The participants were 15 right-handed college students (7 females) aged between 19 and 41 years (mean=23.2±5.2). All were right-handed, native speakers of American English. Each participant gave signed informed consent approved by the Indiana University Institutional Review Board.

The experiment consisted of a practice session and a scanning session. In the practice session, participants were familiarized with the experiment and with the imaging environment. The experiment consisted of two conditions (object inspection and mental rotation) in which true/false statements were presented. For both the object inspection and mental rotation conditions the first noun phrase of the statements is a description of an object. However, for the object inspection condition more complex and detailed information was required. Another major difference between the two conditions is the verb phrase, or what participants are to do with the objects. In the object inspection condition (e.g., “The tip of a lizard’s tongue is shaped like the letter q.”) participants are expected to generate an image of the first object and compare it to the object described in the second noun phrase. On the other hand, in the mental rotation condition (e.g., “The capital letter h rotated 90 degrees is a capital i.”) participants are to manipulate (rotate) the first object and then compare it to the object described in the second noun phrase. The differences in processing occur at specific points in time which are expected to be observed in the fMRI time-course.

The stimuli used were piloted behaviorally. The pilot study consisted of a survey of 80 sentences. Participants were asked to state whether the sentences evoked a static visual image of an object (object inspection), a dynamic, or moving image of an object (mental rotation), or no image. They were then asked to rate how vivid the image generated was on a scale from 1-5 with 5 being extremely vivid. The sentences with a mean score of 3.5 or higher were used in the current imaging study; a total of forty sentences (20 for each condition) were selected. The mean number of words per sentence was similar for both conditions (object – 13.2; mental rotation – 13.5).

During scanning the sentences were presented on a screen located behind the participants and viewed via a mirror located on the head coil. Each sentence was presented for 8 seconds. Responses were collected using a fiber optic response device. The experiment was a slow, event-related design to ensure that the full hemodynamic response was accurately acquired. Each trial was separated by a 12-second rest period in which participants fixated on a plus sign in the center of the screen. The experiment consisted of two 8.75 min runs each run contained three 24-second fixation baseline periods.

The images were acquired on a 3T Siemen’s TRIO scanner with an 8-channel radio frequency coil located in the Imaging Research Facility at Indiana University. The functional images were acquired in 18 5mm thick oblique axial slices using the following parameters: TR=1000msec, TE=25 msec, flip angl=60^°, voxel size=3.125mm x 3.125mm x 5mm with a 1mm gap.

The data were analyzed using statistical parametric mapping (SPM2 from the Wellcome Department of Cognitive Neurology, London). Images were corrected for slice acquisition timing, resampled to 2 x 2 x 2 mm voxels Images were subsequently smoothed in the spatial domain with a Gaus-sian filter of 8 mm at full-width at half maximum. The data were also high-pass filtered with 1/128 Hz cutoff frequency to remove low-frequency signals (e.g., linear drifts). The images were motion-corrected and the motion parameters were incorporated in the design estimation. The EPI data were normalized to the Montreal Neurological Institute (MNI) EPI template. At the individual level, statistical analysis was performed on each participant’s data by using the general linear model and Gaussian random field theory as implemented in SPM2. Each event (trial) was convolved with a canonical hemodynamic response function and entered as regressors in the model [29].

For the random effects analysis on group data, one-sample t-tests were performed on contrast images (task versus fixation, static versus dynamic, and dynamic versus static) obtained from each individual analysis. Activated brain areas surviving FWE (family-wise error) correction with a threshold of p<0.05 and a cluster extent threshold of 6 voxels (∼ were one voxel in the original image space) were rendered on a template brain in SPM2. The MNI coordinates associated with the peak activation within a cluster were transformed to Talairach coordinates. Talairach Daemon (http://ric.uthscsa.edu/projects/talairachdaemon.html) was used to obtain the location (Brodmann’s area) of each cluster.

