Abstract

Ideational apraxia is characterized by impaired knowledge of action concepts and proper object usage. The present functional magnetic resonance imaging study aimed at investigating the neural system underlying conceptual knowledge for proper object use in healthy subjects, when the effects of visuospatial properties and perceptual modality were taken into account. Subjects performed semantic decision tasks requiring retrieval of knowledge about either object functional purposes (functional task) or visuospatial object properties (visuospatial task) and perceptual control tasks. The semantic tasks were performed with pairs of either written object names or object drawings. Activation for the functional task in common for words and pictures, compared with the visuospatial and control tasks, was found in left parietal–temporal–occipital (PTO) junction, inferior frontal, anterior dorsal premotor, and presupplementary motor areas. Ventral inferior frontal cortex activation correlated negatively with reaction time in the functional condition. No specific activation characterized the visuospatial task compared with the functional task. The conceptual tasks, compared with the control tasks, demonstrated overlapping activation in left PTO junction, prefrontal, dorsal premotor, cuneus, and inferior temporal areas. These results outline the neural processes underlying conceptual knowledge for proper object use. The left ventral inferior frontal gyrus might facilitate behavioral decisions regarding functional/pragmatical object properties.

Introduction

Human object use involves conceptual knowledge of objects acted upon as well as action skills. Neuropsychological and neuroimaging evidence indicates that these aspects are represented by functionally specialized neural systems (Hodges et al. 1999; Johnson-Frey 2004). Information about a neural system for conceptual knowledge of proper object use is provided by patients with ideational apraxia (IA). IA patients are characterized by impaired knowledge of action intentions/concepts and proper object usage (Pick 1905; Morlaas 1928; De Renzi and Lucchelli 1988). In contrast, motor skills for dexterous performance are preserved (De Renzi and Lucchelli 1988; Johnson-Frey 2004). As a consequence, IA patients can attempt to brush their teeth with a comb and eat with a toothbrush, even when able to name and handle the objects properly (Ochipa et al. 1989). Accordingly, IA symptomatology is also reported in semantic dementia, a disorder with disrupted knowledge of object meaning and facts (Hodges et al. 2000). IA results principally from lesions in the left hemisphere (LH), most frequently reported at the parietal–temporal–occipital (PTO) junction, but often extending to surrounding and frontal areas (Liepmann 1920; De Renzi and Lucchelli 1988).

Functional neuroimaging studies in normal subjects have provided further insight in the neural representation of object-related action concepts. These studies focused mainly on the neural representation of knowledge about specific object-related actions and tools intrinsically related to human pragmatic acts (Thompson-Schill 2003). Viewing tools, naming tools, answering questions about tools, generating verbs to tools, identifying actions associated with tools activated a distributed network of areas in the LH, comprising posterior middle temporal gyrus (MTG), inferior frontal cortex, middle frontal gyrus, dorsal and ventral premotor area, cerebellum, medial fusiform gyrus, and anterior intraparietal cortex (Martin et al. 1995; Perani et al. 1995; Martin et al. 1996; Grafton et al. 1997; Tranel et al. 1997; Grabowski et al. 1998; Chao et al. 1999; Perani et al. 1999; Chao and Martin 2000; Damasio et al. 2001; Phillips et al. 2002; Noppeney et al. 2006; see for reviews: Martin and Chao 2001; Johnson-Frey 2004). In contrast to what lesion studies in patients with IA would suggest (Liepmann 1920; De Renzi and Lucchelli 1988), neither the functional imaging studies mentioned above nor a lesion analysis study (Tranel et al. 2003) showed involvement of the left PTO junction (Brodmann area [BA] 39) in knowledge about object-related actions. However, to our knowledge, no previous functional neuroimaging studies investigated specifically conceptual knowledge of proper object use, that is, the functional/pragmatic purposes of objects, as principally impaired in IA. The distinction between knowledge of object-related actions and functional/pragmatic purposes of objects is relevant, because knowledge about object-related actions only (for instance, striking or pouring) is not sufficient to use an object (match or bottle) successfully for the correct purpose (light a candle or fill a glass) (see, e.g., De Renzi and Lucchelli 1988). The left PTO junction might be of particular importance for knowledge of functional/pragmatic object purposes by accessing and integrating object concepts for proper usage.

The present functional magnetic resonance imaging (fMRI) study aimed at investigating the neural system underlying conceptual knowledge for proper object use (functional/pragmatic object properties) in healthy subjects. A major issue of debate in cognitive neuroscience is whether the aforementioned cortical regions constitute distinct neural stores for different aspects of conceptual knowledge, like object properties (Warrington and Shallice 1984; Martin et al. 2000) or categories (Caramazza and Shelton 1998), or whether a distinction is an emergent property of the structure and content of semantic representations in a distributed neural network (Tyler et al. 2000; Tyler and Moss 2001). It is an open issue whether a neural system for action semantics is differentiated for functional/pragmatical and visuospatial object properties or to which degree there is automatic activation of object visuospatial and functional/pragmatic properties when an object concept is evoked. Knowledge about visuospatial object properties, for example, assessed by means of visual imagery of objects compared with perception, is suggested to be represented in a network comprising dorsal occipital, extrastriate, posterior inferior and lateral temporal, premotor, cerebellum, and prefrontal regions, predominantly, in the LH but sometimes also in homologeous right hemisphere regions (D'Esposito et al. 1997; Mellet et al. 1998; Ishai et al. 2000; Phillips et al. 2002; Yomogida et al. 2004).

A related question is whether conceptual knowledge for proper object use parallels areas representing action skills, like premotor and inferior parietal areas, because knowledge about the functional/pragmatic object properties might be acquired through active object use, and its retrieval might require mental simulation (Warrington and McCarthy 1987; Martin et al. 2000; Johnson-Frey 2004; Gallese and Lakoff 2005).

For this purpose, subjects performed semantic decision tasks requiring retrieval of knowledge about either functional/pragmatical (functional task) or visuospatial object properties (visuospatial task) and perceptual control tasks. The semantic tasks were performed with pairs of either written object names or object drawings. This experimental design allowed us to differentiate between knowledge about the visuospatial and functional/pragmatical object properties, the latter being the focus of our study, while controlling for the effects of perceptual processes and modality-specific activation.

Methods

Subjects

Seventeen young adult university students were included in the present analyses, out of which 16 were males and 1 female (mean age = 21.7 years). Three subjects were excluded from participation to the experiment for medical or practical reasons. All subjects were right-handed (Edinburgh Handedness Inventory score > 0.85), native Italian speakers (without other native languages) with normal vision capabilities (correction < 0.75). Written informed consent was obtained from all subjects after full explanation of the aim and procedure of the study, in line with the Declaration of Helsinki. The experimental protocol was approved by the local institutional ethics committee. The subjects were recruited from a list of students who declared previously to be available to participate on a voluntary basis in an fMRI experiment.

