Safety and risk assessment of psychedelic psychotherapy: A meta-analysis and systematic review.

Psychotherapies assisted by psychedelic substances have shown promising results in the treatment of psychiatric disorders. The aim of this systematic review and meta-analysis was to evaluate safety data in human subjects. We carried out a search on MEDLINE, Embase and PsycINFO databases between 2000 and 2022. Standardized mean differences between different dose ranges and between acute and subacute phases were calculated for cardiovascular data after psychedelic administration. Risk differences were calculated for serious adverse events and common side effects. Thirty studies were included in this meta-analysis. There were only nine serious adverse events for over 1000 administrations of psychedelic substances (one during the acute phase and 8 during the post-acute phase). There were no suicide attempts during the acute phase and 3 participants engaged in self-harm during the post-acute phase. There was an increased risk for elevated heart rate, systolic and diastolic blood pressure for all dose range categories, as well as an increased risk of nausea during the acute phase. Other common side effects included headaches, anxiety, and decreased concentration or appetite. This meta-analysis demonstrates that psychedelics are well-tolerated, with a low risk of emerging serious adverse events in a controlled setting with appropriate inclusion criteria.

The benefits of mind wandering on a naturalistic prospective memory task.

Mind wandering (MW) occurs when our attention spontaneously shifts from the task at hand to inner thoughts. MW is often future-oriented and may help people remember to carry out their planned actions (Prospective Memory, PM). Past-oriented MW might also play a critical role in boosting PM performance. Sixty participants learned 24 PM items and recalled them during an immersive virtual walk in a town. The items were divided into event-based-EB and time-based-TB. During the PM retention phase, participants were randomly assigned to a high or a low cognitive load condition, in order to manipulate MW frequency. Some PM items were encoded before this MW manipulation (pre-PM) and some during the virtual walk (post-PM). A high MW frequency was linked with better global PM performances. Spontaneous past-oriented MW predicted better pre-EB retrospective PM retrieval, while spontaneous future-oriented MW predicted better Pre-EB prospective PM retrieval. Voluntary future-oriented MW predicted better post-EB retrospective retrieval. We highlighted, for the first time, a differential impact of spontaneous MW content depending on the PM component (retrospective or prospective). Past-oriented MW is crucial for (re)consolidating PM intentions, and episodic future thinking MW for the execution of PM intentions. We discuss the twofold functional role of MW, namely, to consolidate an already programmed intention and to plan future actions.

Impact of a Naturalistic Psychedelic Experience on Smoking: A Retrospective Survey.

Tobacco use disorder is a major public health concern. The aim of this study was to investigate the impact of a psychedelic experience in a natural context on tobacco use. A retrospective online survey was conducted on 173 individuals who reported having had a psychedelic experience while being smokers. Demographic information was collected, and characteristics of the psychedelic experience, tobacco addiction and psychological flexibility were assessed. Mean number of cigarettes smoked per day, and proportion of individuals with high tobacco dependency significantly decreased between the three time points (p < .001). Participants who reduced or quit smoking had more intense mystical experiences during the psychedelic session (p = .01) and lower psychological flexibility before the psychedelic experience (p = .018). The increase in psychological flexibility post psychedelic session, and the personal motives for the psychedelic experience were significant positive predictors of smoking reduction or cessation (p < .001). Our results confirmed that a psychedelic experience in smoker individuals can be associated with smoking and tobacco dependency reduction and that the personal motives for the psychedelic session, the intensity of the mystical experience, and the increase of psychological flexibility following the psychedelic experience, are associated with smoking cessation or reduction.

The role of temporal distance of the events on the spatiotemporal dynamics of mental time travel to one's personal past and future.

