Louis Nahum | Université de Genève (original) (raw)

Papers by Louis Nahum

Abstract. Infrequent events, such as unexpected absence of outcomes (prediction errors), have a d... more Abstract. Infrequent events, such as unexpected absence of outcomes (prediction errors), have a detrimental effect on performance of subsequent trial in various cognitive tasks. In the present event-related potential study, we tested whether the influence of prediction error manifests itself in the early cortical processing of subsequent stimuli. Participants performed a reversal learning task in which they saw two alternating pairs of faces and indicated for each pair which one would have a declared target stimulus on its nose. The target switched to the other face after several consecutive trials with correct response, thereby inducing a prediction error, with the switch being indicated by the appearance of a disk (unexpected neutral outcome) or a spider (unexpected unpleasant outcome), depending on the condition. Results showed that after both unexpected and expected unpleasant outcomes, the amplitude of P2 decreased, while after both unexpected neutral and unpleasant outcomes, t...

Acute lesions of the posterior medial orbitofrontal cortex (OFC) in humans may induce a state of ... more Acute lesions of the posterior medial orbitofrontal cortex (OFC) in humans may induce a state of reality confusion marked by confabulation, disorientation, and currently inappropriate actions. This clinical state is strongly associated with an inability to abandon previously valid anticipations, that is, extinction capacity. In healthy subjects, the filtering of memories according to their relation with ongoing reality is associated with activity in posterior medial OFC (area 13) and electrophysiologically expressed at 220–300 ms. These observations indicate that the human OFC also functions as a generic reality monitoring system. For this function, it is presumably more important for the OFC to evaluate the current behavioral appropriateness of anticipations rather than their hedonic value. In the present study, we put this hypothesis to the test. Participants performed a reversal learning task with intermittent absence of reward delivery. High-density evoked potential analysis sho...

Hippocampus

Immediately repeated meaningful pictures in a continuous recognition task induce a positive front... more Immediately repeated meaningful pictures in a continuous recognition task induce a positive frontal potential at about 200-300 ms, which appears to emanate from the medial temporal lobe (MTL) centered on the hippocampus, as concluded from inverse solutions, coherence measurements and depth electrode recordings in humans. In this study, we tested patients with unilateral MTL lesions due to stroke to verify the provenance of this signal and its association with the spacing effect (SE) - the improved learning of material encountered in spaced rather than massed presentation. We found that unilateral left or right MTL lesions abolished the early frontal MTL-mediated signal but not the spacing effect. We conclude that the early frontal signal at 200-300 ms after immediate picture repetition may serve as a direct biomarker of MTL integrity that may be useful in the early stages of diseases like Alzheimer's. A second conclusion is that the SE does not depend on MTL integrity. This article is protected by copyright. All rights reserved.

Frontiers in behavioral neuroscience, 2017

Any thought, whether it refers to the present moment or reflects an imagination, is again encoded... more Any thought, whether it refers to the present moment or reflects an imagination, is again encoded as a new memory trace. Orbitofrontal reality filtering (ORFi) denotes an on-line mechanism which verifies whether upcoming thoughts relate to ongoing reality or not. Its failure induces reality confusion with confabulations and disorientation. If the result of this process were simultaneously encoded, it would easily explain later distinction between memories relating to a past reality and memories relating to imagination, a faculty called reality monitoring. How the brain makes this distinction is unknown but much research suggests that it depends on processes active when information is encoded. Here we explored the precise timing between ORFi and encoding as well as interactions between the involved brain structures. We used high-density evoked potentials and two runs of a continuous recognition task (CRT) combining the challenges of ORFi and encoding. ORFi was measured by the ability...

Schizophrenia research, Jan 26, 2018

A false sense of reality is a characteristic of schizophrenia spectrum disorders (SSD). Reality c... more A false sense of reality is a characteristic of schizophrenia spectrum disorders (SSD). Reality confusion may also emanate from posterior orbitofrontal cortex (OFC) lesions, as evident in confabulations that patients act upon and disorientation. This confusion can be measured by repeated runs of a continuous recognition task (CRT): patients increase their false positive rate from the second run on, failing to realize that an item is not a repetition within the current run. Correct handling of these stimuli, a faculty called orbitofrontal reality filtering (ORFi), induces a distinct frontal potential at 200-300 ms, the "ORFi potential". Patients with schizophrenia have been reported to fail in this task, too. Here, we explored the electrophysiology of ORFi in SSD. Evoked potentials, source, and connectivity analyses derived from high-density electroencephalograms of 17 patients with SSD and 15 age-matched healthy controls performing two runs of a CRT. Although the patients ...