Stimuli

Visual stimuli were drawings or (Italian) words, representing objects chosen from the International Picture Naming Project (Bates et al. 2003; http://crl.ucsd.edu/∼aszekely/ipnp/). Two lists of object pairs were composed, one for each semantic condition (functional and visuospatial). Both lists exactly contained the same single objects. The arrangement of the pairs was different between the “functional” and “visuospatial” condition to compose unambiguous pairs with respect to association or relative size. The same object pairs were used for the word and drawing versions of the semantic tasks. In a pair, one drawing or word was presented beneath and one above a central fixation cross.

In the functional condition, the objects were functionally related through an aimed human action in half of the pairs, whereas they were unrelated in the other half. In the visuospatial condition, the lowest object was bigger than the upper (in real-life size) in half of the pairs, and the opposite was true in the other half. Visual cues regarding real-life size were minimized.

Prior to the fMRI experiment, all the individual words and pictures and the whole set of 480 pairs of the mentioned items were validated by 10 healthy subjects with respect to their functional association, (relative) size, meaning, and reaction time. Subsequently, 224 clear and unambiguous pairs were selected for the final tasks (>90% correct responses).

During fMRI scanning, the functional condition consisted of a sequence of 28 pairs of objects that were functionally related through an aimed action and 28 pairs with objects that were functionally unrelated. The visuospatial condition contained a sequence of 28 pairs with the lowest object bigger in real-life size and 28 pairs with the lower object smaller in real-life size.

In addition, a sequence of 56 pairs of meaningless drawings and a sequence of 56 pairs of pronounceable pseudowords were added as control conditions. The drawings or pseudowords were identical in 28 pairs and different in the other 28 pairs. The pseudowords matched the real words for number of letters.

Figure 1 shows examples of the stimuli used in the present study.

Figure 1.

Examples of the stimuli used in the study.

Figure 1.

Examples of the stimuli used in the study.

Conditions and Tasks

The experiment comprised 12 conditions in a 2 × 2 × 3 factorial design. The first factor was stimulus type (drawings of objects and written object names) to control for the effects of perceptual modality because there might be modality-specific activation related to the perception of object pictures or words, although there is a shared conceptual system for both (Vandenberghe et al. 1996; Sevostianov et al. 2002; Bright et al. 2004; Gates and Yoon 2005). The second factor was response hand (right hand and left hand). This factor allowed the control of lateralization and interaction/facilitation effects related to the subjects' response to the task, instead of conceptual content. These effects might occur due to the use of only the right or left hand for the motor response. Indeed, functional knowledge is considered as a LH function, whereas visuospatial knowledge has been associated also with right hemisphere functioning. Moreover, premotor areas might contribute to conceptual processing too. The third factor was task (functional, visuospatial, and control). The functional task required subjects to judge the functional/pragmatical properties of objects. The subjects were asked whether 2 simultaneously presented objects (e.g., broom–dustpan) could be functionally associated through an aimed human action, that is, used together for a meaningful purpose. In the visuospatial task, subjects judged the visuospatial characteristics of the objects. Subjects were asked whether the lowest of 2 objects (e.g., cup–rake) was bigger in real life than the upper. The control tasks implied the evaluation of the perceptual properties of meaningless words or drawings. The subjects responded whether 2 pseudowords or meaningless drawings were identical or not.

In all the 3 tasks (functional, visuospatial, and control), subjects were required to press one of 2 buttons as accurately as possible in the first place, but also as fast as possible, with their index finger to respond “yes” and with their middle finger to respond “no”. Subjects responded with their right hand during half of the trials and with their left hand during the other half.

Procedure

All subjects completed all 12 conditions. The order of the conditions was pseudorandomized for each subject. Trials requiring “yes” and “no” responses were randomized during each condition.

Immediately prior to scanning, subjects were required to read the names and watch the corresponding drawings of all individual objects in order to minimize the effects of priming and of difficulties in the recognition of the object drawings during fMRI scanning. To habituate the subjects to the experimental tasks, all 12 conditions were practiced prior to scanning with object pairs “different” from those presented during scanning.

The experimental paradigm was a block design alternating a state of stimulation of 22.05 s with a control state having the same duration. Each stimulation block consisted of 7 trials, with a trial duration of 3000 ms and an intertrial interval of 150 ms. During each condition 28 pairs were visually presented. The fixation cross was also present during the rest intervals. Each condition started with a rest state before presentation of the pairs. Figure 2 demonstrates the temporal course of stimulus presentation and rest blocks during each condition.

Figure 2.

Temporal course of rest and stimulus presentation blocks during one condition.

Figure 2.

Temporal course of rest and stimulus presentation blocks during one condition.

The stimuli were presented on a screen behind the scanner with a beamer. The subject could see the screen clearly through a mirror placed above the eyes.

Data Acquisition

For each subject, blood oxygen level–dependent (BOLD) contrast functional imaging was performed with a Siemens Magnetom Vision scanner at the Institute of Advanced Biomedical Technologies (Chieti) at 1.5T by T2*-weighted echo planar imaging free induction decay sequences with the following parameters: time repitition (TR) 3150 ms, echo time (TE) 60 ms, matrix size 64 × 64, field of view (FOV) 256 mm, in-plane voxel size 4 × 4 mm, flip angle 90°, slice thickness 4 mm and no gap. A standard head coil was used and the subject's head was fixed with foam pads to reduce involuntary movement. Functional volumes consisted of 28 transaxial slices. For each run, 56 volumes were acquired, with 7 volumes per block.

A high-resolution structural volume was acquired at the end of the session via a 3D MPRAGE sequence with the following features: sagittal, matrix 256 × 256, FoV 256 mm, slice thickness 1 mm, no gap, in-plane voxel size 1 × 1 mm, flip angle 12°, TR = 9.7 ms, TE = 4 ms.

Data Analyses and Statistical Contrasts

Raw data were analyzed with the Brain Voyager QX software (Brain Innovation, Maastricht, The Netherlands). Due to T1 saturation effects, the first 3 scans of each run were discarded from the analysis. Preprocessing of functional data included motion correction and removal of linear trends from voxel time series. A 3-dimensional (3D) motion correction was performed with a rigid-body transformation to match each functional volume to the reference volume (the fourth volume) estimating 3 translation and 3 rotation parameters. Preprocessed functional volumes of a subject were coregistered with the corresponding structural data set. As the 2D functional and 3D structural measurements were acquired in the same session, the coregistration transformation was determined using the Siemens slice position parameters of the functional images and the position parameters of the structural volume.