Mental time travel to personal past and future events shows remarkable cognitive and neural similarities. Both temporalities seem to rely on the same core network involving episodic binding and monitoring processes. However, it is still unclear in what way the temporal distance of the simulated events modulates the recruitment of this network when mental time-travelling to the past and the future. The present study explored the electrophysiological correlates of remembering and imagining personal events at two temporal distances from the present moment (near and far). Temporal distance modulated the late parietal component (LPC) and the late frontal effect (LFE), respectively involved in episodic and monitoring processes. Interestingly, temporal distance modulations differed in the past and future event simulation, suggesting greater episodic processing for near as opposed to far future situations (with no differences on near and far past), and the implementation of greater post-simulation monitoring processes for near past as compared to far past events (with high demands on both near and far future). These findings show that both past and future event simulations are affected by the temporal distance of the events, although not exactly in a mirrored way. They are discussed according to the increasing role of semantic memory in episodic mental time travel to farther temporal distances from the present.

Physiological investigation of cognitive load in real-life train travelers during information processing.

Management of travelers' cognitive load is crucial for efficient information processing for optimal railway operations. We investigated variations in travelers' cognitive load with different expertise levels, in a field study. We aimed to assess the use of three eye metrics: pupil diameter, saccade amplitude and gaze of fixation duration for cognitive load analysis between expert and novice travelers in a Mass Transit train station: Saint-Michel Notre Dame. Physiological measures of emotional activity through skin conductance responses were also investigated, together with subjective measures of mental load using NASA-Task Load Index. Our results followed our expectations, where novice travelers expressed higher cognitive load than expert travelers, characterized by wider pupil diameter, larger amplitude of saccade and longer gaze duration, as well as higher electrodermal activity and NASA-TLX. Additional observations showed that experts used hierarchical and symmetrical scan paths, with more intense exposure on relevant information, characterized by brighter heat maps. This difference in behavior showed a clear difference in strategies for information retrieval at different expertise levels. Metrics of eye tracking device, together with electrodermal activity, proved to be potent in cognitive load analysis of train travelers, and helped to provide insights for real-life information processing.

Neuropsychological improvement after posterior fossa arachnoid cyst drainage.

PURPOSE: Posterior fossa arachnoid cysts (PFAC) are mostly considered as benign lesions of the cerebellum. Although many studies have shown the major role of the cerebellum in modulating movement, language, cognition, and social interaction, there are few studies on the cognitive impact and surgical decompression of PFAC. METHODS: We present the cases of two brothers successively diagnosed with PFAC and neuropsychological delay. After multidisciplinary discussion with the boys' parents, it was decided to drain these lesions. Clinical signs, cerebral images, and neuropsychological status were assessed on admission and then 1 and 3 years after surgery. RESULTS: At presentation, both children had mild cerebellar signs, associated with cognitive and visual-motor impairments and academic regression. CT scans revealed retrovermian cysts, which were shunted. Post-operatively, both brothers demonstrated improved visual-motor skills and behavior. At follow-up, we observed disappearance of dysarthria and academic delay and significant improvement in cognition especially at the intelligence scale and in language. Fine motor skills had improved but remained slower than the average and writing skills appeared limited. CONCLUSION: Except for PFAC which impair cerebrospinal fluid circulation or which are responsible for a significant mass effect, most PFAC are usually considered as "asymptomatic" and do not require surgical treatment. The two cases reported herein suggest that these lesions might be responsible for some associated but potentially reversible neuropsychological impairment. In the future, clinical assessment should include neuropsychological evaluation to help inform decision for surgical decompression in these children with PFAC.

Mechanisms of remembering the past and imagining the future--new data from autobiographical memory tasks in a lifespan approach.

We investigated the episodic/semantic distinction in remembering the past and imagining the future and explored cognitive mechanisms predicting events' specificity throughout the lifespan. Eighty-three 6- to 81-year-old participants, divided into 5 age groups, underwent past, present and future episodic (events' evocation) and semantic (self-descriptions) autobiographical tasks and a complementary cognitive test battery (executive functions, working and episodic memory). The main results showed age effects on episodic events' evocation indicating an inverted U function (i.e., developmental progression from 6 to 21years and aging decline). By contrast, age effects were slighter on self-descriptions while self-defining events' evocation increased with age. Furthermore, age effects on episodic events' evocation were mainly mediated by age effects on cognitive functions and personal semantics. These new findings indicate a developmental and aging episodic/semantic distinction for both remembering the past and imagining the future, and suggest that above similarities, these abilities could have a fundamentally different basis.

