scholarly journals LSD impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision making

2019 ◽  
Author(s):  
Thomas Pokorny ◽  
Patricia Duerler ◽  
Erich Seifritz ◽  
Franz X. Vollenweider ◽  
Katrin H. Preller
Keyword(s):  
Decision Making ◽  
Working Memory ◽  
Executive Functions ◽  
Cognitive Flexibility ◽  
Spatial Working Memory ◽  
Neuropsychological Test ◽  
Memory Task ◽  
Double Blind ◽  
Receptor System

AbstractPsychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied. Therefore, we examined the acute effects of LSD (100µg) alone and in combination with the 5-HT2A antagonist ketanserin (40mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery. Compared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT2A antagonist ketanserin normalized all LSD-induced cognitive deficits. The present findings highlight the role of the 5-HT2A receptor system in executive functions and working memory and suggest that specific 5-HT2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.

scholarly journals LSD acutely impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision-making

2019 ◽  
Vol 50 (13) ◽  
pp. 2255-2264 ◽  
Author(s):  
Thomas Pokorny ◽  
Patricia Duerler ◽  
Erich Seifritz ◽  
Franz X. Vollenweider ◽  
Katrin H. Preller
Keyword(s):  
Decision Making ◽  
Working Memory ◽  
Executive Functions ◽  
Cognitive Flexibility ◽  
Spatial Working Memory ◽  
Neuropsychological Test ◽  
Memory Task ◽  
Double Blind ◽  
Receptor System

AbstractBackgroundPsychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision-making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied.MethodsWe examined the acute effects of LSD (100 µg) alone and in combination with the 5-HT2A antagonist ketanserin (40 mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery.ResultsCompared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence the quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT2A antagonist ketanserin normalized all LSD-induced cognitive deficits.ConclusionsThe present findings highlight the role of the 5-HT2A receptor system in executive functions and working memory and suggest that specific 5-HT2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.

scholarly journals Acute anxiety and autonomic arousal induced by CO2 inhalation impairs prefrontal executive functions in healthy humans

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
George Savulich ◽  
Frank H. Hezemans ◽  
Sophia van Ghesel Grothe ◽  
Jessica Dafflon ◽  
Norah Schulten ◽  
...  
Keyword(s):  
Working Memory ◽  
Executive Functions ◽  
Cognitive Flexibility ◽  
Emotional Processing ◽  
Spatial Working Memory ◽  
Neuropsychological Test ◽  
Memory Task ◽  
Autonomic Arousal ◽  
Healthy Humans ◽  
Acute Anxiety

Abstract Acute anxiety impacts cognitive performance. Inhalation of air enriched with carbon dioxide (CO2) in healthy humans provides a novel experimental model of generalised anxiety, but has not previously been used to assess cognition. We used inhalation of 7.5% CO2 to induce acute anxiety and autonomic arousal in healthy volunteers during neuropsychological tasks of cognitive flexibility, emotional processing and spatial working memory in a single-blind, placebo-controlled, randomized, crossover, within-subjects study. In Experiment 1 (n = 44), participants made significantly more extra-dimensional shift errors on the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional Set Shift task under CO2 inhalation compared with ‘normal’ air. Participants also had slower latencies when responding to positive words and made significantly more omission errors for negative words on the CANTAB Affective Go/No-go task. In Experiment 2 (n = 28), participants made significantly more total errors and had poorer heuristic search strategy on the CANTAB Spatial Working Memory task. In both experiments, CO2 inhalation significantly increased negative affect; state anxiety and fear; symptoms of panic; and systolic blood pressure/heart rate. Overall, CO2 inhalation produced robust anxiogenic effects and impaired fronto-executive functions of cognitive flexibility and working memory. Effects on emotional processing suggested a mood-congruent slowing in processing speed in the absence of a negative attentional bias. State-dependent effects of anxiety on cognitive-emotional interactions in the prefrontal cortex warrant further investigation.

scholarly journals Maternal depression and trajectories of child internalizing and externalizing problems: the roles of child decision making and working memory