Structural and functional volumes were transformed into the Talairach space (Talairach and Tournoux 1998) using a piecewise affine and continuous transformation. Functional volumes were resampled at a voxel size of 3 × 3 × 3 mm. Statistical analysis was performed using the general linear model (GLM) (Friston et al. 1995). To account for the hemodynamic delay, the boxcar waveform representing the rest and task conditions was convolved with an empirically based hemodynamic response function (Boynton et al. 1996). To search for activated areas that were consistent for the whole group of subjects, a statistical group analysis was performed. In this case, the time series from each run and subject were z normalized and concatenated before the GLM computation. No spatial or temporal smoothing was performed in this analysis.

The group statistical maps obtained through the different contrasts described below were thresholded at P < 0.05, corrected for multiple comparisons using the false discovery rate (Genovese et al. 2003).

For all experimental conditions, the left- and right-handed runs were grouped together. For all contrasts, conjunction analyses (Price and Friston 1997; Nichols et al. 2005) between word and picture conditions were performed. Conjunction analyses were applied to separate effects of different structural analyses required by the perception of either words or pictures (perceptual modality) and, hence, to focalize specifically on their shared semantic component.

In first-level contrasts, the functional and the visuospatial conditions were contrasted separately with the control condition. By means of these first-level contrasts, the areas specifically involved in conceptual knowledge of functional objects (in which we were especially interested) could be identified, while the effects of perceptual processes were taken into account. Because different aspects (e.g., functional/pragmatic and visuospatial) of object knowledge can be activated automatically when an object concept is evoked by a word or picture (Martin et al. 2000; Tyler et al. 2003), the control condition contained meaningless stimuli to prevent exclusion of relevant brain areas by contrasting the conceptual tasks with the control task. Subsequently, in second-level analyses, the functional and visuospatial conditions were contrasted to emphasize the areas involved in different aspects of conceptual object knowledge (i.e., functional/pragmatical and visuospatial) for the voxels that were found to be relevant for conceptual processing as revealed by the first-level contrast with the corresponding conceptual task (functional vs. control or visuospatial vs. control). Inclusive masking in order to define regions of interest (ROIs) has been applied in previous functional neuroimaging studies regarding the conceptual system (e.g., Vandenberghe et al. 1996; Phillips et al. 2002; Chao et al. 2002). The inclusive masks obtained by the first-level contrasts allowed to focus on the differentiation within the conceptual system for functional objects and ensured that specific activation for different semantic properties was also significantly increased in comparison with the perceptual control condition (i.e., to control for false-positive effects).

To ensure that differences in activation between the semantic conditions were consistent across subjects, random-effect analyses were performed on the ROIs obtained by the specific second-level contrasts. In these analyses, the invidual subject's responses to the different conditions were characterized by evaluating the relative signal variation (BOLD signal percentage change) between baseline (rest) and experimental condition in each ROI. Statistical significance was assessed by means of paired t-tests.

To determine the overlapping activation between the functional and visuospatial semantic tasks, conjunction analyses were performed between all the semantic tasks (words/functional, words/visuospatial, pictures/functional, pictures/visuospatial) compared with the control condition.

Finally, to investigate the relationship between specific activation for the semantic tasks and task performance, correlations were computed between BOLD responses for the different conditions in the specified ROIs and mean reaction times in the corresponding conditions.

Results

Behavioral Results

Mean reaction time across all conditions was 1201 ms (standard deviation = 442). With respect to the single conditions, reaction time was 1367 ms for the visuospatial task, 1240 ms for the functional task, and 1000 ms for the control task. Analyses of variance showed statistically significant differences (F =150.549, P < 0.001). Post hoc comparisons with Bonferroni corrections showed that reaction time was longer in the visuospatial condition than in the functional condition (P < 0.001) and longer in the functional condition than in the control condition (P < 0.001). Overall subject responses were correct in 93.9% of the trials. The response accuracy differed significantly between the visuospatial and the functional task (P < 0.01) and between the visuospatial and the control task (P < 0.01) but not between the functional and control condition. The response accuracy was 95% in the functional task, 90.1% in the visuospatial task, and 96.4% in the control task.

fMRI Results

Compared with the control condition (conjunction between the contrasts: functional/pictures vs. control/pictures and functional/words vs. control/words), the functional condition elicited significantly more activation in LH lateral temporal cortex (BA 21/37), PTO junction (BA 39/19), inferior frontal cortex (BA 45/47), medial inferior temporal cortex, dorsal premotor cortex (BA 6), presupplementary motor area, middle frontal gyrus (BA 9/46), medial frontal cortex (BA 6/8/9), cuneus, and posterior cingulate. The visuospatial task (conjunction between the contrasts: visuospatial/pictures vs. control/pictures, and visuospatial/words vs. control/words) showed significantly more activation in bilateral PTO junction (BA 39/19), LH dorsal premotor cortex (BA 6), middle frontal gyrus (BA 9), and cuneus compared with the control condition.

Conjunction analyses among all semantic conditions, compared with the control condition (conjunction between the contrasts: functional/pictures vs. control/pictures, functional/words vs. control/words, visuospatial/pictures vs. control/pictures, and visuospatial/words vs. control/words), demonstrated overlapping activation (P < 0.05 corrected) for the semantic tasks in LH PTO junction (BA 39/19), middle frontal gyrus (BA 9), medial inferior temporal cortex, and cuneus. Overlapping semantic activation is shown in Figure 3 (in blue). Table 1 shows statistical values and coordinates in Talairach space (Supplementary Fig. 1 demonstrates BOLD signal percentage change during the different conditions in the overlapping areas).

Figure 3.

Activation patterns obtained by group analyses projected on a flattened surface of a single subject brain (yellow: specific activation for the functional condition, compared with the visuospatial and control condition; blue: overlapping activation for the functional and visuospatial condition, compared with the control condition).

Figure 3.

Activation patterns obtained by group analyses projected on a flattened surface of a single subject brain (yellow: specific activation for the functional condition, compared with the visuospatial and control condition; blue: overlapping activation for the functional and visuospatial condition, compared with the control condition).

