**2.2.2 Experimental stimuli**

The visual stimulus consisted of a target ("X") with a diameter of 1º eccentricity that was shown for 50 ms, 7º to the right or left of the central point on a screen located 130 cm in front of the subjects. The auditory stimulus was the sound of a 1,000 Hz sine wave presented to either ear for 50 ms. Visual and auditory experiments included space tasks (S), time tasks (T), and control tasks (N). The tasks were designed in a factorial format and are shown in Table 1.


Table 1. Experimental tasks

Fig. 3. Central cues used in the experimental task. The spatial cue was used in the spatial attention tasks. For the stimulus, the right or left half of the cube was lit to give the subjects information on the target location (right or left). The temporal cue was used in the temporal attention tasks. When the target came within a short cue–target interval, the inside circle was lit; and when it came after a long cue–target interval, the outside circle was lit. The neutral cue was used in the control task and gave neither spatial nor temporal information. A double 'V' in the centre of the cue indicated a visual experiment, whereas a double 'A' indicated an auditory target.

Cue stimuli (shown in fig. 3) were used to direct the subjects' attention to a particular target location or onset time. The neutral cue provided neither spatial nor temporal information; the spatial (space) cue directed the subjects' attention to the left or right; and the temporal (time) cue directed their attention to a short or long stimulus onset time. The flow chart of one trial is shown in Fig. 4. The time from the end of stimulus presentation to the onset of the next stimulus was defined as the interval of the stimuli (IOS) and was either 2,200 or 3,700 ms. We recorded the RT, the time from the presentation of a stimulus to a response indicated by a reaction key. The subjects responded to a right stimulus using the middle finger of their right hand and to a left stimulus with the forefinger of their right hand. The subjects performed 60 trials under each condition.

#### **2.2.3 fMRI scanning**

40 Neuroimaging for Clinicians – Combining Research and Practice

The subjects were 16 healthy, right-handed students aged 21–32 years. Informed consent was obtained from each participant following a detailed explanation of the study. During fMRI scanning, visual and auditory stimuli were generated on a personal computer and presented to the subjects via a projector-screen–mirror system and headphones,

The visual stimulus consisted of a target ("X") with a diameter of 1º eccentricity that was shown for 50 ms, 7º to the right or left of the central point on a screen located 130 cm in front of the subjects. The auditory stimulus was the sound of a 1,000 Hz sine wave presented to either ear for 50 ms. Visual and auditory experiments included space tasks (S), time tasks (T), and control tasks (N). The tasks were designed in a factorial format and are shown in

Fig. 3. Central cues used in the experimental task. The spatial cue was used in the spatial attention tasks. For the stimulus, the right or left half of the cube was lit to give the subjects information on the target location (right or left). The temporal cue was used in the temporal attention tasks. When the target came within a short cue–target interval, the inside circle was lit; and when it came after a long cue–target interval, the outside circle was lit. The neutral cue was used in the control task and gave neither spatial nor temporal information. A double 'V' in the centre of the cue indicated a visual experiment, whereas a double 'A'

**2.2 Method 2.2.1 Subjects** 

respectively.

Table 1.

**2.2.2 Experimental stimuli** 

Table 1. Experimental tasks

indicated an auditory target.

Modality

Task Visual Auditory

spatial VS AS temporal VT AT neutral VN AN We used a Philips 1.5 Tesla Magnetom Vision whole-body MRI system to measure the brain activation using a head coil. The imaging area consisted of 32 functional gradient-echo planar imaging (EPI) axial slices (voxel size 3×3×4 mm3, TR=3,000 ms, TE=50 ms, FA=90°, 64×64 matrix) that were used to obtain T2\*-weighted fMRI images in the axial plane. The EPI imaged the entire cortex. For each task, we obtained 124 functional volumes. Before the EPI scan, a T2-weighted volume was acquired for anatomical alignment (TR=3,500 ms, TE=100 ms, FA=90°, 256×256 matrix, voxel size=0.75×0.75×4 mm3). The T2 image acquisition used the same slices as the functional image acquisition.

#### **2.2.4 Data analysis**

Reaction times were used as the behavioural data. The RT data during the fMRI experiment were analysed using repeated measures analysis of variance (ANOVA; SPSS 12.0j for Windows). For each task, 60 RTs were acquired from each subject. We used the average of the RT data for the ANOVA, except for error trials (all subjects reacted with an accuracy above 90%). Therefore, we had 16 RT data for each task. Six tasks were presented in this experiment, and we compared the visual and auditory tasks separately. Between the modalities (visual and auditory), we compared VS and AS, VT and AT, and VN and AN.