2016 ◽  
Vol 47 (6) ◽  
pp. 1138-1148 ◽  
Author(s):  
E. Flouri ◽  
A. Ruddy ◽  
E. Midouhas
Keyword(s):  
Decision Making ◽  
Working Memory ◽  
Maternal Depression ◽  
Risk Taking ◽  
Internalizing Problems ◽  
Externalizing Problems ◽  
Spatial Working Memory ◽  
Neuropsychological Test ◽  
Memory Task ◽  
Poor Quality

BackgroundMaternal depression may affect the emotional/behavioural outcomes of children with normal neurocognitive functioning less severely than it does those without. To guide prevention and intervention efforts, research must specify which aspects of a child's cognitive functioning both moderate the effect of maternal depression and are amenable to change. Working memory and decision making may be amenable to change and are so far unexplored as moderators of this effect.MethodOur sample was 17 160 Millennium Cohort Study children. We analysed trajectories of externalizing (conduct and hyperactivity) and internalizing (emotional and peer) problems, measured with the Strengths and Difficulties Questionnaire at the ages 3, 5, 7 and 11 years, using growth curve models. We characterized maternal depression, also time-varying at these ages, by a high score on the K6. Working memory was measured with the Cambridge Neuropsychological Test Automated Battery Spatial Working Memory Task, and decision making (risk taking and quality of decision making) with the Cambridge Gambling Task, both at age 11 years.ResultsMaternal depression predicted both the level and the growth of problems. Risk taking and poor-quality decision making were related positively to externalizing and non-significantly to internalizing problems. Poor working memory was related to both problem types. Neither decision making nor working memory explained the effect of maternal depression on child internalizing/externalizing problems. Importantly, risk taking amplified the effect of maternal depression on internalizing problems, and poor working memory that on internalizing and conduct problems.ConclusionsImpaired decision making and working memory in children amplify the adverse effect of maternal depression on, particularly, internalizing problems.

scholarly journals Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making

2021 ◽  
Author(s):  
Kei Oyama ◽  
Yukiko Hori ◽  
Yuji Nagai ◽  
Naohisa Miyakawa ◽  
Koki Mimura ◽  
...  
Keyword(s):  
Decision Making ◽  
Working Memory ◽  
Neural Circuits ◽  
Spatial Working Memory ◽  
Memory Task ◽  
Projection Mapping ◽  
Impaired Performance ◽  
Brain Functions ◽  
Neuronal Projection

The primate prefrontal cortex (PFC) is situated at the core of higher brain functions by linking and cooperating with the caudate nucleus (CD) and mediodorsal thalamus (MD) via neural circuits. However, the distinctive roles of these prefronto-subcortical pathways remain elusive. Combining in vivo neuronal projection mapping with chemogenetic synaptic silencing, we reversibly dissected key pathways from PFC to the CD and MD individually in single monkeys. We found that silencing the bilateral PFC-MD projections, but not the PFC-CD projections, impaired performance in a spatial working memory task. Conversely, silencing the unilateral PFC-CD projection, but not the PFC-MD projection, altered preference in a free-choice task. These results revealed dissociable roles of the prefronto-subcortical pathways in working memory and decision-making, representing the technical advantage of imaging-guided pathway-selective chemogenetic manipulation for dissecting neural circuits underlying cognitive functions in primates.

scholarly journals Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making

2021 ◽  
Vol 7 (26) ◽  
pp. eabg4246
Author(s):  
Kei Oyama ◽  
Yukiko Hori ◽  
Yuji Nagai ◽  
Naohisa Miyakawa ◽  
Koki Mimura ◽  
...  
Keyword(s):  
Decision Making ◽  
Working Memory ◽  
Neural Circuits ◽  
Spatial Working Memory ◽  
Memory Task ◽  
Mediodorsal Thalamus ◽  
Projection Mapping ◽  
Impaired Performance ◽  
Brain Functions

