Chapter 025, Cingulate Cortex

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The stimuli were English words, all one- or two-syllable nouns, between 4—6 letters in length. Each trial consisted of the following series of events: memory set presentation 2. Probe responses were button presses indicating whether the probe word was an item in the immediately presented memory set positive probe ; right index finger or was not a member of this set negative probe ; right middle finger.

Positive and negative probes were randomly intermixed with equal frequency in all blocks i. Probe recency i. However, across blocks, recency was differentially associated with interference by varying the frequency of recent negative vs. Interference expectancy conditions LE, HE were performed in a blocked fashion in separate scanning runs. Ten scan runs were acquired, with five blocks of one interference expectancy condition, followed by five blocks of the other interference expectancy condition, with the order of interference expectancy conditions counterbalanced across subjects.

Each run lasted Each block of trials consisted of 10 trials intermixed with 20 null fixations, for a total of trials per expectancy condition. Stimuli were projected to participants with an LCD projector onto a screen positioned at the head end of the bore. Participants viewed the screen through a mirror attached to the head coil.

A fiber-optic, light-sensitive key press interfaced with the PsyScope Button Box was used to record participants' behavioral performance. Whole-brain images were collected on a Siemens 1. High-resolution 1. Each of the 10 scanning runs provided whole-brain volumes consisting of 16 contiguous, 8-mm thick axial slices, acquired parallel to the anterior-posterior commissure plane 3. Functional images were movement and artifact corrected, intensity normalized within each scanning run, and temporally aligned within each brain volume. Prior to statistical analyses, functional images were re-sampled into 3 mm isotropic voxels, transformed into atlas space, and smoothed with a 9 mm FWHM Gaussian filter.

During task blocks, the inter-trial interval varied from 1 TR to 4 TRs, in an optimized logarithmic distribution, in order to create the necessary temporal jitter to allow deconvolution of event-related fMRI responses. Four null volumes were included in each scanning run to allow the scanner to ensure equilibrium of longitudinal magnetization, and were discarded prior to analysis. A general linear model approach [24] was used to estimate parameter values for event-related responses. Event-related effects were analyzed by computing parameter estimates for each time point within the hemodynamic response epoch i.

This approach to GLM estimation as opposed to a fit to predefined hemodynamic response function model has been found to be critical in estimating complex trials or multi-event-related responses in rapid event-related designs. Separate regressors were included for various nuisance effects e.

The mean GLM estimates during the 4 th and 5 th time points 7. Selecting time points subsequent to the peak in V1 increased the likelihood that positive deflections in activation reflect processes that occurred after the memory set i. These processes may include, but are not limited to, the active maintenance of goal representations and task-relevant information.

However, activity from these time points may also contain residual or extended processing from the memory set period, such as increased encoding or depth of processing of the memory set items. Probe-related activity corresponds to the two TRs that occur during the peak in primary motor cortex 7 th and 8 th time point.

Therefore, interference-control processes that affect activation at these time points likely occur concurrent with response selection and commission. Importantly, differences between recent and novel probes at these time points are unlikely to reflect activation prior to the onset of the probe, because the identity of the probe as recent or novel is unknown until its presentation.

Analyses were restricted to twenty-five ROIs within the canonical network engaged by WM and executive control tasks, as defined by previous meta-analyses See the second table in [25] and the fourth table and part B of the fifth figure in [26]. The resulting mask image, generated from spherical ROIs 10 mm radius centered on these published anatomical coordinates Table 1 , contained voxels, or 95, mm 3 in volume.

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This ROI mask was used to constrain analysis to only those voxels that were theoretically expected to be strongly associated with interference control during WM. We then identified voxel clusters from within these masks that showed particular interference control effects of interest.

These effects were tested through multiple contrasts, and a voxel cluster was only identified if it simultaneously satisfied each of the contrasts. For reactive control ROIs, we identified voxels that showed significantly greater activity for recent negative than novel negative probes, and also activity for recent negative probes was significantly greater than fixation baseline.

For proactive control ROIs, we identified voxels in which delay activity during HE trials was greater than fixation baseline, and also that delay activity was greater for HE trials than LE trials.

Andrew J. Todd and Fan Wang

To correct for multiple comparisons, we conducted Monte Carlo simulations as implemented in AlphaSim [28]. Previous studies utilizing the recent probes paradigm have shown behavioral interference effects decreased accuracy and slower RTs for recent negatives relative to novel negatives.

Furthermore, some studies have also shown facilitation greater accuracy and faster RTs for recent positives relative to novel positives. We examined both interference and facilitation effects due to recency, as well as whether these effects were modulated by gF and interference expectancy. There were no significant effects of, or interactions with, interference expectancy.

2-Minute Neuroscience: Limbic System

However, no other main effects or interactions were significant, suggesting that the magnitude of this interference effect was not modulated by gF or interference expectancy. Because some previous studies have found recency effects for positive probes i. However, this effect resulted from slower RT for recent positive probes relative to novel positive probes, rather than facilitation. Although effects of interference expectancy on behavioral performance were not statistically significant in the current sample, it should be noted that evidence was present in a prior pilot sample suggesting that the expectancy manipulation can affect interference control performance.

