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

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.

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

10.1101/2021.02.01.429248 ◽

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.

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

Psychological Medicine ◽

10.1017/s0033291716003226 ◽

2016 ◽

Vol 47 (6) ◽

pp. 1138-1148 ◽

Cited By ~ 5

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.

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

Psychological Medicine ◽

10.1017/s0033291719002393 ◽

2019 ◽

Vol 50 (13) ◽

pp. 2255-2264 ◽

Cited By ~ 6

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.

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

10.1101/532234 ◽

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.

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Brain hemodynamic response in Examiner–Examinee dyads during spatial short-term memory task: an fNIRS study

Experimental Brain Research ◽

10.1007/s00221-021-06073-0 ◽

2021 ◽

Author(s):

Francesco Panico ◽

Stefania De Marco ◽

Laura Sagliano ◽

Francesca D’Olimpio ◽

Dario Grossi ◽

...

Keyword(s):

Working Memory ◽

Cognitive Processes ◽

Short Term Memory ◽

Spatial Working Memory ◽

Brain Activity ◽

Memory Task ◽

Neural Correlates ◽

Short Term ◽

Term Memory ◽

The Real

AbstractThe Corsi Block-Tapping test (CBT) is a measure of spatial working memory (WM) in clinical practice, requiring an examinee to reproduce sequences of cubes tapped by an examiner. CBT implies complementary behaviors in the examiners and the examinees, as they have to attend a precise turn taking. Previous studies demonstrated that the Prefrontal Cortex (PFC) is activated during CBT, but scarce evidence is available on the neural correlates of CBT in the real setting. We assessed PFC activity in dyads of examiner–examinee participants while completing the real version of CBT, during conditions of increasing and exceeding workload. This procedure allowed to investigate whether brain activity in the dyads is coordinated. Results in the examinees showed that PFC activity was higher when the workload approached or reached participants’ spatial WM span, and lower during workload conditions that were largely below or above their span. Interestingly, findings in the examiners paralleled the ones in the examinees, as examiners’ brain activity increased and decreased in a similar way as the examinees’ one. In the examiners, higher left-hemisphere activity was observed suggesting the likely activation of non-spatial WM processes. Data support a bell-shaped relationship between cognitive load and brain activity, and provide original insights on the cognitive processes activated in the examiner during CBT.

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Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance

Psychological Medicine ◽

10.1017/s0033291702007018 ◽

2003 ◽

Vol 33 (3) ◽

pp. 455-467 ◽

Cited By ~ 177

Author(s):

F. C. MURPHY ◽

A. MICHAEL ◽

T. W. ROBBINS ◽

B. J. SAHAKIAN

Keyword(s):

Working Memory ◽

Negative Feedback ◽

Performance Feedback ◽

Visual Discrimination ◽

Negative Reinforcement ◽

Spatial Working Memory ◽

Memory Task ◽

Depressive Illness ◽

Reversal Task ◽

Depressed Patients

Background. Recent evidence suggests that an abnormal response to performance feedback may contribute to the wide-ranging neuropsychological deficits typically associated with depressive illness. The present research sought to determine whether the inability of depressed patients to utilize performance feedback advantageously is equally true for accurate and misleading feedback.Method. Patients with major depression and matched controls completed: (1) a visual discrimination and reversal task that featured intermittent and misleading negative feedback; and (2) feedback and no-feedback versions of a computerised test of spatial working memory. In the feedback version, negative feedback was accurate, highly informative, and could be used as a mnemonic aid.Results. On the Probability Reversal task, depressed patients were impaired in their ability to maintain response set in the face of misleading negative feedback as shown by their increased tendency to switch responding to the ‘incorrect’ stimulus following negative reinforcement, relative to that of controls. Patients' ability to acquire and reverse the necessary visual discrimination was unimpaired. On the Spatial Working Memory task, depressed patients made significantly more between-search errors than controls on the most difficult trials, but their ability to use negative feedback to facilitate performance remained intact.Conclusions. The present results suggest that feedback can have different effects in different contexts. Misleading, negative feedback appears to disrupt the performance of depressed patients, whereas negative but accurate feedback does not. These findings are considered in the context of recent studies on reinforcement systems and their associated neurobiological substrates.

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Reproducibility of fMRI Results across Four Institutions Using a Spatial Working Memory Task

NeuroImage ◽

10.1006/nimg.1998.0360 ◽

1998 ◽

Vol 8 (3) ◽

pp. 249-261 ◽

Cited By ~ 158

Author(s):

B.J. Casey ◽

Jonathan D. Cohen ◽

Kathy O'Craven ◽

Richard J. Davidson ◽

William Irwin ◽

...