The primate prefrontal cortex (PFC) is situated at the core of higher brain functions via neural circuits such as those linking the caudate nucleus and mediodorsal thalamus. However, the distinctive roles of these prefronto-subcortical pathways remain elusive. Combining in vivo neuronal projection mapping with chemogenetic synaptic silencing, we reversibly dissected key pathways from dorsolateral part of the PFC (dlPFC) to the dorsal caudate (dCD) and lateral mediodorsal thalamus (MDl) individually in single monkeys. We found that silencing the bilateral dlPFC-MDl projections, but not the dlPFC-dCD projections, impaired performance in a spatial working memory task. Conversely, silencing the unilateral dlPFC-dCD projection, but not the unilateral dlPFC-MDl projection, altered preference in a decision-making task. These results revealed dissociable roles of the prefronto-subcortical pathways in working memory and decision-making, representing the technical advantage of imaging-guided pathway-selective chemogenetic manipulation for dissecting neural circuits underlying cognitive functions in primates.

scholarly journals Executive functions are impaired in adolescents engaging in non-suicidal self-injury

2010 ◽  
Vol 41 (3) ◽  
pp. 601-610 ◽  
Author(s):  
L. T. Fikke ◽  
A. Melinder ◽  
N. I. Landrø
Keyword(s):  
Working Memory ◽  
Executive Functions ◽  
Spatial Working Memory ◽  
Neuropsychological Test ◽  
Group Differences ◽  
Control Group ◽  
High Severity ◽  
Self Injury ◽  
Diagnostic Characteristics ◽  
Males And Females

BackgroundThe aim of this study was to investigate three main aspects of executive functions (EFs), i.e. shifting, updating and inhibition, in adolescents engaging in non-suicidal self-injury (NSSI) as compared with healthy controls.MethodEFs were assessed using the Intra/Extradimensional Set Shift, the Spatial Working Memory (SWM) Test and the Stop Signal Test (SST) from the Cambridge Neuropsychological Test Automated Battery (CANTAB), in a high-severity NSSI group (n=33), a low-severity NSSI group (n=29) and a healthy control group (n=35). Diagnostic characteristics were examined using the Kiddie-Sads-Present and Lifetime Version.ResultsThere were group differences on the SWM Test. A trend towards an interaction effect of sex revealed that males in the high-severity NSSI group made significantly more errors than males and females in the control group. Both males and females in the high-severity NSSI group made poor use of an efficient strategy in completing the test. The low-severity NSSI group performed poorly on the SST, making more errors than the control group and showing an impaired ability to inhibit initiated responses, as compared with the high-severity NSSI group. There were group differences in frequencies of current and previous major depressive disorder. However, no effects of these diagnoses were found on any of the EF tests.ConclusionsThis study demonstrates that NSSI subgroups have distinct deficits in EFs. The high-severity NSSI group has working memory deficits, while the low-severity NSSI group has impaired inhibitory control. This supports the emotion regulation hypothesis.

scholarly journals Reading in developmental dyslexia: the role of phonemic awareness and executive functions

2021 ◽  
Vol 38 ◽  
Author(s):  
Giovanna Beatriz Kalva MEDINA ◽  
Sandra Regina Kirchner GUIMARÃES
Keyword(s):  
Working Memory ◽  
Executive Functions ◽  
Cognitive Flexibility ◽  
Phonemic Awareness ◽  
Developmental Dyslexia ◽  
Verbal Fluency ◽  
Reading Difficulties ◽  
Reading Performance ◽  
Spearman Test

Abstract This study investigated the correlations and the possible deficits in reading, phonemic awareness, and executive functions among students with developmental dyslexia. A total of 28 students participated in the study, between 9 and 11 years old, 14 with developmental dyslexia and 14 without reading difficulties. Specific instruments were used to assess reading, phonemic awareness, and executive functions. The Spearman test indicated moderate and very significant correlations between performance in tasks of phonemic awareness and reading (recognition and comprehension) and tasks that assessed cognitive functioning involving the following executive functions: cognitive flexibility, working memory, inhibitory control, and orthographic verbal fluency. No correlation was found between the reading and phonemic awareness assessments and the results of the planning done with the Tower of London instrument. The results allowed the researchers to hypothesize that an intervention planned for the development of phonemic awareness and executive functions may have an effect in improving the reading performance of dyslexics.

