMRI) study investigated the brain activity associated with pitch adaptation during phonation in healthy women without voice disorders. STUDY DESIGN: This is an interventional prospective study. METHODS: Sixteen healthy women (mean age: 24.3 years) participated in a blocked design fMRI experiment involving two phonation (comfortable phonation and high-pitched phonation) and exhalation (prolonged exhalation) tasks. BrainVoyager QX Version 2.4 software was used for group-level general linear model analysis (q[FDR] < 0.05). RESULTS: Analyses showed a significant main effect of phonation with pitch adaptation compared with rest period in the bilateral precentral gyrus, superior frontal gyrus, posterior cingulate gyrus, superior and middle temporal gyrus, insula and cerebellum, left middle and inferior frontal gyrus, right lingual gyrus, cingulate gyrus, and thalamus. Statistical results also identified a significant main effect of exhalation compared with rest period in the bilateral precentral gyrus, cerebellum, right lingual gyrus, thalamus, and left supramarginal gyrus. In addition, a significant main effect of phonation was found in the bilateral superior temporal gyrus and right insula, as well as in the left midbrain periaqueductal gray for high-pitched phonation only. CONCLUSIONS: We demonstrated that a blocked design fMRI is sensitive enough to define a widespread network of activation associated with phonation involving pitch variation. The results of this study will be implemented in our future research on phonation and its disorders.

Brachial plexus 3D reconstruction from MRI with dissection validation: a baseline study for clinical applications.

PURPOSE: The present study aimed to establish a baseline for detailed 3D brachial plexus reconstruction from magnetic resonance imaging (MRI). Concretely, the goal was to determine the individual brachial plexus anatomy with maximum detail and accuracy achievable, as yet irrespective of whether the methods used could be economically and practically applied in the clinical setting. MATERIALS AND METHODS: Six embalmed cadavers were randomly taken for MRI imaging of the brachial plexus. Detailed two-dimensional (2D) segmentation for all brachial plexus parts was done. The 2D brachial plexus segmentations were 3D reconstructed using Mimics(®) software. Then, these 3D reconstructions were anatomically validated by dissection of the cadavers. After finalising the cadaver experiments, brachial plexus MRIs were obtained in three healthy male volunteers and the same reconstruction procedure as in vitro was followed. RESULTS: A procedure was developed for brachial plexus 3D reconstruction based on MRI without the use of any contrast agent. Anatomical validation of six cadaver brachial plexus reconstructions showed high correspondence with the dissected brachial plexuses. Anatomical variations of the main branches were equally present in the 3D reconstructions generated. However, there were also some differences that related to the difference between the surface anatomy of the nerve and the internal nerve structure. In vivo, it was possible to reconstruct the complete brachial plexus in such a manner that normal-appearing BPs were derived in a reproducible way. CONCLUSIONS: This study showed that the described procedure results in accurate and reproducible brachial plexus 3D reconstructions.

MR pulse wave velocity increases with age faster in the thoracic aorta than in the abdominal aorta.

PURPOSE: To assess the difference between thoracic and abdominal aortic pulse wave velocity (PWV) in apparently healthy subjects including young adults to elderly subjects. MATERIALS AND METHODS: We performed PWV and distensibility measurements and analysis of thoracic and abdominal aortic segments in 96 apparently normal subjects aged 20-80 years with magnetic resonance (MR). Both unadjusted correlation and General Linear Model (GLM) analysis of log-transformed PWV (thoracic and abdominal aorta) and distensibility (four aortic cross-sections) were performed. RESULTS: Both thoracic and abdominal PWV values and distensibility values increased with age. In unadjusted analyses the correlation between the ln(thoracic PWV) and age (r = 0.71; P < 0.001) was stronger than between ln(abdominal PWV) and age (r = 0.50; P < 0.001). In GLM analysis, the only determinant of thoracic and abdominal PWV was age (F = 42.5 and F = 14.8, respectively; both P < 0.001). Similarly, correlation between ln(distensibility) and age was strong (r = -0.79, r = -0.67, r = -0.71, and r = -0.65 for ascending, descending, diaphragmatic, and low abdominal aorta, respectively; all P < 0.001). In GLM analysis, age was the major determinant for distensibility of the ascending aorta (F = 81.7; P < 0.001), descending aorta (F = 42.2; P < 0.001), diaphragmatic aorta (F = 39.2; P < 0.001), and low abdominal aorta (F = 32.8; P < 0.001). CONCLUSION: The thoracic aorta is less stiff than the abdominal aorta in young and middle-aged subjects, and stiffens more rapidly with age than the abdominal aorta, resulting in a stiffer thoracic than abdominal aorta at older age.

