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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Hum Brain Mapp. Author manuscript; available in PMC 2013 September 1.
Published in final edited form as:
PMCID: PMC3235253
NIHMSID: NIHMS290479

Role of Medial Cortical Networks for Anticipatory Processing in Obsessive-Compulsive Disorder

Abstract

Recurrent anticipation of ominous events is central to obsessions, the core symptom of obsessive–compulsive disorder (OCD), yet the neural basis of intrinsic anticipatory processing in OCD is unknown. We studied non-medicated adults with OCD and case matched healthy controls in a visual-spatial working memory task with distractor. Magnetoencephalography was used to examine the medial cortex activity during anticipation of to-be-inhibited distractors and to-be-facilitated retrieval stimuli. In OCD anticipatory activation to distractors was abnormally reduced within the posterior cingulate and fusiform gyrus compared to prominent activation in controls. Conversely, OCD subjects displayed significantly increased activation to retrieval stimuli within the anterior cingulate and supplementary motor cortex. This previously unreported discordant pattern of medial anticipatory activation in OCD was accompanied by normal performance accuracy. While increased anterior cortex activation in OCD is commonly viewed as failure of inhibition, the current pattern of data implicates the operation of an anterior compensatory mechanism amending the posterior medial self-regulatory networks disrupted in OCD.

Keywords: OCD, MEG, anticipatory top-down control, posterior medial self-regulatory networks, compensatory mechanism

INTRODUCTION

Anticipation provides a primary basis for mental regulation. In the visual domain it involves top-down processing engaging the frontal-parietal-extrastriate network. It serves as a memory-driven attentional biasing for behaviorally relevant stimuli (Posner and Raichle, 1994; Desimone and Duncan, 1995). Persistent anticipation of unwanted, disturbing events is an epitome of obsessions, the core symptom of obsessive-compulsive disorder (OCD). Thus, understanding the neural mechanism of the anticipatory system sited in the medial brain is essential for understanding the pathophysiology of the disease. OCD is well defined by measures of obsessions, compulsions and lingering cognitive, emotional and social deficits, but the mechanism of anticipatory networks has not been studied. Here, we investigate the properties of intrinsic anticipatory dynamics in the medial cortex of non-medicated subjects with OCD and case-matched healthy controls to actively inhibited distractors and to facilitated retrieval stimuli.

High neuronal organization has been found within intrinsic brain activity (Shulman et al., 1997; Raichle et al., 2001). A consistent network of regions has displayed deactivation in target-oriented tasks and increased activation during intrinsic monitoring of ones own psychological state (Raichle & Mintun, 2006). Commonly, this network involves the medial prefrontal area, posterior cingulate and parahippocampal regions (Shulman et al., 1997; Raichle & Snyder, 2007). However, task-induced deactivation represents only one of many varieties of the brain’s intrinsic functionality (Salinas and Sejnowski, 2001; Buckner et al., 2008). Another is the capacity to relate past experience to anticipating and preparing for future events (Ingvar, 1985). Anticipatory top-down attentional activity is the focus of the current study.

In healthy humans the pattern of cortical activation linked to anticipation of future events, involves multiple areas of medial brain including the rostral and dorsal anterior cingulate cortex (Shulman et al., 1997; Petit et al., 1998), the superior frontal and pre-supplementary motor region (Picard and Strick, 1996), and the posterior cingulate/retrosplenial cortex (Maddock, 1999). Connectivity studies of intrinsic attentional states (Fox et al., 2005) emphasized the highly interconnected posterior-medial complex, with posterior cingulate/retrosplenial cortex (PCG/Rsp), and inferior parietal area (Kobayashi and Amaral, 2003; Buckner et al., 2009). Since recurrent anticipation of events is prime in OCD, a model of top-down intrinsic anticipatory processing provides a conceptual framework well suited to study the underlying neural mechanism.