Imaging the Networks of Executive Functions

2016 ◽  
Author(s):  
Christen M. Holder ◽  
Nicole Shay
Keyword(s):  
Decision Making ◽  
Working Memory ◽  
Executive Function ◽  
Executive Functions ◽  
Cognitive Flexibility ◽  
Processing Speed ◽  
Temporal Lobes ◽  
Memory Inhibition ◽  
Lesion Studies ◽  
The Right

This chapter examines the different theoretical conceptualizations of executive functions and how neuroimaging can reveal their neuroanatomical mechanisms. After briefly considering various definitions and descriptions of executive function, it discusses the results of lesion studies that look into specific executive functions; namely, attention, working memory, inhibition, decision-making, planning and organization, processing speed, and cognitive flexibility or shifting. It also evaluates measures that are used to capture the executive functions just cited, along with the advances that have been achieved with the help of neuroimaging studies. On the basis of neuroimaging evidence, the authors show that the right prefrontal cortex, as well as the parietal and temporal lobes, plays an important role in executive function.

scholarly journals Eye Movements in the “Morris Maze” Spatial Working Memory Task Reveal Deficits in Strategic Planning

2019 ◽  
Vol 31 (4) ◽  
pp. 497-509 ◽  
Author(s):  
Timothy L. Hodgson ◽  
Frouke Hermens ◽  
Kyla Pennington ◽  
Jade S. Pickering ◽  
Gemma Ezard ◽  
...  
Keyword(s):  
Working Memory ◽  
Eye Movements ◽  
Parkinson Disease ◽  
Spatial Working Memory ◽  
Neuropsychological Test ◽  
Memory Task ◽  
Disease Symptoms ◽  
Measure Of Performance ◽  
Foraging Task ◽  
Healthy Participants

Analysis of eye movements can provide insights into processes underlying performance of cognitive tasks. We recorded eye movements in healthy participants and people with idiopathic Parkinson disease during a token foraging task based on the spatial working memory component of the widely used Cambridge Neuropsychological Test Automated Battery. Participants selected boxes (using a mouse click) to reveal hidden tokens. Tokens were never hidden under a box where one had been found before, such that memory had to be used to guide box selections. A key measure of performance in the task is between search errors (BSEs) in which a box where a token has been found is selected again. Eye movements were found to be most commonly directed toward the next box to be clicked on, but fixations also occurred at rates higher than expected by chance on boxes farther ahead or back along the search path. Looking ahead and looking back in this way was found to correlate negatively with BSEs and was significantly reduced in patients with Parkinson disease. Refixating boxes where tokens had already been found correlated with BSEs and the severity of Parkinson disease symptoms. It is concluded that eye movements can provide an index of cognitive planning in the task. Refixations on locations where a token has been found may also provide a sensitive indicator of visuospatial memory integrity. Eye movement measures derived from the spatial working memory task may prove useful in the assessment of executive functions as well as neurological and psychiatric diseases in the future.

Working Memory and Number Sense as Predictors of Mathematical (Dis-)Ability

2015 ◽  
Vol 223 (2) ◽  
pp. 102-109 ◽  
Author(s):  
Evelyn H. Kroesbergen ◽  
Marloes van Dijk
Keyword(s):  
Working Memory ◽  
Learning Disabilities ◽  
Spatial Working Memory ◽  
Number Sense ◽  
Mathematical Learning ◽  
Visual Spatial ◽  
Mathematical Learning Disabilities ◽  
Visual Spatial Working Memory ◽  
And Mathematics

Recent research has pointed to two possible causes of mathematical (dis-)ability: working memory and number sense, although only few studies have compared the relations between working memory and mathematics and between number sense and mathematics. In this study, both constructs were studied in relation to mathematics in general, and to mathematical learning disabilities (MLD) in particular. The sample consisted of 154 children aged between 6 and 10 years, including 26 children with MLD. Children performing low on either number sense or visual-spatial working memory scored lower on math tests than children without such a weakness. Children with a double weakness scored the lowest. These results confirm the important role of both visual-spatial working memory and number sense in mathematical development.

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