An anatomically validated brachial plexus contouring method for intensity modulated radiation therapy planning.

PURPOSE: To develop contouring guidelines for the brachial plexus (BP) using anatomically validated cadaver datasets. Magnetic resonance imaging (MRI) and computed tomography (CT) were used to obtain detailed visualizations of the BP region, with the goal of achieving maximal inclusion of the actual BP in a small contoured volume while also accommodating for anatomic variations. METHODS AND MATERIALS: CT and MRI were obtained for 8 cadavers positioned for intensity modulated radiation therapy. 3-dimensional reconstructions of soft tissue (from MRI) and bone (from CT) were combined to create 8 separate enhanced CT project files. Dissection of the corresponding cadavers anatomically validated the reconstructions created. Seven enhanced CT project files were then automatically fitted, separately in different regions, to obtain a single dataset of superimposed BP regions that incorporated anatomic variations. From this dataset, improved BP contouring guidelines were developed. These guidelines were then applied to the 7 original CT project files and also to 1 additional file, left out from the superimposing procedure. The percentage of BP inclusion was compared with the published guidelines. RESULTS: The anatomic validation procedure showed a high level of conformity for the BP regions examined between the 3-dimensional reconstructions generated and the dissected counterparts. Accurate and detailed BP contouring guidelines were developed, which provided corresponding guidance for each level in a clinical dataset. An average margin of 4.7 mm around the anatomically validated BP contour is sufficient to accommodate for anatomic variations. Using the new guidelines, 100% inclusion of the BP was achieved, compared with a mean inclusion of 37.75% when published guidelines were applied. CONCLUSION: Improved guidelines for BP delineation were developed using combined MRI and CT imaging with validation by anatomic dissection.

Human left ventral premotor cortex mediates matching of hand posture to object use.

Visuomotor transformations for grasping have been associated with a fronto-parietal network in the monkey brain. The human homologue of the parietal monkey region (AIP) has been identified as the anterior part of the intraparietal sulcus (aIPS), whereas the putative human equivalent of the monkey frontal region (F5) is located in the ventral part of the premotor cortex (vPMC). Results from animal studies suggest that monkey F5 is involved in the selection of appropriate hand postures relative to the constraints of the task. In humans, the functional roles of aIPS and vPMC appear to be more complex and the relative contribution of each region to grasp selection remains uncertain. The present study aimed to identify modulation in brain areas sensitive to the difficulty level of tool object - hand posture matching. Seventeen healthy right handed participants underwent fMRI while observing pictures of familiar tool objects followed by pictures of hand postures. The task was to decide whether the hand posture matched the functional use of the previously shown object. Conditions were manipulated for level of difficulty. Compared to a picture matching control task, the tool object - hand posture matching conditions conjointly showed increased modulation in several left hemispheric regions of the superior and inferior parietal lobules (including aIPS), the middle occipital gyrus, and the inferior temporal gyrus. Comparison of hard versus easy conditions selectively modulated the left inferior frontal gyrus with peak activity located in its opercular part (Brodmann area (BA) 44). We suggest that in the human brain, vPMC/BA44 is involved in the matching of hand posture configurations in accordance with visual and functional demands.

Praxis and language are linked: evidence from co-lateralization in individuals with atypical language dominance.

We determined the neural correlates of word generation and tool use pantomiming in healthy subjects with typical (n=10) or atypical (n=10) language dominance to investigate similarities in response pattern and hemispheric specialization between language and praxis. All typical language dominant volunteers also revealed left hemisphere changes during tool use pantomiming in prefrontal, premotor, and posterior parietal regions. All atypical language dominant participants displayed right hemisphere engagement for tool use. Co-lateralization of the language and praxis networks was observed on group and individual level, regardless of the participant's handedness. Activation maps of the word generation and tool use pantomiming contrasts displayed overlap in five cortical regions: supplementary motor area, dorsal and ventral premotor cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. Individual lateralization indices were calculated for each region and revealed significant positive group correlations between .51 and .95 with every other region within the paradigms. Positive cross-task correlations ranged between .72 (supplementary motor complex) and .97 (dorsal premotor cortex) and illustrate that the strength of hemispheric specialization of one task significantly predicts the side and degree of lateralization of the other task, suggesting a functional and topographic link between language and praxis. These findings support models that link gestures and speech to explain the evolution of human language. We argue that the existence of a common and co-lateralized network underlying the production of complex learned movement, whether it be speech or tool use, may represent the evolutionary remnant of a neural system out of which proto-sign and proto-speech co-evolved.

Influence of perspective on the neural correlates of motor resonance during natural action observation.