Table 1

Statistical values and coordinates for the activation obtained by the different statistical contrasts

Localization Hemisphere BA Peak t value (df = 10835) Significance Talairach coordinates (x, y, z
Specific activation for the functional task compared with the visuospatial task 
    PTO Left 39 4.186495 P < 0.0001 −40,–64, 25 
    PTO Left 19/39 4.432064 P < 0.00001 −48, –64, 13 
    Inferior frontal gyrus Left 47 3.730966 P < 0.001 −43, 27, −2 
    Inferior frontal gyrus Left 47 3.678535 P < 0.001 −43, 36, −2 
    Presupplementary motor area Left 3.997654 P < 0.0001 −3, 15, 52 
    Anterior dorsal premotor cortex Left 3.950612 P < 0.0001 −30, 6, 46 
Overlapping activation for the functional and visuospatial task compared with the control task 
    PTO Left 39 5.544916 P < 0.000001 −32, −62, 30 
    Middle frontal gyrus Left 9/46 5.365037 P < 0.000001 −49, 23, 26 
    Dorsal premotor cortex Left 4.217449 P < 0.0001 −30, 4, 54 
    Cuneus Left — 4.973810 P < 0.0001 −6, −67, 25 
    Medial temporal cortex Left — 4.101119 P < 0.0001 −33, −34, −11 
Localization Hemisphere BA Peak t value (df = 10835) Significance Talairach coordinates (x, y, z
Specific activation for the functional task compared with the visuospatial task 
    PTO Left 39 4.186495 P < 0.0001 −40,–64, 25 
    PTO Left 19/39 4.432064 P < 0.00001 −48, –64, 13 
    Inferior frontal gyrus Left 47 3.730966 P < 0.001 −43, 27, −2 
    Inferior frontal gyrus Left 47 3.678535 P < 0.001 −43, 36, −2 
    Presupplementary motor area Left 3.997654 P < 0.0001 −3, 15, 52 
    Anterior dorsal premotor cortex Left 3.950612 P < 0.0001 −30, 6, 46 
Overlapping activation for the functional and visuospatial task compared with the control task 
    PTO Left 39 5.544916 P < 0.000001 −32, −62, 30 
    Middle frontal gyrus Left 9/46 5.365037 P < 0.000001 −49, 23, 26 
    Dorsal premotor cortex Left 4.217449 P < 0.0001 −30, 4, 54 
    Cuneus Left — 4.973810 P < 0.0001 −6, −67, 25 
    Medial temporal cortex Left — 4.101119 P < 0.0001 −33, −34, −11 

The contrast between the functional and visuospatial task (conjunction between the contrasts: functional/pictures vs. visuospatial/pictures and functional/words vs. visuospatial/words) revealed specific statistical activation (P < 0.05 corrected) for the functional task in LH PTO junction (BA 39/19), anterior dorsal premotor cortex (BA 6), presupplementary motor area (BA6), and inferior frontal cortex (BA 47). Random-effect analyses applied to the ROIs confirmed that this activation was consistent across subjects (P < 0.05). Activation specific for the functional condition is shown in Figure 3 (in yellow). Table 1 shows the statistical values and coordinates in Talairach space (Supplementary Fig. 2 demonstrates BOLD signal percentage change during the different conditions in the functional specific areas). No significant activation was found for the visuospatial condition compared with the functional condition (conjunction between the contrasts: visuospatial/pictures vs. functional/pictures and visuospatial/words vs. functional/words).

To control for the possibility that activation could be attributed to differences in task difficulty or mental load between the conditions (as reflected by different reaction times), covariance analyses were performed on the ROIs obtained by the contrasts between the conditions with reaction time as covariate. Covariance analyses demonstrated consistent significance of BOLD response differences between the conditions in the ROIs (P < 0.01). Furthermore, covariance analyses failed to detect significant effects of the covariate reaction time, except in the left inferior frontal cortex (P < 0.01). Nevertheless, the effect of condition (functional minus visuospatial) remained significant in left inferior frontal cortex.

Correlation between fMRI and Reaction Time

To investigate the relationship between subject responses and BOLD signal in the ROIs representing functional/pragmatical knowledge for object use (left BA 39, BA 6, and BA 47), correlations between these 2 values were calculated. Beta values for the ROIs showed a normal distribution, but this was not the case for reaction times. Therefore, the nonparametric Spearman test was applied to calculate the correlation. The only significant result (with Bonferroni correction) was a negative correlation in BA 47 (r = −0.33, P = 0.006). The stronger the activity in left BA 47, the shorter the reaction time to respond whether 2 objects were functionally related (see scatterplot in Fig. 4).

Figure 4.

Scatterplot for the correlation (r = −0.33, P < 0.01) between reaction times in the functional condition and BOLD response in the left inferior frontal cortex (BA 47).

Figure 4.

Scatterplot for the correlation (r = −0.33, P < 0.01) between reaction times in the functional condition and BOLD response in the left inferior frontal cortex (BA 47).

The above mentioned correlation raised the question whether the activation of the left inferior frontal cortex increased with the level of mental load or difficulty of performance in the functional task (e.g., due to incongruity of the functionally unrelated object pairs). To address this issue, the reaction times of the related and unrelated pairs were compared. Mean reaction time was significantly longer (F = 55.881, P < 0.001) for the unrelated pairs (1304 ms) than for the related pairs (1168 ms).

Discussion

The aim of the present fMRI study was to investigate the neural processes underlying functional/pragmatical knowledge for proper object usage in healthy subjects. The main methodological issues were to separate the visuospatial (task for knowledge of real-life object size) from the functional/pragmatical (task for knowledge of functional/pragmatical properties) aspects of conceptual object knowledge, the latter being the focus of our study, while the effects of perceptual modality (perceptual control task and conjunction analyses between words and pictures) were taken into account. The high response accuracy (>93%), indicated that subjects performed the tasks correctly and that the stimuli were unambiguous with respect to the tasks. Compared with the perceptual control task, analyses of fMRI data revealed a distributed network of areas in the LH for conceptual object processing, comprising temporal cortex (BA 21/37), PTO junction (BA 39/19), inferior frontal cortex (BA 45/47), medial inferior temporal cortex, dorsal premotor cortex, middle frontal gyrus (BA 9/46), medial frontal cortex (BA 6/8/9), posterior cingulate, and cuneus. This is largely in accordance with previous evidence from functional neuroimaging studies and lesion analyses related to action semantics (Martin and Chao 2001; Tranel et al. 2003; Johnson-Frey 2004). Compared with the visuospatial condition (retrieval of object real-life size), the functional condition (retrieval of object functional/pragmatical properties) induced enhanced activation in LH PTO junction (BA 39/19), anterior portion of dorsal premotor cortex, presupplementary motor area, and inferior frontal cortex (BA 47). From a topographic perspective, activation in the functional and visuospatial conditions overlapped in the LH PTO junction (BA 39/19), middle frontal gyrus (BA 9/46), dorsal premotor cortex, medial inferior temporal cortex, and cuneus. In contrast, the activation of the left inferior frontal cortex was observed only in the functional condition. These results are in accordance with the localization of lesions in IA patients (Liepmann 1920; De Renzi and Lucchelli 1988).

