Louis Nahum

The behavioral significance of coherent resting-state oscillations after stroke

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.

Forms of confabulation: Dissociations and associations

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: (1) Intrusions in a verbal memory test (simple provoked confabulations) dissociated from all other forms of confabulation and were not associated with any specific cognitive measure. (2) Momentary confabulations, defined as confabulatory responses to questions and measured with a confabulation questionnaire, were associated with impaired mental flexibility, a tendency to fill gaps in memory, and with one measure of reality filtering. Momentary confabulations, therefore, may emanate from diverse causes. (3) Behaviourally spontaneous confabulation, characterized by confabulations that the patients act upon and disorientation, was strongly associated with failure in the two reality filtering tasks. Behaviourally spontaneous confabulation may be seen as a specific instance of momentary confabulations with a distinct mechanism. (4) A patient producing fantastic confabulations with nonsensical, illogical content had wide-spread cognitive dysfunction and failed in the reality filtering tasks. The results support the presence of truly or partially dissociable types of confabulation with different mechanisms.

Disorientation, Confabulation, and Extinction Capacity: Clues on How the Brain Creates Reality

BACKGROUND Disorientation and confabulation often have a common course, independent of amnesia. Behaviorally spontaneous confabulation is the form in which patients act according to a false concept of reality; they fail to abandon action plans (anticipations) that do not pertain to the present situation. This continued enactment of previously valid but meanwhile invalidated anticipations can be conceived as deficient extinction capacity, that is, failure to integrate negative prediction errors into behavior. In this study, we explored whether disorientation and behaviorally spontaneous confabulation are associated with extinction failure. METHODS Twenty-five patients hospitalized for neurorehabilitation after first-ever brain injury who either had severe amnesia (n = 17), an orbitofrontal lesion (n = 14), or both (n = 6) were tested regarding disorientation (questionnaire) and performed an experimental task of association learning and extinction. Five patients were also classified as behaviorally spontaneous confabulators. RESULTS Extinction capacity explained 66% of the variance of orientation in the whole group of patients (amnesics only, 56%; orbitofrontal group only, 90%), whereas association learning explained only 17% of the variance in the whole group (amnesics only, 7%; orbitofrontal group only, 16%). Also, extinction capacity, but not association learning, significantly distinguished between behaviorally spontaneous confabulators and all other subjects. CONCLUSIONS Disorientation and behaviorally spontaneous confabulation are strongly and specifically associated with a failure of extinction, the ability to learn that previously appropriate anticipations no longer apply. Rather than invoking high-level monitoring processes, the human brain seems to make use of an ancient biological faculty-extinction-to keep thought and behavior in phase with reality.

Rapid consolidation and the human hippocampus: Intracranial recordings confirm surface EEG

Diverse studies demonstrated that although immediately repeated stimuli are better and faster recognized than stimuli repeated after a delay, this comes at the price of less‐efficient long‐term retention. A recent‐evoked potential study using source estimation of high‐resolution scalp EEG indicated that while immediate repetition induced a strikingly different electrical activity than new items in the left‐medial temporal lobe (MTL) after 200–300 ms, delayed repetition did not. In this study, we recorded evoked potentials in two epileptic patients with intracranial depth electrodes in diverse temporal and frontal areas as they performed the same task as in the previous study. We found that immediate repetition induced increase of neural activity specifically in the left MTL between 250 and 400 ms compared to new items and items repeated after a delay. The findings are important in two ways. First, they support our previous conclusion that novel information immediately initiates a consolidation process involving the left‐hippocampal area, which remains vulnerable during active maintenance and increases its effectiveness during off‐line processing. Second, they indicate that source estimation based on high‐resolution scalp EEG correctly localizes the current source of electrical activity in midline structures like the MTL.

Dopaminergic modulation of rapid reality adaptation in thinking

Dopamine has long held a prominent role in the interpretation of schizophrenia and other psychoses. Clinical studies on confabulation and disorientation, disorders marked by a confusion of reality in thinking, indicated that the ability to keep thinking in phase with reality depends on a process suppressing the interference of upcoming memories that do not refer to ongoing reality. A host of animal studies and a recent clinical study suggested that this suppression might correspond to the phasic inhibition of dopaminergic neurons in response to the absence of expected outcomes. In this study, we tested healthy subjects with a difficult version of a memory paradigm on which confabulating patients had failed. Subjects participated in three test sessions, in which they received in double-blind, randomized fashion L-dopa, risperidone, or placebo. We found that l-dopa, in comparison with risperidone, impaired performance in a highly specific way, which corresponded to the pattern of patients with reality confusion. Specifically, they had an increase of false positive responses, while overall memory performance and reaction times were unaffected. We conclude that dopaminergic transmission influences the ability to rapidly adapt thinking to ongoing reality.