We investigated the neural correlates of motor resonance during the observation of natural transitive actions and determined how the observer's perspective modulates the neural activation. Seventeen right-handed participants observed right and left hand tool grasping actions from a first-person or third-person perspective while undergoing fMRI. A two-factorial analysis of variance over the parietal region revealed no main effects of hand identity or perspective, but unveiled a hand by perspective interaction effect. The first-person perspective elicited parietal activation in the hemisphere contralateral to the performing hand as if the modelled action was mimicked with the same anatomical hand. In the third-person perspective, parietal activation ipsilateral to the modelled hand was found, indicating a specular strategy, rather than an anatomical imitation. Motor resonance was maximal in three foci in the superior parietal lobule and intraparietal sulcus that have been associated with prehensile actions. Our results suggest that therapeutic strategies aimed to elicit motor resonance, such as motor imagery and observational modelling, can adjust their spatial frame of reference according to the hemisphere they intend to stimulate.

Quantifying hemodynamic refractory bold effects in normal subjects at the single-subject level using an inverse logit fitting procedure.

PURPOSE: To evaluate whether hemodynamic refractory effects provoked by repeated visual stimulation can be detected and quantified at the single-subject level using a recently described hemodynamic response function (HRF) fitting algorithm. MATERIALS AND METHODS: Hemodynamic refractory effects were induced with an easily applicable functional MRI (fMRI) paradigm. A fitting method with inverse logit (IL) functions was applied to quantify net HRFs at the single-subject level with three interstimulus intervals (ISI; 1, 2, and 6 s). The model yielded amplitude, latencies, and width for each HRF. RESULTS: HRF fitting was possible in 44 of 51 healthy volunteers, with excellent goodness-of-fit (R(2) = 0.9745 ± 0.0241). Refractory effects were most pronounced for the 1-s ISI (P < 0.001) and had nearly disappeared for the 6-s ISI. CONCLUSION: Quantifying refractory effects in individuals was possible in 86.3% of normal subjects using the IL fitting algorithm. This setup may be suitable to explore such effects in individual patients.

Cerebral lateralization of praxis in right- and left-handedness: same pattern, different strength.

We aimed to investigate the effect of hand effector and handedness on the cerebral lateralization of pantomiming learned movements. Fourteen right-handed and 14 left-handed volunteers performed unimanual and bimanual tool-use pantomimes with their dominant or nondominant hand during fMRI. A left hemispheric lateralization was observed in the right- and left-handed group regardless of which hand(s) performed the task. Asymmetry was most marked in the dorsolateral prefrontal cortex (DLPFC), premotor cortex (PMC), and superior and inferior parietal lobules (SPL and IPL). Unimanual pantomimes did not reveal any significant differences in asymmetric cerebral activation patterns between left- and right-handers. Bimanual pantomimes showed increased left premotor and posterior parietal activation in left- and right-handers. Lateralization indices (LI) of the 10% most active voxels in DLPFC, PMC, SPL, and IPL were calculated for each individual in a contrast that compared all tool versus all control conditions. Left-handers showed a significantly reduced overall LI compared with right-handers. This was mainly due to diminished asymmetry in the IPL and SPL. We conclude that the recollection and pantomiming of learned gestures recruits a similar left lateralized activation pattern in right and left-handed individuals. Handedness only influences the strength (not the side) of the lateralization, with left-handers showing a reduced degree of asymmetry that is most readily observed over the posterior parietal region. Together with similar findings in language and visual processing, these results point to a lesser hemispheric specialization in left-handers that may be considered in the cost/benefit assessment to explain the disproportionate handedness polymorphism in humans.

Absence of haemodynamic refractory effects in patients with migraine without aura: an interictal fMRI study.

BACKGROUND: In healthy controls, haemodynamic refractory effects are observed with blood-oxygenation-level dependent (BOLD) functional MRI (fMRI): the haemodynamic response function (HRF) to the second stimulus in a pair of stimuli with short interstimulus interval (ISI) shows a decreased amplitude and an increased time-to-peak. We hypothesize that there may be interictal haemodynamic abnormalities in migraineurs. METHODS: An event-related fMRI design with paired face stimuli and varying ISIs was used to measure interictal HRFs in the face recognition area of patients with migraine without aura (MwoA) and controls. Net responses to the second stimulus in a pair were calculated and averaged per participant. Several characterizing parameters of the net responses were quantified and examined within each group. RESULTS: Refractory effects were not observed in our patient group. There are no changes in the net responses compared with the reference situation in patients, irrespective of the ISI, whereas in controls all HRF parameters are decreased or delayed for an ISI of 1 second. CONCLUSION: This is the first fMRI study investigating the haemodynamic refractory effects in MwoA patients. Unlike in controls, these effects are not observed in migraineurs. Although currently unclear, it is tempting to speculate that this observation reflects the neurovascular correlate of lack of habituation measured with evoked potentials in migraineurs.

