Aberrant error processing in relation to symptom severity in obsessive–compulsive disorder: A multimodal neuroimaging study

Background: Obsessive–compulsive disorder (OCD) is characterized by maladaptive repetitive behaviors that persist despite feedback. Using multimodal neuroimaging, we tested the hypothesis that this behavioral rigidity reflects impaired use of behavioral outcomes (here, errors) to adaptively adjust responses. We measured both neural responses to errors and adjustments in the subsequent trial to determine whether abnormalities correlate with symptom severity. Since error processing depends on communication between the anterior and the posterior cingulate cortex, we also examined the integrity of the cingulum bundle with diffusion tensor imaging. Methods: Participants performed the same antisaccade task during functional MRI and electroencephalography sessions. We measured error-related activation of the anterior cingulate cortex (ACC) and the error-related negativity (ERN). We also examined post-error adjustments, indexed by changes in activation of the default network in trials surrounding errors. Results: OCD patients showed intact error-related ACC activation and ERN, but abnormal adjustments in the post- vs. pre-error trial. Relative to controls, who responded to errors by deactivating the default network, OCD patients showed increased default network activation including in the rostral ACC (rACC). Greater rACC activation in the post-error trial correlated with more severe compulsions. Patients also showed increased fractional anisotropy (FA) in the white matter underlying rACC. Conclusions: Impaired use of behavioral outcomes to adaptively adjust neural responses may contribute to symptoms in OCD. The rACC locus of abnormal adjustment and relations with symptoms suggests difficulty suppressing emotional responses to aversive, unexpected events (e.g., errors). Increased structural connectivity of this paralimbic default network region may contribute to this impairment

Network Dynamics Underlying Speed-Accuracy Trade-Offs in Response to Errors

The ability to dynamically and rapidly adjust task performance based on its outcome is fundamental to adaptive, flexible behavior. Over trials of a task, responses speed up until an error is committed and after the error responses slow down. These dynamic adjustments serve to optimize performance and are well-described by the speed-accuracy trade-off (SATO) function. We hypothesized that SATOs based on outcomes reflect reciprocal changes in the allocation of attention between the internal milieu and the task-at-hand, as indexed by reciprocal changes in activity between the default and dorsal attention brain networks. We tested this hypothesis using functional MRI to examine the pattern of network activation over a series of trials surrounding and including an error. We further hypothesized that these reciprocal changes in network activity are coordinated by the posterior cingulate cortex (PCC) and would rely on the structural integrity of its white matter connections. Using diffusion tensor imaging, we examined whether fractional anisotropy of the posterior cingulum bundle correlated with the magnitude of reciprocal changes in network activation around errors. As expected, reaction time (RT) in trials surrounding errors was consistent with predictions from the SATO function. Activation in the default network was: (i) inversely correlated with RT, (ii) greater on trials before than after an error and (iii) maximal at the error. In contrast, activation in the right intraparietal sulcus of the dorsal attention network was (i) positively correlated with RT and showed the opposite pattern: (ii) less activation before than after an error and (iii) the least activation on the error. Greater integrity of the posterior cingulum bundle was associated with greater reciprocity in network activation around errors. These findings suggest that dynamic changes in attention to the internal versus external milieu in response to errors underlie SATOs in RT and are mediated by the PCC

Failure to mobilize cognitive control for challenging tasks correlates with symptom severity in schizophrenia

Deficits in the adaptive, flexible control of behavior contribute to the clinical manifestations of schizophrenia. We used functional MRI and an antisaccade paradigm to examine the neural correlates of cognitive control deficits and their relations to symptom severity. Thirty-three chronic medicated outpatients with schizophrenia and 31 healthy controls performed an antisaccade paradigm. We examined differences in recruitment of the cognitive control network and task performance for Hard (high control) versus Easy (low control) antisaccade trials within and between groups. We focused on the key regions involved in ‘top-down’ control of ocular motor structures – dorsal anterior cingulate cortex, dorsolateral and ventrolateral prefrontal cortex. In patients, we examined whether difficulty implementing cognitive control correlated with symptom severity. Patients made more errors overall, and had shorter saccadic latencies than controls on correct Hard vs. Easy trials. Unlike controls, patients failed to increase activation in the cognitive control network for Hard vs. Easy trials. Reduced activation for Hard vs. Easy trials predicted higher error rates in both groups and increased symptom severity in schizophrenia. These findings suggest that patients with schizophrenia are impaired in mobilizing cognitive control when presented with challenges and that this contributes to deficits suppressing prepotent but contextually inappropriate responses, to behavior that is stimulus-bound and error-prone rather than flexibly guided by context, and to symptom expression. Therapies aimed at increasing cognitive control may improve both cognitive flexibility and reduce the impact of symptoms