Using virtual reality to characterize episodic memory profiles in amnestic mild cognitive impairment and Alzheimer's disease: influence of active and passive encoding.

Most neuropsychological assessments of episodic memory bear little similarity to the events that patients actually experience as memories in daily life. The first aim of this study was to use a virtual environment to characterize episodic memory profiles in an ecological fashion, which includes memory for central and perceptual details, spatiotemporal contextual elements, and binding. This study included subjects from three different populations: healthy older adults, patients with amnestic mild cognitive impairment (aMCI) and patients with early to moderate Alzheimer's disease (AD). Second, we sought to determine whether environmental factors that can affect encoding (active vs. passive exploration) influence memory performance in pathological aging. Third, we benchmarked the results of our virtual reality episodic memory test against a classical memory test and a subjective daily memory complaint scale. Here, the participants were successively immersed in two virtual environments; the first, as the driver of a virtual car (active exploration) and the second, as the passenger of that car (passive exploration). Subjects were instructed to encode all elements of the environment as well as the associated spatiotemporal contexts. Following each immersion, we assessed the patient's recall and recognition of central information (i.e., the elements of the environment), contextual information (i.e., temporal, egocentric and allocentric spatial information) and lastly, the quality of binding. We found that the AD patients' performances were inferior to that of the aMCI and even more to that of the healthy aged groups, in line with the progression of hippocampal atrophy reported in the literature. Spatial allocentric memory assessments were found to be particularly useful for distinguishing aMCI patients from healthy older adults. Active exploration yielded enhanced recall of central and allocentric spatial information, as well as binding in all groups. This led aMCI patients to achieve better performance scores on immediate temporal memory tasks. Finally, the patients' daily memory complaints were more highly correlated with the performances on the virtual test than with their performances on the classical memory test. Taken together, these results highlight specific cognitive differences found between these three populations that may provide additional insight into the early diagnosis and rehabilitation of pathological aging. In particular, neuropsychological studies would benefit to use virtual tests and a multi-component approach to assess episodic memory, and encourage active encoding of information in patients suffering from mild or severe age-related memory impairment. The beneficial effect of active encoding on episodic memory in aMCI and early to moderate AD is discussed in the context of relatively preserved frontal and motor brain functions implicated in self-referential effects and procedural abilities.

Autonoetic consciousness in autobiographical memories after medial temporal lobe resection.

This study aims to investigate autonoetic consciousness associated with episodic autobiographical memory in patients who had undergone unilateral medial temporal lobe resection for intractable epilepsy. Autonoetic consciousness, defined as the conscious feeling of mentally travelling back in time to relive a specific event, was assessed using the Remember/Know (R/K) paradigm across different time periods as proposed in the autobiographical memory task developed by Piolino et al. (TEMPau task). Results revealed that the two patient groups (left and right temporal resection) gave reduced sense of reliving (R) responses and more familiarity (K) responses than healthy controls. This poor autonoetic consciousness was highlighted when patients were asked to justify their Remember responses by recalling sensory-perceptive, affective or spatiotemporal specific details across all life periods. These results support the bilateral MTL contribution to episodic autobiographical memory covering the entire lifespan, which is consistent with the multiple trace theory of MTL function. This study also demonstrates the bilateral involvement of MTL structures in recalling specific details of personal events characterized by autonoetic consciousness.

Autobiographical memory after temporal lobe resection: neuropsychological and MRI volumetric findings.