There are no neuroimaging reports on intrinsic anticipatory processing and medial brain in OCD (Broyd et al., 2009), but neuroimaging studies using evoked-response paradigms repeatedly emphasize the importance of abnormally increased activation in the prefrontal ventral and anterior cingulate regions as one component of abnormally functioning cortico-thalamo-striatal circuitry (Rauch et al., 2001; Dougherty et al., 2002). Here, we use MEG and a visual-spatial working memory task, delayed matching-to-sample with distractor (DMSTD) to investigate the role of medial cortex in top-down anticipatory processing in OCD. In DMSTD the encoded sample-stimulus to be retained and responded to must compete for limited top-down attentional resources, engaging both the dorsal fronto-parietal and the ventral fronto-temporal pathways. While the former has been associated with early visual-spatial attentional processing (Corbetta & Shulman, 2002), the latter has been shown to enhance firing rates in the pre-retrieval anticipatory stage (Gregoriou et al., 2009). Because of the high similarity between the sample, distractor and retrieval stimuli the matching-to-sample tasks require an effortful competitive inhibitory selection processes (Posner & Raichle, 1994). Further, the anticipation of the retrieval targets in working memory tasks has been described as an active, top-down-monitored facilitation (Corbetta & Shulman, 2002). Thus, using the above framework and the unique high temporal resolution of MEG (>1ms) we examined cortical activation at four stages of DMSTD: (1) anticipation of to-be-inhibited distractor (AD); (2) post-distractor processing (PD); (3) anticipation of to-be-facilitated retrieval stimuli (AR); and (4) post-retrieval processing (PR).

Anticipatory processing engages attentional inhibitory resources for task-specific networks (Mishkin et al., 1983; Worden et al., 2000), leading to “biased competition” between stimulus-related groups of neurons (Desimone, 1998). In agreement, event-related fMRI studies found a stronger neuronal activation by to-be-inhibited distractors than by target stimuli (Fize et al. 2000). A prolonged inhibition is found in cells neighboring the areas activated by target stimuli (Duncan et al., 1997). Single unit studies (Desimone & Duncan, 1995), modeling theories (Salinas & Sejnowski, 2001) and neuroimaging observations (Pessoa et al., 2009; Fox et al., 2006) concur, that processing of the anticipated target is facilitated in that a specific set of neurons is primed for processing of a particular stimulus before it is presented. Thus priming signals feed back from higher order brain regions to primary visual regions, to sensitize neurons within the related network, and to enhance and accelerate their responses.

If the top-down effortful competitive inhibition in delayed sample-matching tasks is the source of increased activity during anticipation of both distractors and retrieval stimuli, then will the pattern of medial brain spatio-temporal dynamics reflect a generic widespread increased anticipatory activation in OCD, or will the pattern of activation be differentiated by the contextual identity of DMSTD stages. If the latter is true, we expect that during anticipation of a distractor, activity in the rostral cingulate might be reduced given its link to the amygdala for emotional control and to the striatum for cognitive inhibitory control (Botvinick et al., 2001; Chamberlein et al., 2008). Meanwhile, anticipation of competitive, effortful processing of distractor stimuli will produce increased activation in the posterior cingulate cortex, the major neural node of intrinsic, self-regulatory network (Raichle & Snyder, 2007) and dorsal cingulate/premotor cortex associated with top-down prediction of sample retrieval (Pickard & Strick, 1996). An increased activation is expected to retrieval stimuli in the dorsal anterior cingulate cortex, given its prominent connectivity to the seed areas of cognitive and memory control, the dorsal prefrontal cortex and hippocampal formation (Corbetta and Schulman, 2002; Devinsky et al., 1995).

MATERIALS AND METHODS

Participants

Eight non-medicated OCD outpatients and healthy controls (C) were case-matched for gender (4 males per group) age (OCD: 28.6yrs; C: 28.0yrs), handedness (all right-handed), years of education (OCD: 13.75; C: 13.00), as well as normal scores on verbal neuropsychological measures. Other psychiatric disorders (The Structured Clinical Interview; DSM–IV), recreational drug use and clinical depression symptoms during the preceding three months were exclusionary. The level of symptoms in OCD was moderate-to-severe (Y-BOCS; Goodman et al. , 1989; obsessions: 14.0, compulsions: 11.2). The clinical history of the control group was unremarkable. The study was approved by the Institutional Review Board at the School of Medicine, UNM and Massachusetts General Hospital.