Cortex, 2016

Behaviourally spontaneous confabulation denotes a distinct syndrome consisting of confabulations ... more Behaviourally spontaneous confabulation denotes a distinct syndrome consisting of confabulations that patients act upon, disorientation, and amnesia. It corresponds to the stable form of the original Korsakoff syndrome. While the syndrome may also occur in confusional states and degenerative dementia, this article is about the syndrome as it occurs after acute and focal brain damage. The patients act according to ideas and obligations that can mostly be traced back to real experiences in their past, but which are not currently valid guides of thinking and behaviour. This inability to abandon behavioural guides (anticipations) that are currently not valid corresponds to a failure of behavioural extinction and to the inability to abandon a previously rewarded choice in reversal learning when the expected reward (outcome) fails to occur, that is, following extinction trials. This article describes evidence from human and animal experiments showing that the posterior medial orbitofrontal cortex (OFC), which is typically damaged in these patients, and connected structures of the reward system contain the neural apparatus to signal the non-occurrence of anticipated outcomes, thereby presumably synchronizing thought and behaviour with current reality. Failure of this function, which we call orbitofrontal reality filtering, is associated with behaviourally spontaneous confabulation and disorientation after acute and focal brain damage, but not with other forms of confabulation, and not with reality confusion in degenerative dementia. Potential links with psychosis and decision making will be discussed.

Frontiers in Behavioral Neuroscience, 2016

Orbitofrontal reality filtering (ORFi) is a mechanism that allows us to keep thought and behavior... more Orbitofrontal reality filtering (ORFi) is a mechanism that allows us to keep thought and behavior in phase with reality. Its failure induces reality confusion with confabulation and disorientation. Confabulations have been claimed to have a positive emotional bias, suggesting that they emanate from a tendency to embellish the situation of a handicap. Here we tested the influence of positive emotion on ORFi in healthy subjects using a paradigm validated in reality confusing patients and with a known electrophysiological signature, a frontal positivity at 200-300 ms after memory evocation. Subjects made two continuous recognition tasks ("two runs"), composed of the same set of neutral and positive pictures, but arranged in different order. In both runs, participants had to indicate picture repetitions within, and only within, the ongoing run. The first run measures learning and recognition. The second run, where all items are familiar, requires ORFi to avoid false positive responses. High-density evoked potentials were recorded from 19 healthy subjects during completion of the task. Performance was more accurate and faster on neutral than positive pictures in both runs and for all conditions. Evoked potential correlates of emotion and reality filtering occurred at 260-350 ms but dissociated in terms of amplitude and topography. In both runs, positive stimuli evoked a more negative frontal potential than neutral ones. In the second run, the frontal positivity characteristic of reality filtering was separately, and to the same degree, expressed for positive and neutral stimuli. We conclude that ORFi, the ability to place oneself correctly in time and space, is not influenced by emotional positivity of the processed material.

Human Brain Mapping, Jul 1, 2009

Successful adaptive behavior requires fast information processing. Behavioral switches may be nec... more Successful adaptive behavior requires fast information processing. Behavioral switches may be necessary in response to threatening stimuli or when anticipated outcomes fail to occur. In this study, we explored the cortical processing of these two components using high-resolution evoked potentials. Subjects made a reversal learning task where they had to predict which one of two faces had a target stimulus on the nose. We found early electrocortical differences at 100-200 ms depending on whether the target stimulus was a spider or a disk. Source estimation indicated that this distinction was mediated by an anterior medial temporal region including the amygdala and adjacent cortex. When a switch to the alternate face was required, there was a discrete early electrocortical correlate after 200 ms, mediated by ventromedial prefrontal areas. Continued validity of stimulus-target associations was signaled at 400-520 ms, mediated by the parahippocampal region. The study indicates rapid serial processing of innate emotional quality, then cognitive-behavioral relevance of stimuli, mediated by limbic and paralimbic structures.

Journal of Psychophysiology, Apr 8, 2015

Infrequent events, such as unexpected absence of outcomes (prediction errors), have a detrimental... more Infrequent events, such as unexpected absence of outcomes (prediction errors), have a detrimental effect on performance of subsequent trial in various cognitive tasks. In the present event-related potential study, we tested whether the influence of prediction error manifests itself in the early cortical processing of subsequent stimuli. Participants performed a reversal learning task in which they saw two alternating pairs of faces and indicated for each pair which one would have a declared target stimulus on its nose. The target switched to the other face after several consecutive trials with correct response, thereby inducing a prediction error, with the switch being indicated by the appearance of a disk (unexpected neutral outcome) or a spider (unexpected unpleasant outcome), depending on the condition. Results showed that after both unexpected and expected unpleasant outcomes, the amplitude of P2 decreased, while after both unexpected neutral and unpleasant outcomes, the amplitude of P1 increased on the following presentation of the pair of faces. Source localization analysis suggested that the differences mainly emanated from the cuneus and precuneus with respect to the P1 and P2 time ranges respectively. We conclude that both the intrinsic emotional relevance of outcomes and prediction error may modulate attention allocation.

