Subjects Performances and Functional MRI
Twenty healthy normally sighted subjects were tested. Correct retrieval judgments were made on 73.6% of trials for the studied words (“Hits”) and 64.5% for new words (“Correct rejections”). In the comparison between Hits and Correct rejections, the following brain areas were activated: left IPS, right PCu, left superior temporal gyrus (STG), right middle temporal gyrus (MTG), left middle frontal gyrus, right inferior frontal gyrus, and cerebellum ().
Hit versus correct rejection
Group Study in DTI Tractography
We used DTI tractography to reconstruct fibers originating from IPS and PCu. The distribution of fiber terminals from 20 subjects is shown in A
. Probabilistic maps were obtained by a statistical nonparametric bootstrap method (Lazar and Alexander 2005
; Takahashi et al. 2007
), and displayed in B
(note that only terminal points of the reconstructed fibers are displayed in A
, whereas the entire fibers are displayed in B
). The IPS had connections with lateral temporal cortex (STG [BA 22], the MTG [BA 21], and the fusiform gyrus [FG, BA 37]) and bilateral superior colliculi (A
, upper row). PCu had connections with MTL (hippocampus, parahippocampal gyrus, the occipital cortex [BA 17, 18, 19], and posterior cingulate cortex (A
, lower row).
Functional connectivity analysis was performed from the same ROIs with DTI fiber-tracking analyses. Regions with a significant functional correlation with an activated region in PCu (Talairach coordinates: x, y, z = 24, −62, 22) is shown in C (upper row) and D (yellow and green). Activity in bilateral hippocampi, parahippocampal gyri, occipital cortices (BA 17, 18, 19), posterior insula, anterior cingulate cortices (BA 32, 24), posterior cingulate cortices (BA 23, 31), PCu (BA 7), inferior parietal lobes (BA 39) was highly correlated with activity in PCu (P < 0.05, corrected for whole-brain multiple comparisons at voxel level). C (lower row) and D (blue and green) show maps of significant functional correlation with an activated region in left IPS (x, y, z = −44, −66, 46). The activity in bilateral frontal operculum (BA 47), IPS (BA 7), inferior parietal lobes (BA 39, 40), superior parietal lobes (BA 7), supplementary motor area (BA 8), PCu (BA 7), middle frontal gyri (BA 8), left MTG (BA 21, 37), inferior frontal gyrus (BA 44), superior frontal gyrus (BA 6) was highly correlated with activity in the left IPS (P < 0.05, corrected for multiple comparisons at voxel level).
Segregations of the Two Pathways in Anatomical and Functional Connectivity
The terminal points of reconstructed fibers from IPS and PCu exhibited very little overlap (11.0% compared with the total terminal points from IPS, or 3.3% compared with those from PCu; using a threshold of 5 subjects). Functional connectivity (at the threshold of P < 0.05, corrected for multiple comparisons for a whole brain at voxel level) also exhibited little overlap (5.68% compared with all the correlated areas of IPS, and 3.58% compared with those of PCu). At a lower threshold of z > 0.3 (mean across all the subjects), overlapping areas were 10.1% compared with functionally correlated areas with IPS, and 6.92% compared with those with PCu (D, yellow: areas correlated with PCu, blue: areas correlated with IPS). Overlaps were found in posterior cingulate/PCu and bilateral inferior parietal lobes (D, brown).
Functional Segregations of the Two Pathways
Mean percent signal changes in PCu (A) and IPS (B) showed clearly different patterns in the “Hit” condition. In PCu, there is almost no signal change in the “Hit” compared with the control condition, whereas IPS showed almost the same amount of signal change with “Hit” and “Miss” conditions. In both areas, “False alarm” and “Correct rejection” conditions showed decreased signal changes compared with baseline.
Figure 2. (A, B) Mean percent signal changes in the activated cluster in PCu and IPS. (A) Mean percent signal changes of the cluster in PCu (including the peak voxel, x, y, z = 24, −62, 22). (B) Mean percent signal changes of the cluster in IPS (including (more ...)
Next, we show that the pattern of activity in the clusters in the left MTG and parahippocampal gyrus depend on the memory performance of the subjects (Hits, Misses, False alarms, and Correct rejections). These clusters were defined by functional connectivity analysis with the IPS and the PCu, respectively. For the MTG (C
= 4.66, P
= 0.0018, and there were significant differences between Misses and False alarms, and Misses and Correct rejections (Tukey's t
< 0.05). For the parahippocampal gyrus (D
= 3.6, P
= 0.009, and there were significant differences between Misses and False alarms, and Misses and Correct rejections (Tukey's t
< 0.05). Correlations between the z
-scores for functional connectivity and success rates (Buchel et al. 1999
; Hampson et al. 2006
) were also examined across all the subjects (n
= 20). The functional connectivity between IPS and MTG was positively correlated to success rates (r
= 0.63, P
= 0.0028) and that between PCu and MTL was negatively correlated to success rates (r
= −0.7167, P
= 0.004, see also Supplementary Fig. S1
). Thus, the MTG and parahippocampal gyrus show a similar pattern of activity to the IPS and PCu, which suggests that the connections between the IPS and MTG and that between PCu and parahippocampal gyrus are involved in successful memory retrieval.