This study examined the contribution of medial temporal lobe (MTL) structures in autobiographical memory. While some investigators have reported a temporal gradient in memory performance, characterized by retrieval difficulties limited to recent periods of life [Squire and Alvarez (Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr Opin Neurobiol 1995; 5: 169-77)], others have suggested that this impairment involves all life-time periods [Nadel and Moscovitch (Memory consolidation, retrograde amnesia and the hippocampal complex. Curr Opin Neurobiol 1997; 7: 217-27)]. In this study, autobiographical memory was assessed in 22 patients who had undergone a left (n = 12) or a right (n = 10) MTL resection for the relief of epileptic seizures and in 22 normal control participants. For this purpose, we used an autobiographical memory task (TEMPau, Piolino et al., 2003) across four time periods covering the subjects' entire lifespan. For each period, an overall autobiographical memory score (AM score) was obtained, from which a strictly episodic score (SE score), characterized by specificity and richness of details, was computed. For all events recalled, Remember responses justified by specificity of factual, spatial and temporal contents (jR responses) were measured using the Remember/Know paradigm. MRI volumetric analyses performed on the medial (i.e. hippocampus, temporopolar, entorhinal, perirhinal and parahippocampal cortices) and lateral temporal (i.e. superior, middle and inferior temporal gyri) lobe structures stated that the resection mainly included MTL structures. AM and SE scores were impaired in patients with right and left MTL resections as compared to normal controls across all time periods, reflecting the patients' particular difficulty in producing specific and detailed memories across all periods. This impairment was associated with poor autonoetic consciousness, revealed by the small number of jR responses across all periods. Results of correlation analysis between MRI volume measures of temporal lobe structures and autobiographical memory scores suggest that the right MTL structures are particularly responsive in reliving the encoding context regardless of remoteness. Our results support the bilateral MTL contribution to episodic autobiographical memory covering the entire lifespan, which is consistent with the multiple trace theory of MTL function [Moscovitch et al. (Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory. J Anat 2005; 207: 35-66.)].

Do school-age children remember or know the personal past?

The aim of this study was to examine developmental differences in autobiographical memory using a novel test that assesses its semantic and episodic subcomponents. Forty-two children aged 7-13 years were asked to recall semantic information and episodic events from three different time periods (current school year, last school year, and previous school years). For the recalls of all events, sense of remembering or sense of just knowing was measured via the Remember/Know paradigm. Age-related differences were observed for episodic autobiographical memory whereas semantic autobiographical memory was characterized by a relative developmental invariance. The increase with age was also found in the number of "Remember" responses and their justification in terms of the actual contextual information retrieved-factual, spatial, and, more especially, temporal details. These findings highlight developmental differences between the episodic and semantic subcomponents of autobiographical memory and support the view that mental 'time travel' through subjective time, which allows one to re-experience the past through self-awareness, is the last feature of autobiographical memory to become fully operational.

[Episodic autobiographical memory in depression: a review]. / Mémoire autobiographique épisodique et dépression.