The results of the present study clarify several aspects of the neural processes underlying knowledge about functional/pragmatical object properties. The first aspect regards the role of the left PTO junction (BA 39/19). The left PTO junction is a multimodal association area with more general functions in semantic processing, including mapping sensory/visual input into linguistic representations (Dejerine 1892; Damasio and Damasio 1983; Henderson 1986; Binder et al. 1997; Horwitz et al. 1998). Accordingly, aphasia is very common in IA patients (Keretz and Hooper 1982; De Renzi and Lucchelli 1988). Consistent with previous studies, the PTO junction was activated during semantic tasks regarding different object properties (Vandenberghe et al. 1996), possibly integrating information from multiple domains within a general conceptual system. However, as suggested by increased activation during the functional task in the present study, knowledge about proper object use could rely more heavily on its multimodal association properties than knowledge of visuospatial characteristics. Indeed, objects are not used in isolation, but in a strict relationship with other objects through specific motor acts to complete an action succesfully in context. For instance, one hits a nail with a hammer, but not a match; one eats from a plate with a dinner fork, but not with a toothbrush. In this sense, the present results update the common view that the left PTO junction is mainly involved in general semantic processing in terms of linguistic code (Price 2000). Furthermore, they confirm previous findings indicating that IA patients suffer from lesions in the left PTO junction and might offer an explanation for the high prevalence of aphasia in IA (Liepmann 1920; Keretz and Hooper 1982; De Renzi and Lucchelli 1988).

The second aspect concerns the role of the left anterior dorsal premotor cortex and presupplementary motor area for object conceptual/functional knowledge. Activation in these areas might underlie cognitive aspects of motor processing, such as motor imagery and sensorimotor associations (Gerardin et al. 2000; Picard and Strick 2001; Johnson et al. 2002). These aspects would facilitate mental object manipulation at the basis of object-related action understanding. There was significant overlap in left dorsal premotor cortex for the visuospatial and functional condition, thus suggesting that cognitive aspects of motor processing are activated automatically by recognition of objects. This supports the recent Neural Theory of Language posing that what an image or word means is the mental simulation that it evokes. Functional objects could have a meaning that includes the conscious or unconcious simulation of the use of that object (Feldman and Narayanan 2004; Gallese and Lakoff 2005). The enhanced activation of left anterior dorsal premotor cortex and presupplementary motor area in the functional condition would indicate more explicit simulation in the active retrieval of functional/pragmatical object knowledge. Because the activation of this area extended to the connected prefrontal cortex (Gerardin et al. 2000; Picard and Strick 2001), this activation could be mediated by top-down control processes from the prefrontal cortex (Miller 2000; Noppeney et al. 2006).

Finally, an aspect of particular interest concerns the role of the left ventral inferior frontal cortex for object conceptual/functional knowledge. The left inferior frontal cortex (BA 47) was activated exclusively for the functional condition. This area is known to be involved in executive and working memory processes during semantic tasks, like semantic retrieval, selection, and unification (Vandenberghe et al. 1996; Gabrieli et al. 1998; Mummery et al. 1998; Poldrack et al. 1999; Noppeney and Price 2002; Hagoort et al. 2004; Hagoort 2005). Such processes might be necessary to associate 2 objects (e.g., Vandenberghe et al. 1996). Noteworthy, previous studies showed increased activation for enhanced task difficulty (Demb et al. 1995; Poldrack et al. 1999; Gold and Buckner 2002). Therefore, one might merely ascribe the present specific activation of this cortical area in the functional condition to increased task difficulty. However, this was not the case for 2 reasons. First, reaction times were longer for the visuospatial task than for the functional task, indicating enhanced task difficulty for the visuospatial condition. Second, correlation analyses showed a significant “negative” correlation between reaction times and activation in left inferior frontal cortex during the functional task. The stronger the activity in left inferior frontal cortex, the shorter the reaction time. Rather, the present results suggest an important role of this area in facilitating behavioral decisions regarding functional object properties, for example, whether the combination of 2 objects is appropriate to perform an action. Indeed, the significantly shorter reaction time for the functionally related pairs than for the unrelated pairs supports this hypothesis, although indirectly, given that due to the block design the related and unrelated pairs could not be analyzed separately. It can be speculated that the left inferior frontal cortex (BA 47) is involved in the conversion of functional object knowledge into actions. Enhanced activity might speed the sensorimotor information processing due to an increase of the local computational capacity. This view would explain why the increase of activation in BA 47 was associated with shorter reaction time in the present functional task and with the increase of computational task demands in previous studies.

No specific activity characterized the visuospatial condition in the conjunction analyses. This may be due to a strong automatic activation of visuospatial object features in both its observation and retrieval of functional properties (Martin et al. 2000; Tyler et al. 2003). Furthermore, the demands on the visual system in both the control condition and the functional task could have masked specific activity for the processing of the visuospatial object properties because knowledge about the visuospatial object characteristics might be represented partially in the corresponding modality (Barsalou et al. 2003; McClelland and Rogers 2003).

Some methodological remarks are in order. Semantic tasks were not matched for difficulty as reflected by longer reaction times and more errors for the visuospatial task than for the functional task. However, it is unlikely that cortical activation might reflect differences in task difficulty or mental load for 2 reasons. First, activation was found exclusively for the “easier” functional task. Second, covariance analyses with reaction time as covariate demonstrated consistent significance of differences in activation in the ROIs between the conditions. No significant effect of reaction time was found, except in the left inferior frontal cortex (indeed a significant correlation between reaction time and BOLD response was found in left inferior frontal cortex). Nevertheless, the condition effect remained significant in left inferior frontal cortex.

Furthermore, in contrast to previous studies, the present study did not demonstrate activation in putative canonical neurons areas related to the observation of tools and knowledge of object-related motor acts, like the ventral premotor cortex and intraparietal and posterior Middle Temporal (MT/V5) areas (Martin and Chao 2001; Rizzolatti et al. 2002; Grezes et al. 2003). A possible explanation could be that, instead of tool stimuli like used in most previous studies (see for reviews: Martin and Chao 2001; Johnson-Frey 2004), a set of man-made objects less strictly related to actions was used in the current study. Therefore, they might induce less simulation. Indeed, previous studies requiring semantic processing of man-made objects/artefacts other than tools did not report activation in canonical neuron areas (e.g., Mummery et al. 1998; Moore and Price 1999; Devlin et al. 2002). Moreover, subjects in the present study were not required to retrieve explicitly knowledge of object-related motor acts, but rather the functional purposes of objects, which is more abstract. However, another explanation could be that group analyses canceled activation because of intersubject variability. For instance, the localization of area MT is known to be variable across individuals and therefore difficult to detect by means of group analyses (Watson et al. 1993).

