Differential electrophysiological response during rest, self-referential, and non-self-referential tasks in human posteromedial cortex

Abstract

The electrophysiological basis for higher brain activity during rest and internally directed cognition within the human default mode network (DMN) remains largely unknown. Here we use intracranial recordings in the human posteromedial cortex (PMC), a core node within the DMN, during conditions of cued rest, autobiographical judgments, and arithmetic processing. We found a heterogeneous profile of PMC responses in functional, spatial, and temporal domains. Although the majority of PMC sites showed increased broad gamma band activity (30-180 Hz) during rest, some PMC sites, proximal to the retrosplenial cortex, responded selectively to autobiographical stimuli. However, no site responded to both conditions, even though they were located within the boundaries of the DMN identified with resting-state functional imaging and similarly deactivated during arithmetic processing. These findings, which provide electrophysiological evidence for heterogeneity within the core of the DMN, will have important implications for neuroimaging studies of the DMN.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

The PMC boundaries and fMRI/electrode location. (A) The PMC includes posterior cingulate [PC; i.e., Brodmann areas (BA) 23a and 23b], and retrosplenial cortex (RSC; BA29/30), along with medial parietal BA 31 and 7 m. The RSC extends anteriorly in the depth of the callosal sulcus adjacent and lateral to the PC area BA23a up to the midcingulate level, as shown in the sketch of the coronal section of the brain from the level of the midcingulate gyrus (green line). The boundaries of the PMC are easily defined by the corpus callosum (cc), the marginal branch (mb) of the cingulate sulcus (cgs), and the parieto-occipital medial sulcus (poms). These anatomical boundaries were used for classifying electrodes as PMC or non-PMC. (B) Medial view of the DMN derived from independent component analysis (color bar reflects significance of voxel correlation with selected component) of rsfMRI data and location of intracranial electrodes in each of the four subjects (s1–s4). PMC electrodes are shown as diamonds (non-PMC as circle); all excluded electrodes are indicated with black fill. The seizure onset zone was found to be located in the depth of parieto-occipital sulcus (subject 1), cuneus (subject 2), LPC (subject 3), and posterior temporal region (subject 4).

Fig. 2.

Differential electrophysiological response in the PMC and non-PMC during rest and math conditions. (A) ERSP maps during rest and math conditions for electrodes located within the right PMC and LPC in subject 2. (B) Across trials, GP increased in the PMC 384 ± 138 ms (median ± SE) after the onset of rest cue and persisted throughout the trial (5 s), whereas the LPC showed only a transient increase in GP of 318 ± 217 ms after the onset of rest cue. During the math condition, the PMC showed decreased GP, whereas the LPC displayed an increase in GP 257 ± 40 ms after the onset of math stimuli until it ended shortly before the subject responded. ERSPs during the math task are aligned to the time of stimulus onset (stim), the midpoint of onset-to-response-time (mid), and the time of response (response).

Fig. 3.

Temporal profile of broad gamma activity during transitions between nonrest and rest. (A) The temporal profile of relative GP (RGP) change in a representative PMC electrode for all subjects and averaged across two experiments. On the y axis the overall mean GP has a value of 1. The shading around each trace is the SE of RGP. The green trace belongs to the electrode shown in Fig. 2A, and the gray trace belongs to the only PMC electrode in subject 4. (B) Boxplot values for the RGP in five different epochs of transition between nonrest and rest for the 12 of 17 PMC electrodes with major increase of GP (see below). Each boxplot reflects the median (central notch mark), 25th, and 75th percentiles (upper and lower box edges), with whiskers extending to minimum and maximum values (medians are significantly different at P = 0.05 if notch widths do not overlap). These epochs, which are marked I–V in A, were as follows: (I) last 2 s of nonrest; (II) transition from nonrest to rest (200-ms black screen and 300-ms rest cue); (III) remaining rest period (4.7 s); (IV) 500 ms of transition from rest to nonrest (without ISI; Fig. S1); and (V) 1.5 s of nonrest. (C) The response onset latency values for the traces in subjects 1–3. Trials are sorted according to their response onset latency values in cumulative distribution. Each point on the curve represents the time of GP rise for one trial. The latency values for each of the three traces is significantly shorter than the corresponding random latency (black curves; P < 0.001; Wilcoxon rank test). (D) Distribution of latency values vs. mean RGP (in two experiments) for all PMC electrodes with increased gamma activity during rest. The counts of response onset latency values (Right) suggest that the majority of electrodes had shorter latency than the mean random latency (horizontal solid black line) ± SD (dashed lines).

Fig. 4.

The DAI distribution. (A–D) The distribution of DAI values for PMC and non-PMC electrodes during rest (A), math (B), autobiographical (C), and self (internal and external) (D) conditions for all experiments. The DAI of most PMC electrodes is positive during rest (A) and negative during math condition (B). The DAI values in PMC and non-PMC electrodes are not different during autobiographical or self-internal/external conditions and are distributed around zero. (E) The color of each electrode denotes DAI during rest in each of the four subjects. PMC electrodes are shown as diamonds (non-PMC as circle); all excluded electrodes are indicated with black fill.

Fig. 5.

Regional and functional specificity of gamma activity. (A) There was a significant interaction between task condition and electrode location. Mean DAI of PMC compared with non-PMC electrodes is significantly higher during rest, significantly lower during math, and not significantly different during the autobiographical condition (*P < 0.003, Bonferroni corrected). Although A shows the results of group analysis, the same profile holds for the PMC in each subject. (B) Two PMC electrodes (one each from subjects 2 and 4) had significantly higher activity during the autobiographical condition compared with rest and math (*P < 0.02, Bonferroni corrected). Both electrodes were located in the ventral posterior cingulate gyrus in ventral BA23a (subject 2; Fig. S4) and BA29/30 (subject 4; Fig. 6). (C) The histogram of DAI values is shown for all electrodes during the rest condition (two experiments). We assigned red or blue colors to the DAI values 1 SD greater or less than the mean, respectively, with the remainder set to green. (D) Location of all electrodes in all subjects on a spatially normalized glass brain in Talairach space colored with respect to the rest DAI values as defined in C (PMC, diamonds; non-PMC, x). (E and F) For all electrodes and in all experiments, the RGP was plotted during rest vs. math (E) or rest vs. autobiographical condition (F). Color convention in E and F is the same as in C and D. The value of 1 on horizontal and vertical axes in E and F denotes the overall mean GP during that condition. Note that in E, PMC electrodes (diamonds) fall in the right lower quadrant; i.e., they are active during rest (right of vertical axis of 1) and deactivated during math (below the horizontal axis of 1). The solid black line with the yellow band shows the regression line with its SE. Four gray markers in F denote electrodes in B (two sites and two experiments).

Fig. 6.

Broad gamma activity in the PMC during autobiographical condition. (A–C) ERSP plots for a PMC electrode (A) during autobiographical (B) and math (C) conditions (subject 4). The location of the PMC electrode (diamond) is proximal to the retrosplenial cortex as outlined in Fig 1. ERSPs are aligned as per Fig. 1. (D) Mean DAI for this electrode across all presented conditions. The mean DAI was significantly different across conditions [F(2,237) = 51.97 P < 0.001] with the autobiographical condition being significantly higher than rest and math conditions, which were also significantly different (*P < 0.02, Bonferroni corrected).