Visual–Spatial Delayed Matching-to-Sample Task with Distractor (DMSTD)

The DMSTD (Figure 1) contained black and white checkerboard patterns. Each sample stimulus (a square containing 9 checks) extended to 1º 40’ vertically x 1º 40’ horizontally. The small stimulus was chosen to keep the total size of the retinal image close to the size of macula lutea, thus within the high and constant level of visual acuity. The task involved: (i) presentation of an encoding sample-stimulus for 200 ms, (ii) presentation of a distractor for 200 ms; (iii) 1000 ms post-encoding, and (iv) presentation of retrieval stimuli: two similar checkerboards for 200 ms. Retrieval stimuli were presented 3200 ms post-encoding. The subjects were instructed to match the sample to retrieval stimuli by pressing a corresponding button with the left or right index finger. Speed and accuracy were emphasized. 164 trials were divided into two runs. Each run included 82 stimuli. To reduce the probability of the automatic preparatory contingent negative variation response (CNV), that could obscure our frontal MEG measures, 15% of these randomly distributed trials were jittering time trials. These trials were not included in our task-related data analysis. The jittering trials varied the time between stimuli (inter stimulus intervals, ISI), whereas the presentation time for sample and retrieval stimuli was constant across the study. With variable ISIs in jittering trials the total time of a single run was about 8 min.

Figure 1
The visual-spatial delayed matching-to-sample task with distractor (DMSTD). The number above each panel indicates the duration of the stimulus presentation in milliseconds.

Magnetoencephalography (MEG) data acquisition

MEG signals were recorded using a Vectorview™ system (Elekta Neuromag, Finland) in four pairs of OCD and case matched controls, and a Neuromag-122 system in the remaining four pairs. The measurements were carried out in a magnetically shielded room (Imedco AG, Switzerland). The two systems were calibrated with identical phantoms. Previous evidence suggests that different types of MEG systems provide consistent source estimates (Weisend et al. 2007; Ou et al., 2007). For comparability between data from both systems, only planar gradiometers were used in the analysis (204 in Vectorview, 122 in Neuromag-122). The location of the head with respect to the sensors was determined using head-position indicator coils attached to the scalp (Uutela et al., 2001). The data were sampled at 300 (Neuromag-122) or 600 samples/s (Vectorview), with an anti-aliasing low-pass filter set at 100 Hz and 200 Hz, respectively. The stimuli were presented with a Liquid Crystal Display projector onto a back-projection screen placed 1.7 m in front of the subject. Blinks and eye movements were monitored with vertical and horizontal EOG.

Structural magnetic resonance imaging (MRI)

A set of 3-D T1-weighted magnetic resonance images (MRI) using a 1.5T Picker or Siemens systems were acquired several days after the MEG session. The MRI and MEG coordinate systems were aligned by matching scalp surface points digitized prior to the MEG acquisition to the scalp surface reconstructed from the MRIs.

MEG-evoked activation within task–relevant ROIs and time windows

Regions of Interest

The anatomically predetermined regions of interest, ROIs (Figure 2) were transformed to an average cortical surface using a morphing procedure based on sulcal and gyral patterns in FreeSurfer (Dale et al., 1999; Fischl et al., 1999). The same procedure was applied to the MEG source estimates for group analysis within the task-relevant time windows and ROIs. For statistical comparisons we employed the actual current strength values given by the depth-weighted MNE in each ROI.

Figure 2
The right medial surface of the brain showing marked regions of interest (ROIs): G indicates gyrus, S, sulcus. Individually reconstructed cortical surfaces were averaged across subjects, and inflated for better visualization of sulcal regions. From anterior ...

Time windows

Our major study aim was to capture anticipatory activity before the onset of distractor, limiting any confound of this measure by still ongoing processing of the encoded sample. The flow of activation along visual pathways in humans, was shown to set a window of 100–400 ms needed for visual information processing to reach the parietal-frontal and motor brain regions (Corbetta and Shulman, 2002; Foxe and Simpson, 2002). To reduce the influence of encoding processing on the measurements of pre-distractor anticipatory activity we increased the skip window to 610 ms from the onset of the sample stimulus before we began measurements. Thus, a time window of 590 ms (610 –1200 ms) before the onset of distractor (at 1200 ms), constitutes “the anticipation of distractor” (AD). A sibling 590 ms long time window was used for measurements of “the anticipation of retrieval” (AR, 2610 – 3200 ms). This window of time was reported by the subjects to be a time of effortful rehearsal of the sample stimulus and preparation for a prompt response. Measures of MEG activity were also obtained during post-distractor active inhibition (PD, 1410 – 2400 ms) and post-retrieval stimulus processing (Post-Retrieval, PR, 3410–3800 ms). The length of the latter window was determined by the shortest RT in our tested samples, to prevent a response-motor confound on cognitive brain measures.