In conclusion, the results of the present fMRI study contribute to a better understanding of the cortical neural network representing conceptual/functional knowledge for proper object use in normal subjects. This network is distributed over the PTO junction, anterior portions of dorsal premotor cortex and presupplementary motor area, and anterior ventral inferior frontal cortex in the LH. Furthermore, it partially overlaps the network for knowledge about visuospatial characteristics in the medial inferior temporal cortex, left PTO junction, cuneus, dorsal premotor cortex, and middle frontal gyrus (dorsolateral prefrontal). These results suggest that specific activation for the retrieval of functional object properties, compared with visuospatial properties, reflects different demands (e.g., executive, associative, motor imagery) on a distributed multimodal semantic system. These demands might be related intrinsically to type of property and its retrieval. The specific contribution of each node of this circuit should be evaluated more in detail in future studies by transcranial magnetic stimulation in healthy subjects and patients with lesions in these regions and IA symptomatology.

With respect to IA, the present study could contribute to clarify the underlying mechanisms of this disorder, which is still a topic of discussion in cognitive neuroscience. IA symptoms are observed in temporal lobe atrophy patients with deteriorated object knowledge and recognition (semantic dementia; Hodges et al. 1999,2000). On the other hand, preserved object use has also been demonstrated in these patients (e.g., Snowden et al. 1996; Lauro-Grotto et al. 1997). To explain these contrasting findings, Hodges et al. (1999) proposed that sensory input (visual or tactile features) to a dorsal/parietal “how” system might trigger relatively appropriate object use without relying on object-specific knowledge in the ventral “what” system. However, IA can occur also in patients with both spared object knowledge and preserved object-specific action skills, excluding loss of object knowledge as a necessary condition for IA (e.g., De Renzi and Lucchelli 1988). Keeping in mind these data and considerations, the present results suggest that IA could occur due to the disruption of the cognitive processes involved in the retrieval and utilization of specific conceptual object knowledge for the proper performance of object-related actions, for example, due to lesions in the PTO junction. The left PTO junction could be of particular importance for the retrieval of object knowledge and its integration with action skills required for proper object usage. However, it should be noted that these cognitive processes for accessing and integrating conceptual content might not be specific for proper object use, but apply also to other functions with reference to conceptual object knowledge, like language, which is commonly impaired in cases of IA too.

Supplementary Material

Supplementary material can be found at: http://www.cercor.oxfordjournals.org/.

Conflict of Interest: None declared.