Dissociable Genetic Contributions to Error Processing: A Multimodal Neuroimaging Study

Background: Neuroimaging studies reliably identify two markers of error commission: the error-related negativity (ERN), an event-related potential, and functional MRI activation of the dorsal anterior cingulate cortex (dACC). While theorized to reflect the same neural process, recent evidence suggests that the ERN arises from the posterior cingulate cortex not the dACC. Here, we tested the hypothesis that these two error markers also have different genetic mediation. Methods: We measured both error markers in a sample of 92 comprised of healthy individuals and those with diagnoses of schizophrenia, obsessive-compulsive disorder or autism spectrum disorder. Participants performed the same task during functional MRI and simultaneously acquired magnetoencephalography and electroencephalography. We examined the mediation of the error markers by two single nucleotide polymorphisms: dopamine D4 receptor (DRD4) C-521T (rs1800955), which has been associated with the ERN and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), which has been associated with error-related dACC activation. We then compared the effects of each polymorphism on the two error markers modeled as a bivariate response. Results: We replicated our previous report of a posterior cingulate source of the ERN in healthy participants in the schizophrenia and obsessive-compulsive disorder groups. The effect of genotype on error markers did not differ significantly by diagnostic group. DRD4 C-521T allele load had a significant linear effect on ERN amplitude, but not on dACC activation, and this difference was significant. MTHFR C677T allele load had a significant linear effect on dACC activation but not ERN amplitude, but the difference in effects on the two error markers was not significant. Conclusions: DRD4 C-521T, but not MTHFR C677T, had a significant differential effect on two canonical error markers. Together with the anatomical dissociation between the ERN and error-related dACC activation, these findings suggest that these error markers have different neural and genetic mediation

Abnormally persistent fMRI activation during antisaccades in schizophrenia: a neural correlate of perseveration

Objective: Impaired antisaccade performance is a consistent cognitive finding in schizophrenia. Antisaccades require both response inhibition and volitional motor programming, functions that are essential to flexible responding. We investigated whether abnormal timing of hemodynamic responses (HDRs) to antisaccades might contribute to perseveration of ocular motor responses in schizophrenia. We focused on the frontal eye field (FEF), which has been implicated in the persistent effects of antisaccades on subsequent responses in healthy individuals. Method: Eighteen chronic, medicated schizophrenia outpatients and 15 healthy controls performed antisaccades and prosaccades during functional MRI. Finite impulse response models provided unbiased estimates of event-related HDRs. We compared groups on the peak amplitude, time-to-peak, and full-width half-max of the HDRs. Results: In patients, HDRs in bilateral FEF were delayed and prolonged but ultimately of similar amplitude to that of controls. These abnormalities were present for antisaccades, but not prosaccades, and were not seen in a control region. More prolonged HDRs predicted slower responses in trials that followed an antisaccade. This suggests that persistent FEF activity following an antisaccade contributes to inter-trial effects on latency. Conclusions: Delayed and prolonged HDRs for antisaccades in schizophrenia suggest that the functions necessary for successful antisaccade performance take longer to implement and are more persistent. If abnormally persistent neural responses on cognitively demanding tasks are a more general feature of schizophrenia, they may contribute to response perseveration, a classic behavioral abnormality. These findings also underscore the importance of evaluating the temporal dynamics of neural activity to understand cognitive dysfunction in schizophrenia

EEG Correlates of Attentional Load during Multiple Object Tracking

While human subjects tracked a subset of ten identical, randomly-moving objects, event-related potentials (ERPs) were evoked at parieto-occipital sites by task-irrelevant flashes that were superimposed on either tracked (Target) or non-tracked (Distractor) objects. With ERPs as markers of attention, we investigated how allocation of attention varied with tracking load, that is, with the number of objects that were tracked. Flashes on Target discs elicited stronger ERPs than did flashes on Distractor discs; ERP amplitude (0–250 ms) decreased monotonically as load increased from two to three to four (of ten) discs. Amplitude decreased more rapidly for Target discs than Distractor discs. As a result, with increasing tracking loads, the difference between ERPs to Targets and Distractors diminished. This change in ERP amplitudes with load accords well with behavioral performance, suggesting that successful tracking depends upon the relationship between the neural signals associated with attended and non-attended objects