Finally, timecourse analysis was performed. Regions of interest (ROIs) were defined as spheres (radius=10 mm) with the center at the peak coordinates of the activation clusters obtained from the group composite maps. The MarsBar Matlab toolbox [30, http://marsbar.courceforge.net] was used to extract ROI data from each individual. Timecourses were collapsed across trials for each task condition for each participant and baseline corrected. An analysis of variance (ANOVA) was applied at each point in the timecourse to determine condition effects. A Bonferoni correction was applied to account for multiple comparisons.

Conjunction Analysis. A conjunction analysis was performed to determine the brain regions that were active during both conditions (see Fig. (1)). The regions that revealed significant overlap included: bilateral visual processing regions (both primary and secondary visual cortex) extending into the inferior temporal gyrus; a small region of the left BA7/40 of the parietal cortex; and a region of the left frontal cortex (BA6 extending inferiorly into BA44).

Fig. (1). The conjunction map that shows the common activation for object inspection and mental rotation.

Mental Rotation Minus Object Inspection. A number of cortical regions were found to be more involved during mental rotation compared to object inspection. These regions included those that have been implicated in spatial processing – bilateral parietal regions (inferior parietal and the in-traparietal sulcal regions), bilateral occipital/temporal regions, and the right prefrontal cortex – as well as the left premotor cortex (see Fig. ((2) and Table 1).

Fig. (2). The group map showing the mental rotation minus object inspection contrast on the left and the object inspection minus mental rotation contrast on the right.

Object Inspection Minus Mental Rotation. Although the mental rotation task was found to be more difficult than the object inspection task, based on the increase in reaction time, there were a number of cortical regions found to be more involved during object inspection compared to mental rotation. These regions included those that have been implicated in semantic processing – the inferior frontal cortex (BA 47) and the left superior frontal cortex – as well as the right cerebellum and the medial occipital cortex (lingual gyri), bilaterally (see Fig. ((2) and Table 1).

Timecourse Analysis. As expected, the two conditions activated a similar network of brain regions. However, the amount of activation within these regions was modulated by condition. This modulation can be seen easiest by examining the hemodynamic timecourse of activation. While there were a number of regions whose activation did not differentiate object inspection and mental rotation (e.g., early visual processing, regions of the inferior temporal cortex and a region of the right cerebellum, see Fig. (3)) there were others that did seem to activate more for one or the other condition. There were regions of the inferior temporal/occipital cortex, the medial superior extrastriate, the inferior frontal cortex, and the right cerebellum which revealed significantly more activation for the object compared to the mental rotation task (see Fig. (4)). Regions of the parietal cortex, inferior temporal/occipital cortex, and the prefrontal cortex revealed significantly more activation for the mental rotation compared to the object inspection condition (see Fig. (5)).

Fig. (3). The timecourse data from regions that revealed no condition differences. These regions were located within early visual processing regions. The coordinates indicate the location of the cluster centroid.

Fig. (4). The timecourse data from regions that revealed a larger response to object inspection compared to mental rotation. The coordinates indicate the location of the cluster centroid. Error bars represent 95% confidence intervals based on the pooled Mse from the corresponding ANOVA [31].

Fig. (5). The timecourse data from regions that revealed a larger response to mental rotation compared to object inspection. The coordinates indicate the location of the cluster centroid. Error bars represent 95% confidence intervals based on the pooled Mse from the corresponding ANOVA [31].

While these results mirror the activation cluster data, the timecourses provide additional information. As can be observed, not only are there amplitude differences between conditions, in some cases the shape of the hemodynamic response is also quite different across conditions and brain regions. In most of the timecourses, the onset of activation is 4-5 seconds after stimulus onset and the activation peaks between 12 and 14 seconds after stimulus onset. However, there are some regions that show a delayed onset of the hemodynamic response (e.g., the right prefrontal cortex – BA 10), and other regions that show two activation peaks, an additional earlier peak about 7 seconds after stimulus onset (e.g., medial superior extrastriate – BA 19). Finally, there were regions that revealed different shaped hemodynamic responses relative to the condition (e.g., right parietal cortex – superior BA 40). These differences in the timecourse across regions and conditions are discussed below.