Child Neuropsychology, 2015

Orbitofrontal reality filtering denotes a memory control mechanism necessary to keep thought and ... more Orbitofrontal reality filtering denotes a memory control mechanism necessary to keep thought and behavior in phase with reality. In adults, it is mediated by the orbitofrontal cortex and subcortical connections and its failure induces reality confusion, confabulations, and disorientation. Here we investigated for the first time the development of this mechanism in 83 children from ages 7 to 11 years and 20 adults. We used an adapted version of a continuous recognition task composed of two runs with the same picture set but arranged in different order. The first run measures storage and recognition capacity (item memory), the second run measures reality filtering. We found that accuracy and reaction times in response to all stimulus types of the task improved in parallel across ages. Importantly, at no age was there a notable performance drop in the second run. This means that reality filtering was already efficacious at age 7 and then steadily improved as item memory became stronger. At the age of 11 years, reality filtering dissociated from item memory, similar to the pattern observed in adults. However, performance in 11-year-olds was still inferior as compared to adults. The study shows that reality filtering develops early in childhood and becomes more efficacious as memory capacity increases. For the time being, it remains unresolved, however, whether this function already depends on the orbitofrontal cortex, as it does in adults, or on different brain structures in the developing brains of children.

Hippocampus, 2015

Presenting stimuli again after presentation of intervening stimuli improves their retention, an e... more Presenting stimuli again after presentation of intervening stimuli improves their retention, an effect known as the spacing effect. However, using event-related potentials (ERPs), we had observed that immediate, in comparison to spaced, repetition of pictures induced a positive frontal potential at 200-300 ms. This potential appeared to emanate from the left medial temporal lobe (MTL), a structure critical for memory consolidation. In the present study, we tested the behavioral relevance of this signal and explored functional connectivity changes during picture repetition. We obtained high-density electroencephalographic (EEG) recordings from 14 healthy subjects performing a continuous recognition task where pictures were either repeated immediately or after 9 intervening items. Conventional ERP analysis replicated the positive frontal potential emanating from the left MTL at 250-350 ms in response to immediately repeated stimuli. Connectivity analysis showed that this ERP was associated with increased coherence in the MTL region - left more that right - in the theta-band (3.5-7 Hz) 200-400 ms following immediate, but not spaced, repetition. This increase was stronger in subjects who better recognized immediately repeated stimuli after 30 minutes. These findings indicate that transient theta-band synchronization between the MTL and the rest of the brain at 200-400 ms reflects a memory stabilizing signal. This article is protected by copyright. All rights reserved.

Cognitive Neuropsychiatry, 2014

Dreams might represent a window on altered states of consciousness with relevance to psychotic ex... more Dreams might represent a window on altered states of consciousness with relevance to psychotic experiences, where reality monitoring is impaired. We examined reality monitoring in healthy, non-psychotic individuals with varying degrees of dream awareness using a task designed to assess confabulatory memory errors - a confusion regarding reality whereby information from the past feels falsely familiar and does not constrain current perception appropriately. Confabulatory errors are common following damage to the ventromedial prefrontal cortex (vmPFC). Ventromedial function has previously been implicated in dreaming and dream awareness. In a hospital research setting, physically and mentally healthy individuals with high (n = 18) and low (n = 13) self-reported dream awareness completed a computerised cognitive task that involved reality monitoring based on familiarity across a series of task runs. Signal detection theory analysis revealed a more liberal acceptance bias in those with high dream awareness, consistent with the notion of overlap in the perception of dreams, imagination and reality. We discuss the implications of these results for models of reality monitoring and psychosis with a particular focus on the role of vmPFC in default-mode brain function, model-based reinforcement learning and the phenomenology of dreaming and waking consciousness.

Journal of Cognitive Neuroscience, 2015

Memory influences behavior in multiple ways. One important aspect is to remember in what precise ... more Memory influences behavior in multiple ways. One important aspect is to remember in what precise context in the past a piece of information was acquired (context source monitoring). Another important aspect is to sense whether an upcoming thought, composed of fragments of memories, refers to present reality and can be acted upon (orbitofrontal reality filtering). Whether these memory control processes share common underlying mechanisms is unknown. Failures of both have been held accountable for false memories, including confabulation. Electrophysiological and imaging studies suggest a dissociation but used very different paradigms. In this study, we juxtaposed the requirements of context source monitoring and reality filtering within a unique continuous recognition task, which healthy participants performed while high-resolution evoked potentials were recorded. The mechanisms dissociated both behaviorally and electrophysiologically: Reality filtering induced a frontal positivity, absence of a specific electrocortical configuration, and posterior medial orbitofrontal activity at 200-300 msec. Context source monitoring had no electrophysiological expression in this early period. It was slower and less accurate than reality filtering and induced a prolonged positive potential over frontal leads starting at 400 msec. The study demonstrates a hitherto unrecognized separation between orbitofrontal reality filtering and source monitoring. Whereas deficient orbitofrontal reality filtering is associated with reality confusion in thinking, the behavioral correlates of deficient source monitoring should be verified with controlled experimental exploration.