INTRODUCTION: Autobiographical memory and personal identity (self) are linked by a reciprocal relationship. Autobiographical memory is critical for both grounding and changing the self. Individuals' current self-views, beliefs, and goals influence their recollections of the past. According to Tulving, episodic memory is characterized by autonoetic consciousness, which is associated with a sense of the self in the past (emotions and goals) and mental reliving of an experience. Its close relationship with self and emotion strongly involves episodic autobiographical memory in the psychopathology of depression. However, due to methodological and conceptual issues, little attention has been paid to episodic autobiographical memory in depression. Since the seminal work of Williams et al. 15 years ago, there is now growing interest around this issue. LITERATURE FINDINGS: We reviewed the evidence for three major features of autobiographical memory functioning in depression: an increase in general memory retrieval (overgenerality), a mood-congruent memory effect and the high occurrence of intrusive memories of stressful events. Although it was first observed among suicidal patients, overgenerality is actually associated with both depression and post-traumatic stress disorder. Overgenerality is not associated with anxious disorders other than post-traumatic stress disorder, obsessive-compulsive disorder, or borderline personality disorder. Most of controlled studies carried out on autobiographical memory in depression rely on the Williams' Autobiographical Memory Test (AMT). When presented with positive and negative cue words and asked to retrieve specific personal events, depressed patients (unlike matched controls) are less specific in their memories. They tend to recall repeated events (categorical overgeneral memories) rather than single episodes (specific memories). Overgenerality in depression is: 1) more evident with positive than with negative events (mood-congruent memory effect); 2) related to avoidance of intrusive memories; 3) quite stable over time, ie, remaining after remission; and 4) related to short-term prognosis in depression. Although it is not clear whether overgenerality is a cause or an effect of depression, there is some evidence to suggest that overgenerality is a trait marker indicating vulnerability to persistent depression. Mood-congruent effect, a well-known effect in depression, has been addressed in both autobio-graphical and non-autobiographical memory. Depressed patients spontaneously recall more negative than positive memories. With the AMT, depressed patients take longer to respond to positive than to negative cues, whereas controls do the opposite. Depression is also associated with a high occurrence of spontaneous intrusive memories of stressful life events. Studies found intrusions and related avoidance, as measured by the Impact of Event Scale, to be positively correlated with overgenerality, whereas there was no direct link between performance on the Autobiographical Memory Test and stressful life events per se. Both Williams' mnemonic interlock model and Conway's self-memory system are useful models to address the complexity of findings regarding autobiographical memory and depression. DISCUSSION: According to Williams, repeated avoidance of stressful memories leads depressed patients to have an autobiographical memory functioning characterized by iterative retrievals of categorical overgeneral memories, producing an enduring overgeneral retrieval style. According to Conway, the recollection of autobiographical memories requires a retrieval process that provides access to sensory/perceptual event-specific knowledge (ie perceptions and feelings) via a personal semantic knowledge base (ie lifetime periods and generic events). This retrieval process (generative retrieval mode) relies on both executive functioning and current self-view, namely the working-self. Spontaneous memories, usually vivid, result from a direct retrieval mode in which event-specific knowledge is directly triggered. In line with this model, episodic autobiographical memory impairment in state depression may arise from the working self rather than from autobiographical knowledge. The mood-congruent effect may be explained by the current (depressed) self. The high occurrence of intrusive memories may be explained by lack of executive control during direct retrieval. Overgenerality may rely on the interaction of both executive dysfunction and current (depressed) self, within the working-self, during generative retrieval. Our review suggests that further evidence is needed to address the relationship between executive functioning, self and autobiographical memory in depression.

[Alzheimer's disease and human memory]. / La maladie d'Alzheimer et la mémoire humaine.

Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way with eminently changing memory representations.

Long-term memory following transient global amnesia: an investigation of episodic and semantic memory.

BACKGROUND: Several studies noted persistence of memory impairment following an episode of transient global amnesia (TGA) with standard tests. AIM: To specify long-term memory impairments in a group of patients selected with stringent criteria. METHODS: Both retrograde and anterograde memory were investigated in 32 patients 13-67 months after a TGA episode with original tasks encompassing retrograde semantic memory (academic, public and personal knowledge), retrograde episodic memory (autobiographical events) and anterograde episodic memory. RESULTS: Patients had preserved academic and public knowledge. Pathological scores were obtained in personal verbal fluency for the two most recent periods, and patients produced less autobiographical events than controls. However, when they were provided time to detail, memories were as episodic as in controls regardless of their remoteness. Anterograde episodic tasks revealed a mild but significant impairment of the capacity of re-living the condition of encoding, i.e. the moment at which words were presented. CONCLUSIONS: Patients who have suffered from an episode of TGA manifest deficits of memory focused on the retrieval of both recent semantic information and episodic memories and especially the capacity of re-living. These deficits may not result from a deterioration of memory per se but rather from difficulties in accessing memories.

The dynamic time course of memory recovery in transient global amnesia.