Interactions between working memory and visual perception: An ERP/EEG study

How do working memory and perception interact with each other? Recent theories of working memory suggest that they are closely linked, and in fact share certain brain mechanisms. We used a sequential motion imitation task in combination with EEG and ERP techniques for a direct, online examination of memory load's influence on the processing of visual stimuli. Using a paradigm in which subjects tried to reproduce random motion sequences from memory, we found a systematic decrease in ERP amplitude with each additional motion segment that was viewed and memorized for later imitation. Highfrequency (N20 Hz) oscillatory activity exhibited a similar positiondependent decrease. When trials were sorted according to the accuracy of subsequent imitation, the amplitude of the ERPs during stimulus presentation correlated with behavioral performance: the larger the amplitude, the more accurate the subsequent imitation. These findings imply that visual processing of sequential stimuli is not uniform. Rather, earlier information elicits stronger neural activity. We discuss possible explanations for this observation, among them competition for attention between memory and perception and encoding of serial order by means of differential activation strengths. © 2007 Elsevier Inc. All rights reserved

Geometric structure and chunking in reproduction of motion sequences

Learning by imitation is fundamental to human behavior, but not all observed actions are equally easy to imitate. To understand why some actions are more difficult to imitate than others, we examined how higher-order relationships among the components of a stimulus model influenced the fidelity with which an action could be observed and then reproduced. With static contours, perception and short term memory are strongly influenced by contour geometry, particularly by the presence and distribution of curvature extrema. To determine whether analogous relationships among subcomponents of a seen action would be important in encoding the action for subsequent reproduction, we manipulated actions’ spatio-temporal geometry. In three experiments we measured imitation fidelity for sequences of randomly-directed, linked motions of a disc. The geometry of the disc’s motion path strongly affected the accuracy of subsequent imitation: When the disc moved along a trajectory whose components were fairly consistent in their directions, imitation was strikingly better than when with irregular, jagged trajectories. A second experiment showed that this effect depended not upon co-variation in stimulus models ’ spatial extent, but rather on the relationship between successive movement directions. In a final, learning experiment, subjects had multiple opportunities to view and reproduce each model. The effect of the model’s geometry persisted throughout the learning process, suggesting that it does not depend upon variables such as familiarity or expectancy, but is somehow inherent to the pattern generated by the disc’s motion. Our findings suggest that when analyzing seen actions, the brain privileges regular, consistent curvatures, grouping components that form a coherent shape into a unified “chunk”. Inconsistencies among the directional components of a motion sequence cause the sequence to be chunked into additional components, which increases the load on working memory, undermining the fidelity with which the sequence can be imitated

Working Memory and Visual Perception Compete for Attention: An ERP/EEG Study

How do working memory, perception and attention interact with each other? Recent theories of working memory suggest that they are closely linked, and in fact share certain brain mechanisms. Here we use a sequential motion imitation task for a direct, online examination of memory load’s influence on the processing of visual stimuli. Based on event-related potentials (ERPs) and frequency analysis of the electroencephalogram (EEG), we show that the processing of successive incoming visual stimuli becomes less and less effective as additional items have to be held in working memory. Using a task in which subjects tried to reproduce random motion sequences from memory, we found a systematic decrease in ERP amplitude with each additional motion segment that was viewed and memorized for later imitation. High-frequency (>20 Hz) oscillatory activity exhibited a similar position-dependent decrease. When trials were sorted according to the accuracy of subsequent imitation, the amplitude of the ERPs correlated with behavioral performance: The larger the amplitude, the more accurate the imitation. As both ERP amplitude and high-frequency oscillations are known to reflect attention-driven visual processing, our results suggest that visual working memory is tightly linked to attention and interferes with visual perception in a load-dependent manner. Such a tradeoff between memory and perception may underlie fundamental properties of working memory, such as limited capacity and primacy effects