Data from a pilot sample of 41 participants suggested that interference expectancy affected the degree to which recency information influenced responding. RT interference for negative probes tended to be greater in the LE condition than in the HE condition ms vs. Therefore, although we believe that expectancy condition can affect interference control, the behavioral effects are relatively small and likely interact with gF.

Consequently, it is possible that the effect of expectancy was not statistically significant in the imaging sample simply due to a lack of power related to this small effect size. In summary, the behavioral results replicate the critical finding of interference for recent negative probes relative to novel negative probes. Furthermore, the results also suggest that high gF individuals had fewer errors overall than low gF individuals, and more specifically, a reduced tendency to make errors on recent negative trials.

This pattern supports the hypothesis that high gF individuals can exhibit better interference control than low gF individuals. The first step was to identify those brain regions that demonstrated interference-related probe activity, as defined by increased activity on recent negative probes, both relative to fixation and to novel negative probes. Because we hypothesized that interference expectancy might affect the neural mechanisms used to control interference during the task, we conducted separate analyses for the HE and LE conditions.

Indeed, the left IFG ROI replicates well the anatomical location associated with recent negative interference in many prior studies. For each subject, interference-related probe activity i. The percent signal change for the recency contrast i.

Publications Derived From HBTRC Tissue Samples (2000-2013)

This estimate of interference-related probe activity was extracted for each subject separately for the HE and LE conditions. Previous studies have demonstrated that recency had similar effects on activation of positive probes as is typically observed for negative probes. Therefore, we searched for regions that showed significantly increased activity for recent positive probes, both relative to novel positive probes and fixation.

Again, these analyses were conducted separately for the HE and LE conditions, to allow the possibility that interference expectancy might influence the neural mechanisms used to control effects of recency during the task. For each subject, the recency effect for positive probes i. A search for regions demonstrating significantly increased activity during the HE condition for recent positive probes, relative to both novel positive probes and fixation, yielded no significant ROIs.

An additional analysis was conducted to identify brain regions that demonstrated interference-related activity during the delay, rather than probe period. As discussed previously, we hypothesized that greater interference expectancy might engage neural mechanisms of proactive control that act to prevent interference before its onset. Therefore, interference-related effects during the delay were defined by increased delay-period activity in the HE condition, relative to both the fixation baseline and delay-period activity in the LE condition.

Because the presence of interference on any particular trial is unknown prior to the probe period, delay activity is not expected to vary with the recency and target status of the probe [15]. Therefore, in these analyses, delay-period activity was averaged across all trial types. This analysis identified eleven interference-related delay regions. We estimated interference-related delay activity by averaging the percent signal change for the delay contrast i.

However, the gF effect and gF x expectancy interaction were not significant. The above analysis procedure was conducted to detect regions that showed greater activity during the HE condition than the LE condition. To investigate the specificity of these effects, we conducted a parallel analysis to identify any possible regions that showed more delay activity for the LE than HE condition.

This suggests that the pattern of interference-related activity during the delay period was not simply an artifact of the analysis method, but rather a specific effect of interference expectancy on components of the core brain network associated with WM and interference control. The results of recent studies [14] and unpublished data from our laboratory suggest that some PFC regions might be capable of flexibly switching between proactive and reactive control modes. In the current study, several anatomical regions showed effects consistent with both proactive control during the HE condition and reactive control during the LE condition.

Therefore, we conducted a formal overlap analysis to investigate the degree to which specific regions exhibited a switch from one control mode to another depending upon interference expectancy Figure 1. This analysis failed to show regions in left IFG that showed both probe-related and delay-related interference effects. Timecourses extracted from the delay-related ROIs did not show significant probe-related effects, and timecourses extracted from the probe-related ROIs did not show significant differences between delay activity during HE and LE conditions Figure 2.

Voxels are color-coded according to the interference-related effects demonstrated by that region. LE: low interference expectancy; HE: high interference expectancy. Left lateral PFC regions did not show significant interference-related effects during both the delay and probe periods. These four panels show percent signal change for negative trials as a function of time.

The top two panels are timecourses from ROIs that showed interference-related effects during the delay period. The bottom two panels are timecourses from ROIs that showed interference-related effects during the probe period. Time points 4 and 5 reflect delay-period activity. Time points 7 and 8 reflect probe-period activity.

A Focus on the Functions of Area 25

However, outside of left IFG, the overlap analysis identified two probe-related interference ROIs that overlapped substantially with delay-related interference effects. However, as a portion of the total volume of the combined adjacent regions mm 3 , only 6. Therefore, the pattern of activation in this portion of lateral PFC may be best characterized by its delay-related effects. Second, a region in right medial frontal gyrus pre-SMA showed both probe-related and delay-related interference effects.

Within this pre-SMA region, the more anterior portion showed a delay-related interference effect, the more posterior portion showed a probe-related interference effect, and the central portion showed both effects. Of the total volume of the combined interference-related region mm 3 , Consequently, this suggests that pre-SMA may be best characterized as showing both forms of interference control. The ANOVAs reported above failed to show relationships of gF with interference-related probe activity or interference-related delay activity.