Does visual cortex lactate increase following photic stimulation in migraine without aura patients? A functional (1)H-MRS study.

Proton magnetic resonance spectroscopy ((1)H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS ((31)P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional (1)H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1-0.2 µmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients.

Neural correlates of pantomiming familiar and unfamiliar tools: action semantics versus mechanical problem solving?

This study aims to reveal the neural correlates of planning and executing tool use pantomimes and explores the brain's response to pantomiming the use of unfamiliar tools. Sixteen right-handed volunteers planned and executed pantomimes of equally graspable familiar and unfamiliar tools while undergoing fMRI. During the planning of these pantomimes, we found bilateral temporo-occipital and predominantly left hemispheric frontal and parietal activation. The execution of the pantomimes produced additional activation in frontal and sensorimotor regions. In the left posterior parietal region both familiar and unfamiliar tool pantomimes elicit peak activity in the anterior portion of the lateral bank of the intraparietal sulcus--A region associated with the representation of action goals. The cerebral activation during these pantomimes is remarkably similar for familiar and unfamiliar tools, and direct comparisons revealed only few differences. First, the left cuneus is significantly active during the planning of pantomimes of unfamiliar tools, reflecting increased visual processing of the novel objects. Second, executing (but not planning) familiar tool pantomimes showed significant activation on the convex portion of the inferior parietal lobule, a region believed to serve as a repository for skilled object-related gestures. Given the striking similarity in brain activation while pantomiming familiar and unfamiliar tools, we argue that normal subjects use both action semantics and function from structure inferences simultaneously and interactively to give rise to flexible object-to-goal directed behavior.

Differentiation between deep and superficial fibers of the lumbar multifidus by magnetic resonance imaging.

The purpose of this study was to investigate the differentiation in muscle tissue characteristics and recruitment between the deep and superficial multifidus muscle by magnetic resonance imaging. The multifidus is a very complex muscle in which a superficial and deep component can be differentiated from an anatomical, biomechanical, histological and neuromotorial point of view. To date, the histological evidence is limited to low back pain patients undergoing surgery and cadavers. The multifidus muscles of 15 healthy subjects were investigated with muscle functional MRI. Images were taken under three different conditions: (1) rest, (2) activity without pain and (3) activity after experimentally induced low back muscle pain. The T2 relaxation time in rest and the shift in T2 relaxation time after activity were compared for the deep and superficial samples of the multifidus. At rest, the T2 relaxation time of the deep portion was significantly higher compared to the superficial portion. Following exercise, there was no significant difference in shift in T2 relaxation time between the deep and superficial portions, and in the pain or in the non-pain condition. In conclusion, this study demonstrates a higher T2 relaxation time in the deep portion, which supports the current assumption that the deep multifidus has a higher percentage of slow twitch fibers compared to the superficial multifidus. No differential recruitment has been found following trunk extension with and without pain induction. For further research, it would be interesting to investigate a clinical LBP population, using this non-invasive muscle functional MRI approach.

Tool responsive regions in the posterior parietal cortex: effect of differences in motor goal and target object during imagined transitive movements.

Neuroanatomical and functional studies have proposed a functional segregation of the human dorsal stream into a dorso-dorsal pathway, believed to serve as an object-independent stream involved with on-line control of action, and a ventro-dorsal pathway that provides conceptual input guiding the functional manipulation of objects. We aim to evaluate whether the inferior parietal cortex deals specifically with action reliant on stored knowledge. Fifteen right-handed, normal volunteers varied the intention of their transitive movements by imagining their dominant arm and hand pointing to, grasping to move, grasping to use, or grasping and using three-dimensional representations of target objects depicting graspable neutral shapes, unfamiliar tools, and familiar tools. Imagined movements intended to make functional use of familiar objects revealed increased activation in the left inferior parietal lobule. Compared to gestures aimed at displacing an object, functional (use) intentions elicited activation in the anterior and middle portions of the lateral bank of the intraparietal sulcus, suggesting involvement in the higher order control of action. Compared to functionally unfamiliar objects, grasping movements aimed at familiar tools activated the convex portion of the inferior parietal lobule, suggesting a role for the ventro-dorsal stream in object-selectivity. These data confirm that stored knowledge for the skillful manipulation of familiar tools of right-handed volunteers is predominantly located in the left inferior parietal lobule, and further suggest that tool use-responsive regions and tool object-responsive regions are not identical, but may form a local network in which different nodes contribute differently to the representation of functional tool use in humans.