Response time (RT) is a frequently used behavioral measure to evaluate cognitive abilities. Little is known about the neural basis of the RT. We have tried to uncover the neural mechanism of the RT by measuring generalized fractional anisotropy (GFA) using diffusion spectrum imaging (DSI) ¹. We formed hypotheses as follows. [H1] Subjects with faster RT have greater GFA; [H2] subjects with faster RT by the right hand have greater GFA in the left hemisphere, and vice versa; [H3] subjects with faster RT by auditory stimulation have greater GFA in the auditory radiation, whereas by visual stimulation, the optic radiation.We developed a protocol of DSI on a GE 3T MRI (Discovery MR750) using the following parameters: 56 axial slices interleaved, TR 8000 ms, TE minimum, slice thickness 2.5 mm, FOV 20*20 cm², resolution 80 x 80, max b-value 4000 sec/mm² and 101 directions. We acquired DSI of 22 normal controls (F/M = 11/11, age range 20-26, Edinburgh handedness score -100 to 100) who also underwent an RT experiment (outside the scanner) with 4 conditions of 2 cue modalities (visual or auditory presentation of a word) by 2 response modalities (left or right hand button press). The DSI datasets of all subjects were used to construct a group template ^2-3, extract whole brain fiber tracts and compute individual GFAs along with these tracts ⁴. Greater GFA indicates greater neural connectivity. We specifically analyzed bilateral pairs of the corticospinal tract (CST) that ended up to the cortical hand area (Hand), the auditory radiation (Auditory) and the optic radiation (Optic) (6 fiber tracts in total; Fig. 1). Each tract (100 steps) was sectioned into quarters to use as GFA measures (Fig. 2). In addition to each measurement of RT (Vis_L, Vis_R, Aud_L, Aud_R), we will report results by the following measures: mean of all RT (meanRT), mean of RT with visual cues (meanVis), mean of RT with auditory cues over visual cues (AovV). We performed 2 types of statistical tests. [Stat1] ANCOVA with independent variables of RT (divided into halves by longer/shorter), dependent variables of GFA measures and a covariate of the individual mean GFA of the whole brain. [Stat2] T-test with independent variables of GFA measure (greater/smaller) with dependent variables of RT measures.The scanning and the template construction were successfully completed. We did not obtain significant results for H1 by Stat1 with all 6 fibers (within-factor 2 [LR] by 3 fibers by 4 sections). Thus, we conducted Stat1 by each pair of 3 fibers (within-factor 2 [LR] by 4 sections). We found that subjects with faster meanRT had a greater GFA in the CST Hand at the 4th quarter near the cortex (Fig. 3a). For H2, Stat2 indicated that subjects with greater GFA in the 2nd quarter of the left CST Hand responded faster in the Vis_R (Fig 3b), whereas subjects with greater GFA in the 1st quarter of the right CST Hand responded faster in the Vis_L (Fig. 3c). For H3, we found that the greater AovV, which indicated relative slowness of RT by auditory stimulation to that by visual stimulation, was associated with greater GFA in the 4th quarter of the left auditory radiation (Fig. 3de). Moreover, greater GFA in the same fiber portion yielded faster RT during Vis_L, Vis_R and mean Vis (Fig. 3f), whereas no significant differences were found during Aud_L and Aud_R.We found that faster RT was associated with higher fiber connectivity in the portion near the cortex of the CST (H1, Fig. 3a). Left and right specializations were indicated in the deep portions of the same fibers (H2, Fig. 3bc). Results for AovV (Fig. 3de) appeared contradictory to H3 because they indicated that faster RT by visual presentation was associated with greater GFA in the left auditory radiation. Additionally, greater GFA in the same fiber portion yielded faster RT during visual presentation (Fig. 3f). The results might indicate that the faster RT came from the faster language processing, because the significant results were found in the auditory radiation only in the left hemisphere near the cortex (4th quarter).By the power of DSI, we at the first time demonstrated that the speed of RT was associated with the neural fiber connectivity specifically the corticospinal tract that connected to the cortical hand area. Speed of language processing was also likely to influence RT.