MEMORY IN TIME: ELECTROPHYSIOLOGICAL COMPARISON BETWEEN REALITY FILTERING AND TEMPORAL ORDER JUDGMENT M. C. LIVERANI, a A. L. MANUEL, a A. BOUZERDA-WAHLEN, a M. GENETTI, b A. G. GUGGISBERG, a,c L. NAHUM a AND A. SCHNIDER a,c * a Laboratory of Cognitive Neurorehabilitation, Medical School, University of Geneva, Switzerland b Department of Fundamental Neurosciences, University of Geneva, Switzerland c Division of Neurorehabilitation, Department of Clinical Neurosciences, University Hospital and University of Geneva, Switzerland Abstract—Orbitofrontal reality filtering (ORF) denotes a little known but vital memory control mechanism, expressed at 200–300 ms after stimulus presentation, that allows one to sense whether evoked memories (thoughts) refer to present reality and can be acted upon, or not. Its failure induces real- ity confusion evident in confabulations that patients act upon and disorientation. In what way ORF differs from tem- poral order judgment (TOJ), that is, the conscious knowl- edge about when something happened in the past, has never been explored. Here we used evoked potential analy- sis to compare ORF and TOJ within a combined experimen- tal task and within a comparable time frame, close to the experienced present. Seventeen healthy human subjects performed an experiment using continuous recognition tasks that combined the challenges of ORF and TOJ. We found that the two mechanisms dissociated behaviorally: subjects were markedly slower and less accurate in TOJ than ORF. Both mechanisms evoked similar potentials at 240–280 ms, when ORF normally occurs. However, they rap- idly dissociated in terms of amplitude differences and elec- trical source from 310 to 360 ms and again from 530 to 560 ms. We conclude that the task of consciously ordering memories in the immediate past (TOJ) is effortful and slow in contrast to sensing memories’ relation with the present (ORF). Both functions invoke similar early electrocortical processes which then rapidly dissociate and engage differ- ent brain areas. The results are consistent with the different consequences of the two mechanisms’ dysfunction: while failure of ORF has a known clinical manifestation (reality confusion as evident in confabulation and disorientation), the failure of TOJ, as tested here, has no such known clini- cal correlate. Ó 2015 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: reality filtering, orbitofrontal cortex, source memory, temporal order judgment, evoked potentials, time. INTRODUCTION The experience of remembering is fundamental to human action and thinking. A crucial aspect of memory is time. Two capacities are clearly important: the ability to sense whether a memory (thought) pertains to present reality – and may be acted upon – and the ability to recollect the temporal context in which a memory was acquired. An impairment of the former capacity is associated with reality confusion, as evident in disorientation and confabulations that patients act upon (Schnider, 2008, 2013). For example, a 58-year-old woman left the exam- ination convinced that she had to feed her baby – who was 35 years old at the time (Schnider, 1996); a dentist hospitalized after rupture of an aneurysm of the anterior communicating artery repeatedly left the hospital in the conviction that patients were waiting for him at his clinic (Ptak and Schnider, 1998). Schnider and colleagues explained this kind of behavior by the failure of a specific mechanism they now call orbitofrontal reality filtering (ORF) (Schnider, 2008, 2013). They found that, when reality confusing patients made repeated runs of a contin- uous recognition task, all of them composed by the same picture set, they produced increasingly more false positive responses, in contrast to correctly oriented amnesics (Schnider et al., 1996a; Schnider and Ptak, 1999; Nahum et al., 2012). Healthy subjects performing such a task had activation of the posterior orbitofrontal cortex and subcortical structures (Schnider et al., 2000; Treyer et al., 2003), which corresponds to the main lesion site of reality confusing patients (Schnider et al., 1996a; Schnider and Ptak, 1999; Schnider, 2013). Successful completion of the task by healthy subjects was associated with a frontal positivity in evoked potential responses at 200–300 ms, indicating that reality filtering (RF) occurs before the content of an upcoming thought or memory is processed at 400–600 ms (Schnider et al., 2002; Wahlen et al., 2011; Schnider, 2013). ORF bears superficial resemblance to well-known memory-monitoring models. Strategic retrieval describes http://dx.doi.org/10.1016/j.neuroscience.2014.12.064 0306-4522/Ó 2015 IBRO. Published by Elsevier Ltd. All rights reserved. * Correspondence to: A. Schnider, Service de Neurore´e´ducation, Hoˆpitaux Universitaires de Gene`ve, 26, Avenue de Beau-Se´jour, CH-1211 Geneva 14, Switzerland. Tel: +41-22-372-3700; fax: +41-22- 372-3705. E-mail address: armin.schnider@hcuge.ch (A. Schnider). Abbreviations: ANOVA, analysis of variance; DRF, distracters within the reality filtering task; DTJ, distracters within the temporal judgment task; EEG, Electroencephalography; ERPs, event-related potentials; LAURA, local auto-regressive average; ORF, orbitofrontal reality filtering; RF, reality filtering; ROI, region of interest; TANOVA, topographic analysis of variance; TJ, temporal judgment; TOJ, temporal order judgment; TRF, targets within the reality filtering task; TTJ, targets within the temporal judgment task. Neuroscience 289 (2015) 279–288 279