There are a number of processing nodes within the visual cortex (e.g., early visual processing regions and regions within both the inferior and superior extrastriate) that appear to be involved in the current study. The involvement of early visual processing regions in the tasks used in the current experiment is expected due to the use of visual stimuli. No differential activation was predicted in these regions (BA17 and 18) and none was observed (see Fig. (3)). As shown, the timecourses for the object inspection and mental rotation conditions were very similar and lie almost exactly on top of each other.

In addition to early visual processing regions, several regions of the extrastriate cortex were found to be involved in the imagery network. Interestingly, three different time-course patterns were observed in extrastriate. In the regions that revealed a larger amplitude response for object inspection compared to mental rotation, the timecourse revealed two peaks (medial occipital regions including left and right lingual gyri and the medial superior extrastriate – see Fig. (4A-C). Both neuroimaging and lesion studies have implicated posterior ventral cortex, including inferior extrastriate (IES, which includes fusiform and lingual gyri), in object memory [12,13,32,33]. In fact, IES was found to be involved when subjects matched stimuli for semantic meaning as well as for structural properties suggesting that this occipital region is involved in a common memory network [32]. An explanation for the involvement of IES in object memory is that the region is involved in the processing of high-level perceptual descriptions of objects [13]. Again, in the current study the IES, specifically the bilateral lingual gyri, was found to be more involved during object imagery and it revealed the two-peak timecourse.

The early peak may be related to retrieving from memory information about the objects depicted in the question while the later peak may be related to evaluating the information retrieved and responding. Although both conditions elicited a response from the lingual gyri, the response was significantly greater for the object inspection compared to the mental rotation condition. This may reflect a more detailed, intensive search through memory for the object inspection condition. A similar pattern of activation was observed in this region in a previous study comparing haptic and visual imagery [34]. In that study greater reliance on the IES was observed during imagery of haptic object properties such as roughness and hardness compared to visual properties like shape and size. There the explanation for the difference in the involvement of IES was that making material judgments required the retrieval of more detailed object information from memory. A similar explanation can be given here in that the object inspection condition relies on the retrieval of more detailed object attributes than does mental rotation, which relies primarily only on shape information.

The more lateral regions of the occipital cortex, extending into the left middle temporal gyrus, unlike the medial occipital regions, showed a greater response to the mental rotation than the object inspection condition. The inferior occipito-temporal cortex revealed a hemodynamic time-course that peaked 14 seconds after stimulus onset (see Fig. (5A-C)). The region is similar to the location (similar Ta-lairach coordinates) found in previous object processing tasks focusing on shape, the lateral occipital complex [35-38]. One possible explanation for the current result is that although shape processing is a component of both object inspection and mental rotation, the mental rotation condition relies more on shape information. In addition, the manipulation component of the mental rotation task may be expected to place an additional demand on the shape orientation processing associated with the lateral occipital complex. There is some evidence to support this hypothesis. For example, in a recent mental rotation study using Cooper figures [39] of varying shape complexity, it was found that the activation in a similar region of the occipito-temporal cortex revealed not only main effects of shape complexity and amount of rotation, but also an interaction between the shape complexity and the amount of rotation [19]. These results indicate that shape processing is affected by mental rotation and suggests that the greater involvement of the region during the task in the current study may be due to the manipulation demands of the condition.

Several studies have shown that the region at the junction of the superior and inferior parietal cortex, the intraparietal sulcus (IPS), is involved in visuo-spatial processing, particularly when that image is manipulated. For example, the region has been routinely found to be activated during mental rotation tasks [4,5,19,24,27]. In the current study greater activation was observed in this region, bilaterally, for mental rotation compared to the object inspecition condition. The focus of that activation can be found in the superior portion of BA40, bilaterally. Interestingly, when examining the timecourses, these regions not only revealed a much larger amplitude response for mental rotation compared to object inspection, but the activation onset begins much earlier for mental rotation (see Fig. (5D,5E)). Again, this seems to indicate that the regions are involved in “determining the answer” (manipulation) for mental rotation, but only involved late (during evaluation and responding) for object inspection. While the parietal region has been found to be involved in mental rotation, it has also been found to be linked to image generation as well [6]. It may be that the early response for the spatial condition is associated with the generation and rotation of objects. For object inspection it may be that image generation occurs later, after the object properties have been extracted from memory. This hypothesis would account for the condition timecourse differences within the parietal cortex. However, further studies are necessary to disambiguate these two processes.