AIMS: To investigate the dynamic time course of transient global amnesia (TGA)--that is, the process of recovery and the interindividual variability--by testing four patients during the day of TGA itself (on three occasions) and at follow up (on two occasions). METHODS: A specially designed protocol focusing on semantic (both conceptual and autobiographical knowledge) and episodic (both anterograde and retrograde components) memory. RESULTS: Every patient showed marked impairment of both anterograde and retrograde episodic memory during the acute phase, with a relative preservation of personal and conceptual semantic knowledge. During the following phase, the authors observed similarities and differences among the patients' patterns of recovery. In general, retrograde amnesia recovered before the anterograde amnesia and anterograde episodic memory was recovered gradually in every case. In contrast, shrinkage of retrograde amnesia was more heterogeneous. In two of the patients, this shrinkage followed a chronological gradient and the most remote events were recovered first. In the two other patients, it depended more on the strength of the trace, and there was no temporal gradient. For the latter, an executive deficit could account for difficulties in accessing both conceptual knowledge and autobiographical memories. CONCLUSIONS: This profile of recovery suggests a "neocortical to medial temporal" process in every case, and the possibility of an additional frontal dysfunction in some cases. Hence, the acute phase seems to be characterised by a common episodic impairment. This variability between subjects appears in the recovery phase with two different patterns of impairment.

[Contribution of positron emission tomography to functional neuroimaging in Alzheimer's disease]. / Contribution de la tomographie par émission de positons à la neuro-anatomie fonctionnelle de la maladie d'Alzheimer.

When combined with cognitive investigations, functional neuroimaging methods such as positron emission tomography allow to depict the neural substrates that underlie the neuropsychological alterations in Alzheimer's disease. Capitalising on the variance in both cognitive performances and resting cerebral metabolic rate of glucose (CMRGlc) in Alzheimer's disease, it is possible to correlate these two quantitative variables on a pixel-by-pixel basis and to generate maps showing the significant correlations in stereotaxic space. Some examples using this approach in the domain of memory disorders are presented in this brief review. We notably show that the localisation of the significant correlations differs from one memory system to another, as evaluated by clinical memory tasks. This approach also unravels the compensatory mechanisms that take place with evolution of the disease. Over and above its interest in clinical neuropsychology, this method constitutes a new source of inferences complementary to the classic activation paradigm in normal subjects, as the latter identifies the cerebral structures that are involved with, but not necessarily indispensable for, the normal execution of the task. This approach highlights the interest of combining functional neuroimaging and neuropsychology to better understand the neural substrates of cognitive deficits in both patients with memory disorders and elderly normal subjects.

[Functional neuroanatomy of the autobiographical memory]. / Neuroanatomie fonctionnelle de la mémoire autobiographique.

Autobiographical memory refers to events and information about personal life and the self. Within autobiographical memory, many authors make a difference between episodic and semantic components. Study of retrograde amnesia gives information about memory consolidation. According to the "standard model" of consolidation, the medial temporal lobe plays a time-limited role in retrieval memory. Functional neuroanatomy studies of autobiographical memory are very few and many are recent. These studies concern which brain regions are involved in the autobiographical retrieval, episodic or semantic autobiographical memory and consolidation process. Results show that autobiographical retrieval depends on specific brain regions like frontal cortex. Concerning memory consolidation, findings are most consistent with the idea that hippocampal complex is involved in both recent and remote memories.

[The assessment of episodic memory: theory and practice]. / L'évaluation de la mémoire épisodique: théorie et pratique.

Episodic memory refers to a system which stores personally experienced events located in time and in space. It is characterized by autonoetic consciousness allowing a subject to be aware of his/her own identity throughout subjective time and to perceive the present as both a continuation of his/her past and as a prelude to his/her future. Current studies of episodic memory should take into account all these features. However, most episodic memory tests are restricted to memory performance and do not really measure episodic memory. In this article, after defining the terms of context and states of awareness, we describe two original tasks designed specially to investigate episodic memory: the 'Quoi-Où-Quand' (What-Where-When) and the 'TEMPau'. The first task allows the study of anterograde amnesia whereas the second consists of an assessment of retrograde amnesia. These two tasks include both scores of memory performance and measures of states of awareness using a procedure derived from the Remember/Know paradigm.