N-methyl-d-aspartate Receptor Antagonist Ketamine Impairs Action-monitoring Activity in the Prefrontal Cortex

2014 ◽  
Vol 26 (3) ◽  
pp. 577-592 ◽  
Author(s):  
Kevin Skoblenick ◽  
Stefan Everling
Keyword(s):  
Prefrontal Cortex ◽  
Error Detection ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Antisaccade Task ◽  
Self Monitoring ◽  
Action Monitoring ◽  
Aspartate Receptor ◽  
Response Errors ◽  
Monitoring Activity

Failures in monitoring of self-generated actions are thought to underlie the positive symptoms in schizophrenia. It has been hypothesized that these deficits may be caused by a dysfunction of N-methyl-d-aspartate receptors (NMDARs). Here we recorded the activity of prefrontal neurons in monkeys performing an antisaccade task, while we administered a subanesthetic dose of the noncompetitive NMDAR antagonist ketamine. Many neurons discriminated between correct antisaccades and response errors in their postresponse activity. Ketamine increased the activity for the neurons' nonpreferred response, thereby decreasing the neurons' performance selectivity. Ketamine also affected the monkeys' behavior after an error, consistent with a deficit in error detection. The results show that NMDARs play an important role in action monitoring in primates. The decrease in performance selectivity of prefrontal neurons after ketamine can help to explain the deficits in action monitoring found in humans after ketamine administration and provides support for the hypothesis that an NMDAR dysfunction underlies self-monitoring deficits and psychotic symptoms in schizophrenia.

scholarly journals Impairment of self-monitoring: part of the endophenotypic risk for psychosis

2007 ◽  
Vol 191 (S51) ◽  
pp. s58-s62 ◽  
Author(s):  
Dagmar Versmissen ◽  
Inez Myin-Germeys ◽  
Ilse Janssen ◽  
Nicolas Franck ◽  
Nicolas Georgieff ◽  
...  
Keyword(s):  
Action Recognition ◽  
Risk Group ◽  
Linear Trend ◽  
Recognition Task ◽  
Psychotic Symptoms ◽  
Control Group ◽  
Positive Symptoms ◽  
Cognitive Mechanisms ◽  
Self Monitoring ◽  
Delusional Ideation

BackgroundA disorder of self-monitoring may underlie the positive symptoms of psychosis. The cognitive mechanisms associated with these symptoms may also be detectable in individuals at risk of psychosisAimsTo investigate (a) whether patients with psychosis show impaired self-monitoring, (b) to what degree this is associated with positive symptoms, and (c) whether this is associated with liability to psychotic symptomsMethodThe sample included: individuals with a lifetime history of non-affective psychosis (n=37), a genetically defined risk group (n=41), a psychometrically defined risk group (n=40), and control group (n=49). All participants carried out an action-recognition taskResultsNumber of action – recognition errors was associated with psychosis risk (OR linear trend over 3 levels: 1.12, 95% CI 1.04–1.20) and differential error rate was associated with the degree of delusional ideation in a dose–response fashion (OR linear trend over 3 levels: 1.13, 95% CI 1.00–1.26)ConclusionsAlterations in self-monitoring are associated with psychosis with evidence of specificity for delusional ideation. In the risk state, this is expressed more as failure to recognise self-generated actions, whereas in illness failure to recognise alien sources come to the fore

scholarly journals Brain Error–monitoring Activity is Affected by Semantic Relatedness: An Event-related Brain Potentials Study

2008 ◽  
Vol 20 (5) ◽  
pp. 927-940 ◽  
Author(s):  
Lesya Y. Ganushchak ◽  
Niels O. Schiller
Keyword(s):  
Performance Monitoring ◽  
Semantic Relatedness ◽  
Lexical Retrieval ◽  
Error Monitoring ◽  
Brain Potentials ◽  
Self Monitoring ◽  
Action Monitoring ◽  
Motor Responses ◽  
Error Related Negativity ◽  
Monitoring Activity

Speakers continuously monitor what they say. Sometimes, self-monitoring malfunctions and errors pass undetected and uncorrected. In the field of action monitoring, an event-related brain potential, the error-related negativity (ERN), is associated with error processing. The present study relates the ERN to verbal self-monitoring and investigates how the ERN is affected by auditory distractors during verbal monitoring. We found that the ERN was largest following errors that occurred after semantically related distractors had been presented, as compared to semantically unrelated ones. This result demonstrates that the ERN is sensitive not only to response conflict resulting from the incompatibility of motor responses but also to more abstract lexical retrieval conflict resulting from activation of multiple lexical entries. This, in turn, suggests that the functioning of the verbal self-monitoring system during speaking is comparable to other performance monitoring, such as action monitoring.