References

Barsalou
LW
Simmons
WK
Barbey
AK
Wilson
CD
Grounding conceptual knowledge in modality-specific systems
Trends Cogn Sci
 , 
2003
, vol. 
7
 (pg. 
84
-
91
)
Bates
E
D'Amico
S
Jacobsen
T
Szekely
A
Andonova
E
Devescovi
A
Herron
D
Lu
CC
Pechmann
T
Pleh
C
, et al.  . 
Timed picture naming in seven languages
Psychonom Bull Rev
 , 
2003
, vol. 
10
 (pg. 
344
-
380
)
Binder
JR
Frost
JA
Hammeke
TA
Cox
RW
Rao
SM
Prieto
T
Human brain language areas identified by functional magnetic resonance imaging
J Neurosci
 , 
1997
, vol. 
17
 (pg. 
353
-
362
)
Boynton
GM
Engel
SA
Glover
GH
Heeger
DJ
Linear systems analysis of functional magnetic resonance imaging in human V1
J Neurosci
 , 
1996
, vol. 
16
 (pg. 
4207
-
4241
)
Bright
P
Moss
H
Tyler
LK
Unitary vs. multiple semantics: PET studies of word and picture processing
Brain Lang
 , 
2004
, vol. 
89
 (pg. 
417
-
432
)
Caramazza
A
Shelton
JR
Domain-specific knowledge systems in the brain: the animate-inanimate distinction
J Cogn Neurosci
 , 
1998
, vol. 
10
 (pg. 
1
-
34
)
Chao
LL
Haxby
JV
Martin
A
Attribute-based neural substrates in temporal cortex for perceiving and knowing about objects
Nat Neurosci
 , 
1999
, vol. 
2
 (pg. 
913
-
919
)
Chao
LL
Martin
A
Representation of manipulable man-made objects in the dorsal stream
Neuroimage
 , 
2000
, vol. 
12
 (pg. 
478
-
484
)
Chao
LL
Weisberg
J
Martin
A
Experience-dependent modulation of category-related cortical activity
Cereb Cortex
 , 
2002
, vol. 
12
 (pg. 
545
-
551
)
Damasio
AR
Damasio
H
The anatomic basis of pure alexia
Neurology
 , 
1983
, vol. 
33
 (pg. 
1573
-
1583
)
Damasio
H
Grabowski
TJ
Tranel
D
Ponto
LL
Hichwa
RD
Damasio
AR
Neural correlates of naming actions and of naming spatial relations
Neuroimage
 , 
2001
, vol. 
13
 (pg. 
1053
-
1064
)
Dejerine
J
Contribution à l'étude anatomo-pathologique et clinique des différentes variétés de cécité verbale
Mém Soc Biol
 , 
1892
, vol. 
4
 (pg. 
61
-
90
)
Demb
JB
Desmond
JE
Wagner
AD
Vaidya
CJ
Glover
GH
Gabrieli
JD
Semantic encoding and retrieval in the left inferior prefrontal cortex: a functional MRI study of task difficulty and process specificity
J Neurosci
 , 
1995
, vol. 
15
 (pg. 
5870
-
5878
)
De Renzi
E
Lucchelli
F
Ideational apraxia
Brain
 , 
1988
, vol. 
111
 (pg. 
1173
-
1185
)
D'Esposito
M
Detre
JA
Aguirre
GK
Stallcup
M
Alsop
DC
Tippet
LJ
Farah
MJ
A functional MRI study of mental image generation
Neuropsychologia
 , 
1997
, vol. 
35
 (pg. 
725
-
730
)
Devlin
JT
Russell
RP
Davis
MH
Price
CJ
Moss
HE
Fadili
MJ
Tyler
LK
Is there an anatomical basis for category-specificity? Semantic memory studies in PET and fMRI
Neuropsychologia
 , 
2002
, vol. 
40
 (pg. 
54
-
75
)
Feldman
J
Narayanan
S
Embodied meaning in a neural theory of language
Brain Lang
 , 
2004
, vol. 
89
 (pg. 
385
-
392
)
Friston
KJ
Holmes
AP
Worsley
KJ
Poline
JP
Frith
CD
Frackowiak
RSJ
Statistical parametric maps in functional imaging: a general linear approach
Hum Brain Mapp
 , 
1995
, vol. 
2
 (pg. 
173
-
181
)
Gabrieli
JD
Poldrack
RA
Desmond
JE
The role of left prefrontal cortex in language and memory
Proc Natl Acad Sci USA
 , 
1998
, vol. 
95
 (pg. 
906
-
913
)
Gallese
V
Lakoff
G
The Brain's concepts: the role of the sensory-motor system in reason and language
Cogn Neuropsychol
 , 
2005
, vol. 
22
 (pg. 
455
-
479
)
Gates
L
Yoon
MG
Distinct and shared cortical regions of the human brain activated by pictorial depictions versus verbal descriptions: an fMRI study
Neuroimage
 , 
2005
, vol. 
24
 (pg. 
473
-
486
)
Genovese
CR
Lazar
NA
Nichols
T
Thresholding of statistical maps in functional neuroimaging using the false discovery rate
Neuroimage
 , 
2002
, vol. 
15
 (pg. 
870
-
878
)
Gerardin
E
Sirigu
A
Lehericy
S
Poline
JB
Gaymard
B
Marsault
C
Agid
Y
Le Bihan
D
Partially overlapping neural networks for real and imagined hand movements
Cereb Cortex
 , 
2000
, vol. 
10
 (pg. 
1093
-
1104
)
Gold
BT
Buckner
RL
Common prefrontal regions coactivate with dissociable posterior regions during controlled semantic and phonological tasks
Neuron
 , 
2002
, vol. 
35
 (pg. 
803
-
812
)
Grabowski
TJ
Damasio
H
Damasio
AR
Premotor and prefrontal correlates of category-related lexical retrieval
Neuroimage
 , 
1998
, vol. 
7
 (pg. 
232
-
243
)
Grafton
ST
Fadiga
L
Arbib
MA
Rizzolatti
G
Premotor cortex activation during observation and naming of familiar tools
Neuroimage
 , 
1997
, vol. 
6
 (pg. 
231
-
236
)
Grezes
J
Armony
JL
Rowe
J
Passingham
RE
Activations related to “mirror” and “canonical” neurones in the human brain: an fMRI study
Neuroimage
 , 
2003
, vol. 
18
 (pg. 
928
-
937
)
Hagoort
P
On Broca, brain, and binding: a new framework
Trends Cogn Sci
 , 
2005
, vol. 
9
 (pg. 
416
-
423
)
Hagoort
P
Hald
L
Bastiaansen
M
Petersson
KM
Integration of word meaning and world knowledge in language comprehension
Science
 , 
2004
, vol. 
304
 (pg. 
438
-
441
)
Henderson
VW
Anatomy of posterior pathways in reading: a reassessment
Brain Lang
 , 
1986
, vol. 
29
 (pg. 
119
-
133
)
Hodges
JR
Bozeat
S
Lambon Ralph
MA
Patterson
K
Spatt
J
The role of conceptual knowledge in object use: evidence from semantic dementia
Brain
 , 
2000
, vol. 
123
 (pg. 
1913
-
1925
)
Hodges
JR
Spatt
J
Patterson
K
“What” and “how”: evidence for the dissociation of object knowledge and mechanical problem-solving skills in the human brain
Proc Natl Acad Sci USA
 , 
1999
, vol. 
96
 (pg. 
9444
-
9448
)
Horwitz
B
Rumsey
JM
Donohue
BC
Functional connectivity of the angular gyrus in normal reading and dyslexia
Proc Natl Acad Sci USA
 , 
1998
, vol. 
95
 (pg. 
8939
-
8944
)
Ishai
A
Ungerleider
LG
Haxby
JV
Distributed neural systems for the generation of visual images
Neuron
 , 
2000
, vol. 
28
 (pg. 
979
-
990
)
Johnson
SH
Rotte
M
Grafton
ST
Hinrichs
H
Gazzaniga
MS
Heinze
HJ
Selective activation of a parietofrontal circuit during implicitly imagined prehension
Neuroimage
 , 
2002
, vol. 
17
 (pg. 
1693
-
1704
)
Johnson-Frey
SH
The neural bases of complex tool use in humans
Trends Cogn Sci
 , 
2004
, vol. 
8
 (pg. 
71
-
78
)
Keretz
A
Hooper
P
Praxis and language: the extent and variety of apraxia in aphasia
Neuropychologia
 , 
1982
, vol. 
20
 (pg. 
275
-
286
)
Lauro-Grotto
R
Piccini