 For the functional images, we used MRIcro to change the DICOM files into MRIimg and MRIhdr files. In each task, the functional images of the first four volumes were not used for the data analysis. The DICOM files from the 5th through 124th scan were exported as MRIima and MRIhdr files. In addition, the DICOM files for the T2 images were exported as MRIimg and MRIhdr files.

The functional images were analysed using statistical parametric mapping (SPM5, Wellcome Department of Cognitive Neurology, London, UK). The functional images from each task were realigned using the first scan as a reference. The T2-weighted anatomical images were co-registered to the first scan in the functional images. Then, the co-registered T2-weighted anatomical images were normalised to standard T2 template images as defined by the Montreal Neurological Institute. Finally, these spatially normalised functional images were smoothed using an isotopic Gaussian kernel of 8 mm.

Statistical analyses identified the brain areas shared by visual (VS, VT) and auditory (AS, AT) attention and the brain areas that were selectively engaged by each task. To eliminate the brain activation caused by finger motion, we told the subjects to click the reaction key ten times during every rest. As a control task, we used VN for the visual attention task and AN for the auditory attention task.

Early Detection of Alzheimer's Disease with Cognitive Neuroscience Methods 43

The areas of significant activation are shown in Fig. 5, and the right frontal cortex had more activations than the left. In the parietal cortex, BA7/40 was activated bilaterally, and the

In this comparison, significant activation occurred only in the bilateral parietal cortex. In a previous study (Coull & Nobre, 1998), the medial premotor (BA6) cortex had significant

activation bilaterally when the visual temporal task was compared to baseline.

More activation occurred in the left premotor (BA6) and left parietal (BA40) cortices.

Fig. 5. Activations in visual attention and auditory attention (p=0.001, voxel=0). Left sides

We used SPSS for the paired t-test. The comparison of RTs across visual tasks showed a significant difference between VN and VS (t(15)=2.53, p<0.05) and between VN and VT (t(15)=2.82, p<0.05). AS and AT (t(15)=4.86, p<0.001) and AN and AS (t(15)=6.19, p<0.001)

A previous study (Coull & Nobre, 1998) used the resting state as the baseline to be consistent with previous reports using visual fixation controls (Corbetta et al., 1993). In addition, the neutral condition engages attention and orients attention between two spatial

In this study, we focused on the activation without finger movement by asking the subjects to click the reaction key ten times during rest. We compared the activation in each task with the resting state. With the exception of the visual and auditory cortices, no significant activation occurred in the N task. Therefore, we used the N task as the baseline to examine

**VS–VN** 

**VT–VN** 

**AS–AN** 

**AT–AN** 

visual cortex had more activations on the left.

Right STG was observed in this comparison.

are right hemispheres in a-b, respectively.

locations and two temporal intervals.

**2.4 Discussion** 

differed significantly, whereas AN and AT did not.

**2.4.1 Baseline: At rest or during the neutral task** 

Fig. 4. Flow of a trial. The visual spatial cue indicated spatial information but provided no information about the cue–target interval. The cue was lit for 100 ms, and after the cue– target interval (300 or 1,800 ms), the target was illuminated for 50 ms.


Table 2. Reaction time during each task (±SD)

#### **2.3 Results**

#### **2.3.1 Behavioural data**

Behavioural data were derived from the performance during the fMRI experiment. The reaction time for each task (Table 2) was computed from the data for the 16 subjects (the average of 16×55=880 trials).

#### **2.3.2 fMRI data**

From the imaging results comparing the visual tasks with the other tasks, all of the visual tasks activated the bilateral visual association cortex (BA18/19, Brodmann area). In VN, significant activation occurred only in the visual association cortex (BA18/19). From the imaging results comparing the auditory tasks with the other tasks, all of the auditory tasks activated the bilateral visual association cortex (BA18/19) because in the auditory tasks, the cues were visual as they were in the visual tasks. In addition, all of the auditory tasks activated the bilateral primary and auditory association cortex (BA41/42). In AN, significant activation occurred only in BA18/19/41/42. Therefore, as a baseline, we used VN for the visual tasks and AN for the auditory tasks.

This study focused on visual spatial attention, visual temporal attention, auditory spatial attention, and auditory temporal attention. Fig. 3 compares the activation in VS–VN, VT– VN, AS–AN, and AT–AN.
