Extending the knowledge on performance monitoring in obsessive-compulsive disorder: Insights gained by electrophysiological recordings and deep brain stimulation.

Obsessive-compulsive disorder (OCD) is characterized by alterations in frontostriatal circuits and associated impairments in performance monitoring. The overactivity of the performance monitoring system is reflected by enhanced electrophysiological correlates during decision conflict (conflict-theta) and error processing (error-theta and error-related negativity, ERN). Besides the mediofrontal cortex, composing the source of these correlates, further brain structures are fundamentally involved in these cognitive processes. Particularly, the anterior limb of internal capsule (ALIC) and nucleus accumbens (NAc) are not only involved in performance monitoring but show partially also altered activity in OCD. Despite the importance of ALIC/NAc in performance monitoring observation of its electrophysiological activity during decision conflict and error processing are limited. Notably, ALIC/NAc has been established as target region for deep brain stimulation (DBS) for treatment resistant OCD and has proved to be clinically effective. Although, it is still unknown whether stimulation of the ALIC/NAc affects the aforementioned cortical correlates. In the first part of the present dissertation, electrophysiological activity during decision conflict and error processing from the cortex and the ALIC/NAc (by means of local-filed potentials, LFP) was investigated in patients with OCD (LFP-study). As expected, previous findings were successfully replicated cortical correlates of decision conflict (conflict-theta) and error processing (error-theta and ERN) were observed. Additionally, it was hypothesized that LFPs from the ALIC/NAc also comprises correlates of decision conflict (LFP-conflict-theta) and error processing (LFP-error-theta and LFP-ERN). Indeed, all three performance monitoring modulations were observed in the ALIC/NAc. Accordingly, ALIC/NAc seems to be involved in processes associated with monitoring of decision conflict and performance errors. Presumably, it provides the signal for the need of increased cognitive control to resolve the conflict and of behavioral adaptation to improve performance, respectively. Although, it was expected to find increased frontostriatal connectivity during decision conflict and error monitoring, this was not confirmed. Putatively, this could be explained by increased connectivity between both structures irrespective of cognitive control demands in OCD. Finally, possible interrelations between striatal correlates and symptom severity or symptom improvement by DBS in OCD were explored. Our results indicated an association of patients who exhibited smaller error signals (LFP-error-theta and LFP-ERN) with lesser symptom severity and with greater DBS efficacy. This links ALIC/NAc performance monitoring modulations to OCD symptomatology, possibly reflecting hyperactive performance monitoring, and connect this to attenuated response to DBS. In the second part of the present dissertation, the modulatory effect of DBS on cortical correlates of decision conflict (conflict-theta) and error processing (ERN) was investigated by comparing the correlates from pre-DBS state with stimulation on and stimulation off (Stimulation-study). It was hypothesized that acute DBS reduces conflict-theta and the ERN and that these effects would rebound after cessation of stimulation. In line with our hypotheses, the correlates were decreased by acute stimulation, indicating DBS-induced reduction of the pathologically overactive performance monitoring system. Contrary to our hypotheses, the rebound effect after cessation of stimulation was not observed for conflict-theta but at trend level for the ERN. Likely, DBS has only acute and no long-term effects on the performance monitoring system, which might become clearer by extending the stimulation off phase. Finally, possible interrelations between clinical efficacy of DBS with pre-DBS conflict-theta and the ERN and their changes through stimulation were explored. Our results associated patients who exhibited smaller pre-DBS ERN with greater DBS efficacy. In conclusion, this dissertation provides new insights on electrophysiological correlates of performance monitoring in OCD derived from ALIC/NAc and on the modulation of their cortical pendants by DBS. Further investigations, particularly involving long-term acquisition of LFPs, are required to further characterize ALIC/NAc activity during performance monitoring and its association with the pathophysiology of DBS. Also, additional studies are needed to confirm the interrelation between electrophysiological correlates and clinical parameters with regard to clinical applications in the future. Particularly, it should be further explored whether increased cortical and striatal error signals point toward a hyperactive performance monitoring system and are also related to attenuated clinical efficacy