C
Shallice
T
Modality-specific operations in semantic dementia
Cortex
 , 
1997
, vol. 
33
 (pg. 
593
-
622
)
Liepmann
HM
Die linke hemisphare und das handeln
Muench Med Wochenschr
 , 
1920
, vol. 
49
 (pg. 
2322
-
2326
2375–2378
Martin
A
Chao
LL
Semantic memory and the brain: structure and processes
Curr Opin Neurobiol
 , 
2001
, vol. 
11
 (pg. 
194
-
201
)
Martin
A
Haxby
JV
Lalonde
FM
Wiggs
CL
Ungerleider
LG
Discrete cortical regions associated with knowledge of color and knowledge of action
Science
 , 
1995
, vol. 
270
 (pg. 
102
-
105
)
Martin
A
Ungerleider
LG
Haxby
J
Gazzaniga
MS
Category-specificity and the brain: the sensory-motor model of semantic representations of objects
The cognitive neurosciences
 , 
2000
Cambridge (MA)
MIT press
(pg. 
1023
-
1036
)
Martin
A
Wiggs
CL
Ungerleider
LG
Haxby
JV
Neural correlates of category-specific knowledge
Nature
 , 
1996
, vol. 
379
 (pg. 
649
-
652
)
McClelland
JL
Rogers
TT
The parallel distributed processing approach to semantic cognition
Nat Rev Neurosci
 , 
2003
, vol. 
4
 (pg. 
310
-
322
)
Mellet
E
Tzourio
N
Denis
M
Mazoyer
B
Cortical anatomy of mental imagery of concrete nouns based on their dictionary definition
Neuroreport
 , 
1998
, vol. 
9
 (pg. 
803
-
808
)
Miller
EK
The prefrontal cortex and cognitive control
Nat Rev Neurosci
 , 
2000
, vol. 
1
 (pg. 
59
-
65
)
Moore
CJ
Price
CJ
A functional neuroimaging study of the variables that generate category-specific object processing differences
Brain
 , 
1999
, vol. 
122
 (pg. 
943
-
962
)
Morlaas
J
Contribution à l'Etude de l'Apraxie
1928
Paris
Legrand
Mummery
CJ
Patterson
K
Hodges
JR
Price
CJ
Functional neuroanatomy of the semantic system: divisible by what?
J Cogn Neurosci
 , 
1998
, vol. 
10
 (pg. 
766
-
777
)
Nichols
T
Brett
M
Andersson
J
Wager
T
Poline
JB
Valid conjuction inference with the minimum statistic
Neuroimage
 , 
2005
, vol. 
25
 (pg. 
653
-
660
)
Noppeney
U
Price
CJ
A PET study of stimulus- and task-induced semantic processing
Neuroimage
 , 
2002
, vol. 
15
 (pg. 
927
-
935
)
Noppeney
U
Price
CJ
Penny
WD
Friston
KJ
Two distinct neural mechanisms for category-selective responses
Cereb Cortex
 , 
2006
, vol. 
16
 (pg. 
437
-
445
)
Ochipa
C
Rothi
LJ
Heilman
KM
Ideational apraxia: a deficit in tool selection and use
Ann Neurol
 , 
1989
, vol. 
25
 (pg. 
190
-
193
)
Perani
D
Cappa
SF
Bettinardi
V
Bressi
S
Gorno-Tempini
M
Matarrese
M
Fazio
F
Different neural systems for the recognition of animals and man-made tools
Neuroreport
 , 
1995
, vol. 
6
 (pg. 
1637
-
1641
)
Perani
D
Schnur
T
Tettamanti
M
Gorno-Tempini
M
Cappa
SF
Fazio
F
Word and picture matching: a PET study of semantic category effects
Neuropsychologia
 , 
1999
, vol. 
37
 (pg. 
293
-
306
)
Phillips
JA
Noppeney
U
Humphreys
GW
Price
CJ
Can segregation within the semantic system account for category-specific deficits?
Brain
 , 
2002
, vol. 
125
 (pg. 
2067
-
2080
)
Picard
N
Strick
PL
Imaging the premotor areas
Curr Opin Neurobiol
 , 
2001
, vol. 
11
 (pg. 
663
-
672
)
Pick
A
Studiën über Motorische Apraxie und ihr Nahestehende Erscheinungen; ihre Bedeutung in der Symptomatologie Psychopathischer Symptomen-Komplexe
1905
Leipzig (Germany)
Deuticke
Poldrack
RA
Wagner
AD
Prull
MW
Desmond
JE
Glover
GH
Gabrieli
JD
Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex
Neuroimage
 , 
1999
, vol. 
10
 (pg. 
15
-
35
)
Price
CJ
The anatomy of language: contributions from functional neuroimaging
J Anat
 , 
2000
, vol. 
197
 (pg. 
335
-
359
)
Price
CJ
Friston
KJ
Cognitive conjunction: a new approach to brain activation experiments
Neuroimage
 , 
1997
, vol. 
5
 (pg. 
261
-
270
)
Rizzolatti
G
Fogassi
L
Gallese
V
Motor and cognitive functions of the ventral premotor cortex
Curr Opin Neurobiol
 , 
2002
, vol. 
12
 (pg. 
149
-
154
)
Sevostianov
A
Horwitz
B
Nechaev
V
Williams
R
Fromm
S
Braun
AR
fMRI study comparing names versus pictures of objects
Hum Brain Mapp
 , 
2002
, vol. 
16
 (pg. 
168
-
175
)
Snowden
JS
Griffiths
HL
Neary
D
Semantic-episodic memory interactions in semantic dementia; implications for retrograde memory function
Cogn Neuropsychol
 , 
1996
, vol. 
13
 (pg. 
1101
-
1137
)
Talairach
J
Tournoux
P
Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system—an approach to cerebral imaging
1988
New York (NY)
Thieme Medical Publishers
Thompson-Schill
SL
Neuroimaging studies of semantic memory: inferring “how” from “where”
Neuropsychologia
 , 
2003
, vol. 
41
 (pg. 
280
-
292
)
Tranel
D
Damasio
H
Damasio
AR
A neural basis for the retrieval of conceptual knowledge
Neuropsychologia
 , 
1997
, vol. 
35
 (pg. 
1319
-
1327
)
Tranel
D
Kemmerer
D
Damasio
H
Adolphs
R
Damasio
AR
Neural correlates of conceptual knowledge for actions
Cogn Neuropsychol
 , 
2003
, vol. 
20
 (pg. 
409
-
432
)
Tyler
LK
Moss
HE
Durrant-Peatfield
MR
Levy
JP
Conceptual structure and the structure of concepts: a distributed account of category-specific deficits
Brain Lang
 , 
2000
, vol. 
75
 (pg. 
195
-
231
)
Tyler
LK
Moss
HE
Towards a distributed account of conceptual knowledge
Trends Cogn Sci
 , 
2001
, vol. 
5
 (pg. 
244
-
252
)
Tyler
LK
Stamatakis
EA
Dick
E
Bright
P
Fletcher
P
Moss
H
Objects and their actions: evidence for a neurally distributed semantic system
Neuroimage
 , 
2003
, vol. 
18
 (pg. 
542
-
557
)
Vandenberghe
R
Price
C
Wise
R
Josephs
O
Frackowiak
RS
Functional anatomy of a common semantic system for words and pictures
Nature
 , 
1996
, vol. 
383
 (pg. 
254
-
256
)
Warrington
EK
McCarthy
RA
Categories of knowledge. Further fractionations and an attempted integration
Brain
 , 
1987
, vol. 
110
 (pg. 
1273
-
1296
)
Warrington
EK
Shallice
T
Category specific semantic impairments
Brain
 , 
1984
, vol. 
107
 (pg. 
829
-
854
)
Watson
JD
Myers
R
Frackowiak
RS
Hajnal
JV
Woods
RP
Mazziotta
JC
Shipp
S
Zeki
S
Area V5 of the human brain: evidence from a combined study using positron emission tomography and magnetic resonance imaging
Cereb Cortex
 , 
1993
, vol. 
3
 (pg. 
79
-
94
)
Yomogida
Y
Sugiura
M
Watanabe
J
Akitsuki
Y
Sassa
Y
Sato
T
Matsue
Y
Kawashima
R
Mental visual synthesis is originated in the fronto-temporal network of the left hemisphere
Cereb Cortex
 , 
2004
, vol. 
14
 (pg. 
1376
-
1383
)