MEG source estimation

Spatial distributions of cortical currents underlying the MEG signals were estimated using the minimum-norm approach (Hamalainen and Ilmoniemi, 1984; Dale et al., 2000). The current locations (3000 points per hemisphere, 7-mm spacing) were restricted to the gray-white matter interface segmented from the MRI using the FreeSurfer software (Dale et al., 1999; Fischl et al., 1999). No orientation constraint was used. The single-layer boundary-element model (BEM) was used in the forward solution. The cortically-constratined source estimates were computed using MNE software http://www.nmr.mgh.harvard.edu/martinos/userInfo/data/sofMNE.php.

The continuous raw data were re-averaged off line with a band-pass of 0.1- 40 Hz. Epochs contaminated by eye movement or blink artifacts were rejected (peak-to-peak EOG threshold 150 μV). The noise-covariance matrix was estimated from the 500-ms baseline period preceding each encoding stimulus. Depth-weighted minimum-norm estimates (MNE) as well as dynamic Statistical Parametric Maps (dSPM) were computed at 10 ms intervals (Dale et al. , 2000). The regularization parameter in the computation of the minimum-norm solutions was set to correspond to amplitude signal-to-noise ratio 3 in the whitened data. The dSPM was obtained by normalizing the MNE solutions by the square root of estimated current variance at each location, obtained by mapping the noise-covariance matrix, to the source space. We used the dSPM for displaying the spatial distribution of the significance of the activation in a particular task-relevant area. For statistical comparisons we employed the actual current strength values given by the depth-weighted MNE.

RESULTS

Behavior

The performance accuracy was high in both groups and not significantly different [C: 94.1%, SD=7.0, OCD: 96.4% SD=2.4%, t(6)=0.20 p=0.8]. RTs were significantly longer in OCD (OCD: 684ms; C: 591ms; t(6)= 4.10, p=0.006).

MEG

Measures of MEG activation in regions of interest (ROIs) and time windows (TW)

Figure 2 illustrates regions of interest (ROIs) on the medial wall of the brain estimated using anatomical sources (Nolte, 2008). Considering a relatively low 6–8mm MEG resolution six broader ROIs were analysed containing neighbouring gyrus and sulcus: (1) dorsal anterior cingulate cortex dACC (encompassing activity in dACG and dACS); (2) rostral anterior cingulate cortex rACC (rACG and rACS); (3) posterior cingulate cortex, PCC (PCS and PCG/Rsp); (4) fusiform gyrus, FG (FG and collateral sulcus, COS); (5) superior frontal gyrus, SFG, and (6) sensory visual regions, SV, (calcarine sulcus, CS and cuneus, Cun).

Figure 3 displays group differences in brain activity for task-relevant time windows. In both distractor related time windows, AD (610–1200 ms) and PD (1410- 2400 ms), the OCD group has lower activity in the right posterior medial cortex. However, the OCD group has more activity in both the rostral and dorsal regions of the anterior cingulate when anticipating retrieval, (AR, 2610–3200 ms). OCD group also displays higher activation during post-retrieval processing, (PR, 3410–3800 ms).

Figure 3
Group differences (t-values) for different latency windows. Red and yellow indicate higher activation in OCD subjects than in C subjects, whereas light blue and dark blue indicate higher activation in C subjects. During the anticipation of distractor ...

Figure 4 shows estimated MNE measures in the sensory visual areas of the medial brain, cuneus and calcarine sulcus. Four time windows were selected (details in Methods) to obtain MEG measurements for statistical analysis: “anticipation of a distractor” (AD, 610 –1200 ms), “anticipation of retrieval” (AR, 2610 – 3200 ms), “post-distractor active inhibition” (PD, 1410 – 2400 ms) and “post-retrieval active processing” (PR, 3410–3800 ms).

Figure 4
Estimated cortical activation across the DMSTD epoch. The Minimum-Norm Estimate (MNE) waveforms were averaged across subjects within each group (blue line: C, red line: OCD). The time windows (task stages) of interest are marked in color shades: Red: ...

Figure 5 shows Minimum Norm Estimate (MNE) activity across groups of subjects in the anterior and posterior medial cortex within relevant cognitive time windows of the DMSTD.

Figure 5
A. Estimated activity (MNE) in three anterior ROIs: rACG, rACS and dACS. Increased activation is evident in subjects with OCD compared to HC throughout the whole task epoch. The activity during retrieval stage (PR) was higher in OCD than in C in each ...