scholarly journals Brain Structures and Cognitive Abilities Important for the Self-Monitoring of Speech Errors

2020 ◽  
Vol 1 (3) ◽  
pp. 319-338
Author(s):  
Ayan S. Mandal ◽  
Mackenzie E. Fama ◽  
Laura M. Skipper-Kallal ◽  
Andrew T. DeMarco ◽  
Elizabeth H. Lacey ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Error Detection ◽  
Cognitive Abilities ◽  
Dorsolateral Prefrontal Cortex ◽  
Brain Structures ◽  
Auditory Comprehension ◽  
Self Monitoring ◽  
Word Level ◽  
Frontal White Matter ◽  
Dorsolateral Prefrontal

The brain structures and cognitive abilities necessary for successful monitoring of one’s own speech errors remain unknown. We aimed to inform self-monitoring models by examining the neural and behavioral correlates of phonological and semantic error detection in individuals with post-stroke aphasia. First, we determined whether detection related to other abilities proposed to contribute to monitoring according to various theories, including naming ability, fluency, word-level auditory comprehension, sentence-level auditory comprehension, and executive function. Regression analyses revealed that fluency and executive scores were independent predictors of phonological error detection, while a measure of word-level comprehension related to semantic error detection. Next, we used multivariate lesion-symptom mapping to determine lesion locations associated with reduced error detection. Reduced overall error detection related to damage to a region of frontal white matter extending into dorsolateral prefrontal cortex. Detection of phonological errors related to damage to the same areas, but the lesion-behavior association was stronger, suggesting that the localization for overall error detection was driven primarily by phonological error detection. These findings demonstrate that monitoring of different error types relies on distinct cognitive functions, and provide causal evidence for the importance of frontal white matter tracts and the dorsolateral prefrontal cortex for self-monitoring of speech.

Evaluation of positive and negative symptoms in schizophrenia

1986 ◽  
Vol 1 (2) ◽  
pp. 108-122 ◽  
Author(s):  
Nancy C. Andreasen ◽  
William M. Grove
Keyword(s):  
Negative Symptoms ◽  
The United States ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
University Of Iowa ◽  
Normal Functions ◽  
Subsequent Investigation ◽  
The University ◽  
The Relationship ◽  
Positive And Negative Symptoms

SummaryMost investigators concur that schizophrenia is probably a heterogeneous group of disorders that share the common features of psychotic symptoms, partial response to neuroleptics, and a relatively poor outcome. The subdivision of schizophrenia into two subtypes, positive versus negative, has achieved wide acceptance throughout the world during recent years. This distinction has heuristic and theoretical appeal because it unites phenomenology, pathophysiology, and etiology into a single comprehensive hypothesis.In spite of its wide appeal, the distinction has a number of problems. These include the failure to distinguish between symptom syndromes and diseases; failure to deal with the mixed patient; failure to take longitudinal course into account; and failure to address conceptually and methodologically the distinction between positive and negative symptoms.This paper focuses primarily on the conceptual basis for two instruments designed to measure positive and negative symptoms, the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS), originally described in 1982. Since their description, these scales have been used in a variety of other centers. These scales are based on the hypothesis that negative symptoms represent a deficit or diminution in normal psychological functions wliile positive symptoms represent an excess or distortion of normal functions. Reliability data are now available from Italy, Spain, and Japan which suggest that these scales can be used reliably in cultural settings outside the United States. The results of these studies are summarized in this paper. In addition, a replication study involving a new sample of 117 schizophrenics collected at the University of Iowa is described. In this second study of the SANS and SAPS, internal consistency is found to be quite high in the SANS. Thus negative symptoms appear to be more internally correlated with one another than are positive symptoms. The implications of this result are discussed. A principal components analysis is used to explore the relationship between positive and negative symptoms. While the study reported in 1982 suggested that positive and negative symptoms are negatively correlated, in the present study they appear to be uncorrelated. Overall, the results suggest that the SANS and SAPS are useful comprehensive instruments for the evaluation of positive and negative symptoms. The relationship between these symptoms and external validators such as cognitive functioning or CT scan abnormalities will be reported in a subsequent investigation.