Keyword(s):

Working Memory ◽

Spatial Working Memory ◽

Memory Task

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Phenomenology of Visuo-spatial Working Memory Task Performance

10.31231/osf.io/5843r ◽

2021 ◽

Author(s):

Aleš Oblak ◽

Anka Slana Ozimič ◽

Grega Repovš ◽

Urban Kordeš

Keyword(s):

Working Memory ◽

Cognitive Psychology ◽

Task Performance ◽

Present Article ◽

Spatial Working Memory ◽

Memory Task ◽

Bodily Feelings ◽

Psychological Tasks

In experimental cognitive psychology, objects of inquiry have typically been operationalized with psychological tasks. If we are interested in measuring the target phenomena, we must inquire into the validity of the task; that is, to what extent does the task elicit the phenomenon in question. If we subscribe to the second view, evaluating the validity and the interpretation of the gathered data can be supplemented by understanding the experience of solving psychological tasks. The aim of the present article is to investigate how individuals experience performing a psychological task, specifically, a visuo-spatial working memory task. We present ethnographic descriptions of different ways individuals can experience the same task. We focus on aspects of experience that comprise the overall sense of experience (e.g., bodily feelings, emotional atmosphere, mood). We discuss the methodological implications of our findings and the possibility of conducting a neurophenomenology of visuo-spatial working memory.

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Declined functional connectivity of white matter during rest and working memory tasks associates with cognitive impairments in schizophrenia

10.1101/2020.05.16.20091397 ◽

2020 ◽

Cited By ~ 1

Author(s):

Yurui Gao ◽

Muwei Li ◽

Anna S Huang ◽

Adam W Anderson ◽

Zhaohua Ding ◽

...

Keyword(s):

Working Memory ◽

White Matter ◽

Functional Connectivity ◽

Resting State ◽

Spatial Working Memory ◽

Cognitive Impairments ◽

Memory Task ◽

Brain Network ◽

Blood Oxygenation ◽

Cerebral Peduncle

BACKGROUND: Schizophrenia, characterized by cognitive impairments, arises from a disturbance of brain network. Pathological changes in white matter (WM) have been indicated as playing a role in disturbing neural connectivity in schizophrenia. However, deficits of functional connectivity (FC) in individual WM bundles in schizophrenia have never been explored; neither have cognitive correlates with those deficits. METHODS: Resting-state and spatial working memory task fMRI images were acquired on 67 healthy subjects and 84 patients with schizophrenia. The correlations in blood-oxygenation-level-dependent (BOLD) signals between 46 WM and 82 gray matter regions were quantified, analyzed and compared between groups under three scenarios (i.e., resting state, retention period and entire time of a spatial working memory task). Associations of FC in WM with cognitive assessment scores were evaluated for three scenarios. RESULTS: FC deficits were significant (p<.05) in external capsule, cingulum, uncinate fasciculus, genu and body of corpus callosum under all three scenarios. Deficits were also present in the anterior limb of the internal capsule and cerebral peduncle in task scenario. Decreased FCs in specific WM bundles associated significantly (p<.05) with cognitive impairments in working memory, processing speed and/or cognitive control. CONCLUSIONS: Decreases in FC are evident in several WM bundles in patients with schizophrenia and are significantly associated with cognitive impairments during both rest and working memory tasks. Furthermore, working memory tasks expose FC deficits in more WM bundles and more cognitive associates in schizophrenia than resting state does.

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Negative Effects of Embodiment in a Visuo-Spatial Working Memory Task in Children, Young Adults, and Older Adults

Frontiers in Psychology ◽

10.3389/fpsyg.2021.688174 ◽

2021 ◽

Vol 12 ◽

Author(s):

Gianluca Amico ◽

Sabine Schaefer

Keyword(s):

Older Adults ◽

Working Memory ◽

Young Adults ◽

Spatial Information ◽

Spatial Working Memory ◽

Cognitive Task ◽

Memory Performance ◽

Age Groups ◽

Memory Task ◽

Negative Effects

Studies examining the effect of embodied cognition have shown that linking one’s body movements to a cognitive task can enhance performance. The current study investigated whether concurrent walking while encoding or recalling spatial information improves working memory performance, and whether 10-year-old children, young adults, or older adults (Mage = 72 years) are affected differently by embodiment. The goal of the Spatial Memory Task was to encode and recall sequences of increasing length by reproducing positions of target fields in the correct order. The nine targets were positioned in a random configuration on a large square carpet (2.5 m × 2.5 m). During encoding and recall, participants either did not move, or they walked into the target fields. In a within-subjects design, all possible combinations of encoding and recall conditions were tested in counterbalanced order. Contrary to our predictions, moving particularly impaired encoding, but also recall. These negative effects were present in all age groups, but older adults’ memory was hampered even more strongly by walking during encoding and recall. Our results indicate that embodiment may not help people to memorize spatial information, but can create a dual-task situation instead.

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