ANOVA was conducted on stages of DMSTD relevant to anticipation of competitive inhibition. Since prior studies linked inhibitory processing with the right-hemisphere (Garavan et al. , 1999), and since visual-spatial difficulties reported in OCD are commonly related to the right hemisphere (Purcell et al., 1998), we decided to fit the ANOVA model to the MEG MNE measures in the right and left hemisphere separately, with pair-matched subjects as a random effect, and fixed effects of Group (OCD, C), Time Window (4 levels, AD, PD, AR, PR), and ROIs (6 levels: dACC, rACC, PCC, FG, SFG, SV).

ANOVA for the left hemisphere showed no significant main effect of the Group [F(1,7)=1.644; p=0.241], but significant effect for the Time Window [F(3, 322) =41.708, p=0.0001], and the ROIs factor [F(5, 322)=37.350, p=0.0001]. Although the interactions Group x ROI reached the statistical significance [F(5,322)=1.451, p=0.021], the interactions Group x Time Window (p=0.697), Time Window x ROI factor (p=0.093), and Group x ROI x Time Window (p=0.827) were not statistically significant. Thus, post hoc analysis of particular ROIs or particular time windows was not warranted. However, a question was raised about one of the highly predictable a priori findings reported in OCD, the abnormally increased activity in the dorsal anterior cingulate region (Rosenberg and Hanna, 2000). During the AR time window, the two-sided paired t-tests revealed statistically significantly higher activation in the dorsal anterior cingulate for OCD [OCD=2.44, C= 1.89; t (7)=2.620, p=0.034].

The ANOVA for the right hemisphere showed significant effects for the Time Window [F(3, 322) 56.144, p<0.0001], ROI [F(5, 322) 51.548, p<0.0001], but no significant effect for Group [F(1,7)0.80, p=0.80]. Significant interactions included: Group x Time Window [F(3,322)=3.666, p=0.013]; Group x ROI factor [F(5,322)2.648, p=0.023], Time Window x ROI [F(15,322)2.597, p=0.001], and Group x Time Window x ROI [F(15,322)2.124, p=0.009]. Considering the significant interactions, the published findings and current neurobiological models of OCD (Rosenberg and Hanna, 2000; Dougherty et al., 2007), we tested several group-contrasts using two-sided paired t-tests. In the AD time window the OCD group displayed lower activation in the right posterior cingulate region [OCD=3.210, C=3.480; t(7)=2.47, p=0.043], fusiform gyrus region (OCD=3.010, C=3.376; t(7) =3.537, p=0.001], and in the right visual-sensory region, but the latter did not quite reach statistical significance [OCD=1.36, C=1.68; t(7)=1.178, p=0.201]. In the AR time window statistically significantly higher activation in OCD subjects was shown for the right dorsal anterior cingulate area [OCD =2.301, C=1.667; t(7)=3.55, p=0.009]. In the PR time window the OCD displayed significantly larger activation in all regions including visual-sensory areas [SV: OCD=5.12, C=4.17; t (7)= 3.54, p= 0.003].

DISCUSSION

Medial brain dissociation between anticipatory activation for inhibition and facilitation

Contrary to our expectations, the posterior medial areas to anticipation of distractors were less active in OCD subjects than in controls, suggesting a failure in engaging inhibitory self-regulatory networks. In contrast, the anterior cingulate regions extending to supplementary motor areas displayed significantly increased activation in OCD, mostly during top-down anticipatory facilitation of retrieval. Based on area-specific group-differences, we propose the operation of a mechanism compensating for abnormal posterior self-regulatory networks through increased engagement of the anterior medial regions. Consistent with such proposal is the high performance accuracy in OCD accompanied by the prolonged response time. Thus, we think much of the increase in MEG activation in OCD is not due to a direct failure of inhibition but may result from extra-compensatory processing.

The reduced anticipatory activation in the posterior-medial and fusiform regions plays a role in efficacy of self-regulatory networks in OCD

The abnormally low anticipatory activation in the right posterior cingulate and fusiform regions in OCD (AD window), suggests dysfunctions in the posterior network related to anticipation of inhibition. To a lesser degree the reduced activation was also found in post-distractor (PD) time window. Yet, the performance accuracy of OCD subjects matched controls. Prior studies have shown that anticipation of a distractor guides specific “cognitive readiness” to be employed in the top-down inhibitory control for upcoming events. The higher posterior medial MEG activation during the AD window in controls (see Fig. 3B) is consistent with reported by other laboratories an active competitive-inhibition of task-irrelevant networks (Jensen et al., 2002). Consequently, the reduced activation in the medial posterior regions during anticipation and processing of distractor stimuli may suggest a limitation in self-regulatory inhibitory resources. Concurring, persistent failure in inhibiting trivial visual details plays a central role in cognitive phenomenology of OCD.