Neural response to the behaviorally relevant absence of anticipated outcomes and the presentation of potentially harmful stimuli: A human fMRI study

Adaptive behavior requires the ability to react to potentially harmful stimuli, characterized by high negative inherent emotional salience (iES) (e.g., spiders, snakes), and to the unexpected non-occurrence of anticipated events. When presented simultaneously, threatening stimuli and unexpected absence of anticipated outcomes induce distinct electrocortical responses in different time periods. In this study, we used fMRI to test whether processing of the absence of anticipated outcomes (prediction errors) was anatomically dissociated from the processing of iES or whether iES simply modulated activity of areas processing the non-occurrence of anticipated outcomes. Participants saw two alternating pairs of faces and indicated for each pair which one would have a declared target stimulus on its nose. Depending on the condition, the target stimulus was either a spider (high iES stimulus) or a disk (low iES stimulus). The target stimulus switched to the other face after several consecutive correct responses, with the switch being indicated by the appearance of the alternative stimulus (disk when the spider was the declared target; spider when the disk was the declared target). We found that the spider induced stronger activation in visual areas than the disk. By contrast, the absence of anticipated outcomes specifically activated the orbitofrontal cortex (OFC), irrespective of the iES of the outcome stimulus. The findings support a generic role of the OFC in outcome monitoring.

Adaptive reorganization of cortical networks in Alzheimer's disease

OBJECTIVE The impact of neuronal cell loss associated with Alzheimers disease (AD) on the network organization of the brain is poorly understood. Here we investigated whether modifications in resting-state functional connectivity (FC) are associated with cognitive function of AD patients. METHODS High-density electroencephalograms (EEGs) were obtained from patients with early stages of AD and elderly healthy controls. Cortical oscillations were reconstructed with an adaptive spatial filter. Maps of imaginary coherence (IC) between brain areas were compared between groups and correlated with cognitive performance. RESULTS Parietal and medial temporal lobes of AD patients showed a disruption of alpha band FC to the rest of the brain. However, an adaptive extension of the language network to the right hemisphere could be observed in AD patients and was correlated with better verbal fluency. A shift of FC from alpha frequencies to theta frequencies could be observed in a memory network and was associated with better verbal memory performance. CONCLUSIONS Not only dysfunctional but also adaptive network reorganization occurs in early AD. SIGNIFICANCE The network mechanisms for preserved cognitive functioning may inform novel treatment strategies for AD in the future.

Behaviorally spontaneous confabulation in limbic encephalitis: the roles of reality filtering and strategic monitoring

Behaviorally spontaneous confabulation is characterized by a confusion of reality evident in currently inappropriate acts that patients justify with confabulations and in disorientation. Here, we describe a 38-year-old woman lawyer hospitalized because of non-herpetic, presumably autoimmune, limbic encephalitis. For months, she considered herself at work and desperately tried to respect her falsely believed professional obligations. In contrast to a completely erroneous concept of reality, she did not confabulate about her remote personal past. In tasks proposed to test strategic retrieval monitoring, she produced no confabulations. As expected, she failed in tasks of reality filtering, previously shown to have high sensitivity and specificity for behaviorally spontaneous confabulation and disorientation: she failed to suppress the interference of currently irrelevant memories and she had deficient extinction capacity. The observation underscores the special status of behaviorally spontaneous confabulation among confabulatory phenomena and of reality filtering as a thought control mechanism. We suggest that different processes may underlie the generation of false memories and their verbal expression. We also emphasize the need to present theories of confabulation together with experimental tasks that allow one to empirically verify the theories and to explore underlying physiological mechanisms.

Human Processing of Behaviorally Relevant and Irrelevant Absence of Expected Rewards: A High-Resolution ERP Study

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 showed that the omission of expected reward induced a specific electrocortical response in trials signaling the necessity to abandon the hitherto reward predicting choice, but not when omission of reward had no such connotation. This processing difference occurred at 200–300 ms. Source estimation using inverse solution analysis indicated that it emanated from the posterior medial OFC. We suggest that the human brain uses this signal from the OFC to keep thought and behavior in phase with reality.

An electrophysiological dissociation between orbitofrontal reality filtering and context source monitoring

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.