Self-monitoring in speech production: effects of verbal hallucinations and negative symptoms

1994 ◽  
Vol 24 (3) ◽  
pp. 749-761 ◽  
Author(s):  
I. Leudar ◽  
P. Thomas ◽  
M. Johnston
Keyword(s):  
Speech Production ◽  
Error Detection ◽  
Negative Symptoms ◽  
Self Monitoring ◽  
Acoustic Feedback ◽  
Production Effects ◽  
Internal Error

SynopsisThis paper reports results of a study on self-monitoring in speech production. Thirty schizophrenics, varying in verbal hallucination and in negative symptoms status, and 17 controls were tested on the reporter test. The position of interruptions of the speech-flow to repair errors was used to indicate whether the detection of the errors was through monitoring of internal phonetic plans or through external acoustic feedback. We have found that the internal error detection was twice as frequent in controls as in schizophrenics. The relevance of this finding to Frith's (1992) model of schizophrenia is discussed. Our conclusion is that the problem with internal monitoring of phonetic plans is common to all schizophrenics, and not just to those with verbal hallucinations.

ARE SOME TYPES OF PSYCHOTIC SYMPTOMS MORE RESPONSIVE TO COGNITIVE-BEHAVIOUR THERAPY?

2001 ◽  
Vol 29 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Nicholas Tarrier ◽  
Caroline Kinney ◽  
Ellis McCarthy ◽  
Anja Wittkowski ◽  
Lawrence Yusupoff ◽  
...  
Keyword(s):  
Cognitive Behaviour Therapy ◽  
Negative Symptoms ◽  
Controlled Trial ◽  
Chronic Schizophrenia ◽  
Routine Care ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Behaviour Therapy ◽  
Cognitive Behaviour ◽  
Supportive Counselling

Results are presented from a randomized controlled trial indicating which psychotic symptoms respond to cognitive behaviour therapy. The aim of the study was to investigate whether different types of psychotic symptoms are more or less responsive to cognitive-behaviour therapy compared to treatment received by control groups. Seventy-two patients suffering from chronic schizophrenia who experienced persistent positive psychotic symptoms were assessed at baseline and randomized to either cognitive-behaviour therapy and routine care, supportive counselling and routine care, or routine care alone and were re-assessed after 3 months of treatment (post-treatment). Independent and blind assessment of outcome indicated delusions significantly improved with both cognitive behaviour therapy and supportive counselling compared to routine care. Hallucinations significantly decreased with cognitive-behaviour therapy compared to supportive counselling. There was no difference in the percentage change of hallucinations compared to delusions in patients treated by cognitive behaviour therapy. There was little change in measures of affective symptoms but there was no evidence that a reduction in positive symptoms was associated with an increase in depres sion. In fact, a reduction in positive symptoms was positively correlated with a reduction in depression. There were significant differences in the reductions in thought disorder and negative symptoms with an advantage of cognitive-behaviour therapy compared to routine care.

scholarly journals Cognitive–behavioural therapy for refractory psychotic symptoms of schizophrenia resistant to atypical antipsychotic medication

2005 ◽  
Vol 186 (4) ◽  
pp. 324-330 ◽  
Author(s):  
Lucia R. Valmaggia ◽  
Mark van der Gaag ◽  
Nicholas Tarrier ◽  
Marieke Pijnenborg ◽  
Cees J. Slooff
Keyword(s):  
Cognitive Behavioural Therapy ◽  
Rating Scale ◽  
Behavioural Therapy ◽  
Controlled Study ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Cognitive Behavioural ◽  
Supportive Counselling ◽  
Treatment Refractory

BackgroundThere is increasing evidence that cognitive–behavioural therapy can be an effective intervention for patients experiencing drug-refractory positive symptoms of schizophrenia.AimsTo investigate the effects of cognitive–behavioural therapy on in-patients with treatment-refractory psychotic symptoms.MethodManualised therapy was compared with supportive counselling in a randomised controlled study. Both interventions were delivered by experienced psychologists over 16 sessions of treatment. Therapy fidelity was assessed by two independent raters. Participants underwent masked assessment at baseline, after treatment and at 6 months' follow-up. Main outcome measures were the Positive and Negative Syndrome Scale and the Psychotic Symptoms Rating Scale. The analysis was by intention to treat.ResultsParticipants receiving cognitive–behavioural therapy had improved with regard to auditory hallucinations and illness insight at the post-treatment assessment, but these findings were not maintained at follow-up.ConclusionsCognitive–behavioural therapy showed modest short-term benefits over supportive counselling for treatment-refractory positive symptoms of schizophrenia.

scholarly journals Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Amira Ben Afia ◽  
Èlia Vila ◽  
Karina S. MacDowell ◽  
Aida Ormazabal ◽  
Juan C. Leza ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
High Performance ◽  
Interaction Analysis ◽  
Kynurenine Pathway ◽  
Psychotic Symptoms ◽  
Post Mortem ◽  
Control Subjects ◽  
Network Interaction ◽  
Hydroxyindoleacetic Acid ◽  
Cortical Circuit

Abstract Background The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). Methods This work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. Results In the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. Conclusions Thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.

Sign in / Sign up

Export Citation Format

Share Document