Evoked Potentials during Language Processing as Neurophysiological Phenomena

The evoked, event-related potential of the EEG has been extensively employed to study language processing. But what is the ERP? An extensive discussion of contemporary theories about the neurophysiology underlying late ERPs is given. Then, in a series of experiments, domain-general perspectives on ERP components are tested regarding their applicability for language-related brain activity. A range of analysis methods (some of which have not been previously applied to the study of auditory sentence processing) such as single-trial analyses and independent component decomposition, demonstrate the degree to which domain general mechanisms explain the language-related EEG

An Introduction to EEG Source Analysis with an illustration of a study on Error-Related Potentials

International audienceOver the last twenty years blind source separation (BSS) has become a fundamental signal processing tool in the study of human electroencephalography (EEG), other biological data, as well as in many other signal processing domains such as speech, images, geophysics and wireless communication (Comon and Jutten, 2010). Without relying on head modeling BSS aims at estimating both the waveform and the scalp spatial pattern of the intracranial dipolar current responsible of the observed EEG, increasing the sensitivity and specificity of the signal received from the electrodes on the scalp. This chapter begins with a short review of brain volume conduction theory, demonstrating that BSS modeling is grounded on current physiological knowledge. We then illustrate a general BSS scheme requiring the estimation of second-order statistics (SOS) only. A simple and efficient implementation based on the approximate joint diagonalization of covariance matrices (AJDC) is described. The method operates in the same way in the time or frequency domain (or both at the same time) and is capable of modeling explicitly physiological and experimental source of variations with remarkable flexibility. Finally, we provide a specific example illustrating the analysis of a new experimental study on error-related potentials

Increased Error‐Related Brain Activity In Youth With Obsessive‐Compulsive Disorder And Unaffected Siblings

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96293/1/da22035.pd

Electroencephalographic Brain Dynamics Following Manually Responded Visual Targets

Scalp-recorded electroencephalographic (EEG) signals produced by partial synchronization of cortical field activity mix locally synchronous electrical activities of many cortical areas. Analysis of event-related EEG signals typically assumes that poststimulus potentials emerge out of a flat baseline. Signals associated with a particular type of cognitive event are then assessed by averaging data from each scalp channel across trials, producing averaged event-related potentials (ERPs). ERP averaging, however, filters out much of the information about cortical dynamics available in the unaveraged data trials. Here, we studied the dynamics of cortical electrical activity while subjects detected and manually responded to visual targets, viewing signals retained in ERP averages not as responses of an otherwise silent system but as resulting from event-related alterations in ongoing EEG processes. We applied infomax independent component analysis to parse the dynamics of the unaveraged 31-channel EEG signals into maximally independent processes, then clustered the resulting processes across subjects by similarities in their scalp maps and activity power spectra, identifying nine classes of EEG processes with distinct spatial distributions and event-related dynamics. Coupled two-cycle postmotor theta bursts followed button presses in frontal midline and somatomotor clusters, while the broad postmotor “P300” positivity summed distinct contributions from several classes of frontal, parietal, and occipital processes. The observed event-related changes in local field activities, within and between cortical areas, may serve to modulate the strength of spike-based communication between cortical areas to update attention, expectancy, memory, and motor preparation during and after target recognition and speeded responding

Conscious perception of errors and its relation to the anterior insula

To detect erroneous action outcomes is necessary for flexible adjustments and therefore a prerequisite of adaptive, goal-directed behavior. While performance monitoring has been studied intensively over two decades and a vast amount of knowledge on its functional neuroanatomy has been gathered, much less is known about conscious error perception, often referred to as error awareness. Here, we review and discuss the conditions under which error awareness occurs, its neural correlates and underlying functional neuroanatomy. We focus specifically on the anterior insula, which has been shown to be (a) reliably activated during performance monitoring and (b) modulated by error awareness. Anterior insular activity appears to be closely related to autonomic responses associated with consciously perceived errors, although the causality and directions of these relationships still needs to be unraveled. We discuss the role of the anterior insula in generating versus perceiving autonomic responses and as a key player in balancing effortful task-related and resting-state activity. We suggest that errors elicit reactions highly reminiscent of an orienting response and may thus induce the autonomic arousal needed to recruit the required mental and physical resources. We discuss the role of norepinephrine activity in eliciting sufficiently strong central and autonomic nervous responses enabling the necessary adaptation as well as conscious error perception