The posterior cingulate cortex is an important neural center coordinating efforts of attentional self-control. It has a strong anatomical and functional relationship with the lateral inferior parietal regions linked to top-down inhibition of distractors (Friedman-Hill et al., 2003). The present results, while unexpected, are consistent with accumulating evidence about structural and functional abnormalities within the posterior brain in patients with OCD (Nordahl et al., 1989; Ciesielski et al., 2005; Menzies et al., 2008). Since the posterior-medial cortex is richly connected with the medial prefrontal and parahippocampal regions, as well as with lateral prefrontal and parietal areas (Suzuki and Amaral, 1994), its abnormally low intrinsic activity observed here may alter multiple anticipatory and stimulus-response systems. The present study reveals a possible role of one of them in OCD, the area of fusiform gyrus. FG has been considered a major component of the intrinsic mode processing, attentional modulation and maintenance of memory (Lepsien and Nobre, 2006). While associated with context-based processing of visual memory retrieval, the FG participates in top-down modulation of recognition patterns (Kourtzi and Kanwisher, 2001). FG may play, therefore, an important role in the preparatory stage for predictive memory-based self-control, and as such it may be a part of an important neural circuit whose malfunction contributes to the phenomenology of OCD.

Increased anticipatory activation in the anterior cingulate and pre-supplementary motor regions may indicate an effortful compensatory mechanism

How do OCD subjects match normal performance accuracy on the difficult visual-spatial DMSTD, when the key node of the instrumental network, the posterior cingulate cortex exhibits abnormally low activation? A possible answer comes from the pattern of activation in the anterior medial brain. While our prediction about the leading role of the prefrontal medial cortex in reflecting increased activation in OCD to anticipation of distractor was not supported by the current data, the anterior medial areas did display increased activation across several time-windows including AD, particularly around retrieval (AR and PR epochs). Such globally increased activation may reflect a task-nonspecific attentional vigilance and increased motivation. This view is consistent with association of rostral anterior cingulate/orbital cortex with emotion and motivation (Gusnard et al., 2001). The commonly accepted model of pathophysiology in OCD relies on functional and structural abnormalities in the prefrontal-striatal-thalamic circuit. The ventral prefrontal cortex with rich connections to ventral caudate has been found to exhibit an increased activation in almost all OCD studies (but see Chamberlain et al., 2008). Our present findings are in line with those earlier studies.

One possible view of the increased anticipatory activation in the anterior cingulate and supplementary motor areas is that it may reflect an effortful identification of sample stimulus and motor response. This interpretation is consistent with single unit studies on top-down prediction of retrieval of a sample in a spatial delayed-response task, which revealed the presence of anticipatory cells in the anterior cingulate sulcus and caudal premotor area (Picard & Strick, 1996). Within proposed conflict-solving networks the prefrontal dorsal-medial regions have been found in OCD subjects to respond to tasks with high conflict detection and monitoring (Kerns et al., 2004; Ciesielski et al., 2010). Our data concurs with these earlier findings, but also suggests a novel perspective on the working memory mechanism in OCD. Since the anticipation of retrieval involves multifaceted inhibitory control of conflicts between the encoded sample, distractor, and incoming retrieval stimuli, the enhanced anterior medial activity may be a signature of a compensatory mechanism. Such a mechanism maintains extensive motivational, monitoring and inhibitory control, providing on-line amendment to dysfunctional posterior self-regulatory networks. In line with this OCD subjects were as accurate as normal controls on the task, whereas their reaction times were delayed by almost a tenth of a second. Thus, OCD subjects appear to be taking noticeably more time and more effort than controls to ensure accurate performance.

In conclusion, the abnormally reduced anticipatory activation to distractors in the posterior medial cortex implicates a disrupted top-down self-regulatory control system in subjects with OCD. And yet, they performed as accurately or better than controls. This profile of behavioral and MEG data implicates the operation of a compensatory processing mechanism in OCD aiming high performance accuracy. The increased anterior medial cortex activation, commonly seen as a marker of inhibitory deficits in OCD, may demonstrate here, at least in part, an adaptive brain plasticity.

Acknowledgments

This study was supported in part by the National Center for Research Resources, National Institute of Health (P41RR14075) and MGH/MIT/HMS Martinos Center for Biomedical Imaging. We thank Drs. David Cohen, Julia Stephen and Robert Elmasian for support to this project. The authors declare no conflict of interest.

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