The prefrontal cortex, including bilateral BA 6 and right BA 10, was found to be more involved during mental rotation than object inspection. These regions have been long associated with spatial working memory processing [40–42]. For example in a study examining a group of stroke patients with lesions to the right middle frontal gyrus (which includes BA 10), it was found that these patients were impaired in their ability to keep spatial information on-line during the Corsi block-Tapping task [40]. In the current study onset of the hemodynamic timecourse in BA10 appears to occur late in the trial for both imagery conditions, during the evaluation and response portion of the trial (see Fig. (5I)). It may be that the region is involved in maintaining the visual images of the objects in memory.

In addition to BA 10, activation was also observed in BA 6 in and around the superior frontal sulcus, bilaterally. As mentioned above, these regions have been linked to spatial processing and have been observed during several visuo- spatial tasks. Portions of premotor cortex lies in BA6. As stated earlier, previous studies of the mental rotation task have found the involvement of motor processing regions [3,20,21]). In addition to mental rotation, another visuo-spatial task that has consistently recruited BA 6 is the Tower of London [TOL; 43,44]. In a TOL study in which goal hierarchy was manipulated while leaving the minimum number of moves constant, activation within bilateral BA 6 was observed [44]. This activation was thought to be associated with the spatial manipulation requirements of the task. Here, the involvement of BA 6 occurs early during the mental rotation trial, as indicated by the early onset of the hemodynamic timecourse (see Fig. (5G,5H)). In the case of the mental rotation task the early processing may be related to the imaged movement of the objects. This fits in well with its previously hypothesized role.

In addition to the involvement of the medial occipital regions, object inspection also elicited a greater response from prefrontal regions, particularly those that have been associated with semantic memory processing, the inferior frontal gyrus. Neuroimaging studies examining single word processing (e.g., verb generation tasks) have found that the inferior frontal gyrus, particularly BA47, is involved in semantic memory processing [14,15,45]. Petersen and colleagues [46], for example, examined a task in which subjects monitored a word list for instances of dangerous animals. Relative to a passive viewing baseline task, activation at or near BA 47 was found providing evidence for its role in semantic memory. In addition, during a verbal imagery task in which subjects listened to spatial words (e.g., “rotate”) and used them to assemble mental images, no inferior frontal gyral activation was detected [22]. This suggests that left BA47, as has been suggested previously [14], may be involved in controlled semantic retrieval processes; meaning the strategic retrieval and/or manipulation and evaluation of stored information. Furthermore, although both object inspection and mental rotation require the retrieval of information from memory, given that more detailed object attributes must be retrieved during object inspection, it may be expected that a greater degree of controlled retrieval processes is required for object imagery. The hemodynamic timecourse data also provides some evidence for this hypothesis. Left BA47 shows a much faster rise time for the object inspection compared to the mental rotation condition, suggesting that it is more involved early (when retrieving information) for object inspection and only later (when evaluating and responding) during mental rotation (see Fig. (4D)).

The right posterior lobe of the cerebellum, like the inferior frontal gyrus, revealed greater involvement for object inspection than mental rotation. The cerebellum has primarily been linked to motor processing. The timecourse observed in the cerebellum appears to support that associated function in that the activation onset is late for both conditions, when subjects would be making a motor response (see Fig. (4F)). However, several recent studies have suggested that the cerebellum is involved in a number of cognitive functions including object naming [47] and verbal working memory [48–50]. For example, in a study using transcranial magnetic stimulation (TMS) to disrupt the functioning of the right cerebellum in healthy adults, a decrease in the performance of a verbal working memory task was observed [50]. It has been suggested that the right cerebellum works together with the left inferior frontal gyrus during verbal working memory. However, further studies are required to determine the precise role of the cerebellum in imagery.