Neuroelectromagnetic signatures of the reproduction of supra-second durations

AbstractWhen participants are asked to reproduce an earlier presented duration, EEG recordings typically show a slow potential that develops over the fronto-central regions of the brain and is assumed to be generated in the supplementary motor area (SMA). This contingent negative variation (CNV) has been linked to anticipation, preparation and formation of temporal judgment (Macar, Vidal, and Casini, 1999, Experimental Brain Research, 125(3), 271–80). Although the interpretation of the CNV amplitude is problematic (Kononowicz and Van Rijn, (2011), Frontiers in Integrative Neuroscience, 5(48); Ng, Tobin, and Penney, 2011, Frontiers in Integrative Neuroscience, 5(77)), the observation of this slow potential is extremely robust, and thus one could assume that magnetic recordings of brain activity should show similar activity patterns. However, interval timing studies using durations shorter than one second did not provide unequivocal evidence as to whether CNV has a magnetic counterpart (CMV). As interval timing has been typically associated with durations longer than one second, participants in this study were presented intervals of 2, 3 or 4s that had to be reproduced in setup similar to the seminal work of Elbert et al. (1991, Psychophysiology, 28(6), 648–55) while co-recording EEG and MEG.The EEG data showed a clear CNV during the standard and the reproduction interval. In the reproduction interval the CNV steadily builds up from the onset of interval for both stimulus and response locked data. The MEG data did not show a CNV-resembling ramping of activity, but only showed a pre-movement magnetic field (preMMF) that originated from the SMA, occurring approximately 0.6s before the termination of the timed interval. These findings support the notion that signatures of timing are more straightforwardly measured using EEG, and show that the measured MEG signal from the SMA is constrained to the end of reproduction interval, before the voluntary movement.Moreover, we investigated a link between timing behavior and the early iCNV and late CNV amplitudes to evaluate the hypothesis that these amplitudes reflect the accumulation of temporal pulses. Larger iCNV amplitudes predicted shorter reproduced durations. This effect was more pronounced for the 2s interval reproduction, suggesting that preparatory strategies depend on the length of reproduced interval. Similarly to Elbert et al. (1991, Psychophysiology, 28(6), 648–55), longer reproductions were associated with smaller CNV amplitudes, both between conditions and across participants within the same condition. As the temporal accumulation hypothesis predicts the inverse, these results support the proposal by Van Rijn et al. (2011, Frontiers in Integrative Neuroscience, 5) that the CNV reflects other temporally driven processes such as temporal expectation and preparation rather than temporal accumulation itself

Transcranial Magnetic Stimulation Intensities in Cognitive Paradigms

BACKGROUND: Transcranial magnetic stimulation (TMS) has become an important experimental tool for exploring the brain's functional anatomy. As TMS interferes with neural activity, the hypothetical function of the stimulated area can thus be tested. One unresolved methodological issue in TMS experiments is the question of how to adequately calibrate stimulation intensities. The motor threshold (MT) is often taken as a reference for individually adapted stimulation intensities in TMS experiments, even if they do not involve the motor system. The aim of the present study was to evaluate whether it is reasonable to adjust stimulation intensities in each subject to the individual MT if prefrontal regions are stimulated prior to the performance of a cognitive paradigm. METHODS AND FINDINGS: Repetitive TMS (rTMS) was applied prior to a working memory task, either at the 'fixed' intensity of 40% maximum stimulator output (MSO), or individually adapted at 90% of the subject's MT. Stimulation was applied to a target region in the left posterior middle frontal gyrus (pMFG), as indicated by a functional magnetic resonance imaging (fMRI) localizer acquired beforehand, or to a control site (vertex). Results show that MT predicted the effect size after stimulating subjects with the fixed intensity (i.e., subjects with a low MT showed a greater behavioral effect). Nevertheless, the individual adaptation of intensities did not lead to stable effects. CONCLUSION: Therefore, we suggest assessing MT and account for it as a measure for general cortical TMS susceptibility, even if TMS is applied outside the motor domain