Neuroscience, 2015

Orbitofrontal reality filtering (ORF) denotes a little known but vital memory control mechanism, ... more Orbitofrontal reality filtering (ORF) denotes a little known but vital memory control mechanism, expressed at 200-300ms 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 reality confusion evident in confabulations that patients act upon and disorientation. In what way ORF differs from temporal order judgment (TOJ), that is, the conscious knowledge about when something happened in the past, has never been explored. Here we used evoked potential analysis to compare ORF and TOJ within a combined experimental 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 240-280ms, when ORF normally occurs. However, they rapidly dissociated in terms of amplitude differences and electrical source from 310 to 360ms and again from 530 to 560ms. We conclude that the task of consciously ordering memories in the immediate past (TOJ) is effortful and slow in contrast to sensing memories&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; relation with the present (ORF). Both functions invoke similar early electrocortical processes which then rapidly dissociate and engage different brain areas. The results are consistent with the different consequences of the two mechanisms&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; 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 clinical correlate.

Brain Topography, 2014

The neural correlate of anterograde amnesia in Wernicke-Korsakoff syndrome (WKS) is still debated... more The neural correlate of anterograde amnesia in Wernicke-Korsakoff syndrome (WKS) is still debated. While the capacity to learn new information has been associated with integrity of the medial temporal lobe (MTL), previous studies indicated that the WKS is associated with diencephalic lesions, mainly in the mammillary bodies and anterior or dorsomedial thalamic nuclei. The present study tested the hypothesis that amnesia in WKS is associated with a disrupted neural circuit between diencephalic and hippocampal structures. High-density evoked potentials were recorded in four severely amnesic patients with chronic WKS, in five patients with chronic alcoholism without WKS, and in ten age matched controls. Participants performed a continuous recognition task of pictures previously shown to induce a left medial temporal lobe dependent positive potential between 250 and 350 ms. In addition, the integrity of the fornix was assessed using diffusion tensor imaging (DTI). WKS, but not alcoholic patients without WKS, showed absence of the early, left MTL dependent positive potential following immediate picture repetitions. DTI indicated disruption of the fornix, which connects diencephalic and hippocampal structures. The findings support an interpretation of anterograde amnesia in WKS as a consequence of a disconnection between diencephalic and MTL structures with deficient contribution of the MTL to rapid consolidation.

Neuropsychologia, 2012

Confabulation denotes the emergence of memories of experiences and events which never took place.... more Confabulation denotes the emergence of memories of experiences and events which never took place. Whether there are distinct forms with distinct mechanisms is still debated. In this study, we explored 4 forms of confabulation and their mechanisms in 29 amnesic patients. Patients performed tests of explicit memory, executive functions, and two test of orbitofrontal reality filtering (memory selection and extinction capacity in a reversal learning task) previously shown to be strongly associated with confabulations that patients act upon and disorientation. Results indicated the following associations:

NeuroImage, 2012

Stroke lesions induce not only loss of local neural function, but disruptions in spatially distri... more Stroke lesions induce not only loss of local neural function, but disruptions in spatially distributed areas. However, it is unknown whether they affect the synchrony of electrical oscillations in neural networks and if changes in network coherence are associated with neurological deficits. This study assessed these questions in a population of patients with subacute, unilateral, ischemic stroke. Spontaneous cortical oscillations were reconstructed from high-resolution electroencephalograms (EEG) with adaptive spatial filters. Maps of functional connectivity (FC) between brain areas were created and correlated with patient performance in motor and cognitive scores. In comparison to age matched healthy controls, stroke patients showed a selective disruption of FC in the alpha frequency range. The spatial distribution of alpha band FC reflected the pattern of motor and cognitive deficits of the individual patient: network nodes that participate normally in the affected functions showed local decreases in FC with the rest of the brain. Interregional FC in the alpha band, but not in delta, theta, or beta frequencies, was highly correlated with motor and cognitive performance. In contrast, FC between contralesional areas and the rest of the brain was negatively associated with patient performance. Alpha oscillation synchrony at rest is a unique and specific marker of network function and linearly associated with behavioral performance. Maps of alpha synchrony computed from a single resting-state EEG recording provide a robust and convenient window into the functionality and organization of cortical networks with numerous potential applications.