Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers

Abstract

The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.

Effects of the 5-HT2A Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Performance Task: Implications for the Neuropharmacology of Cognitive Deficits in Schizophrenia

“…In nonhuman primates, NMDAR antagonists selectively abolish the generation of MMN without affecting sensory ERPs such as N1 (Javitt et al, 1992(Javitt et al, , 1994(Javitt et al, , 1996. Likewise, we recently demonstrated that the NMDAR antagonist ketamine induces a significant reduction of MMN, but not of N1, in healthy volunteers (Umbricht et al, 2000). Similarly, ketamine and other NMDAR antagonists significantly reduced MMNm (the magnetic counterpart of MMN) and MMN, respectively, in healthy volunteers (Jääskeläinen et al, 1995a(Jääskeläinen et al, , b, 1996Kreitschmann-Andermahr et al, 2001;Pang and Fowler, 1999).…”

“…Similarly, ketamine and other NMDAR antagonists significantly reduced MMNm (the magnetic counterpart of MMN) and MMN, respectively, in healthy volunteers (Jääskeläinen et al, 1995a(Jääskeläinen et al, , b, 1996Kreitschmann-Andermahr et al, 2001;Pang and Fowler, 1999). In addition, subanesthetic doses of ketamine induce a pattern of deficits in AX-CPT performance in healthy volunteers that is characterized by a specific increase of context-dependent (BX) errors and closely resembles the deficits observed in schizophrenia (Umbricht et al, 2000). Thus, the available evidence suggests that in schizophrenia NMDAR-related dysfunction may contribute significantly to abnormalities in context-dependent information processing both at preattentive automatic and at attention-dependent controlled levels.…”

“…The primary aim of this study was to investigate the effects of a 5-HT 2A agonist, psilocybin, on the generation of MMN and sensory ERPs and on AX-CPT performance in healthy volunteers using identical test procedures as used previously in our ketamine study (Umbricht et al, 2000) and to address the potential role of the 5-HT 2A receptor in both these cognitive operations. We wanted to investigate if dysfunctional 5-HT 2A receptor-dependent neurotransmission might also contribute to deficits in MMN generation and AX-CPT performance, and thus address the hypothesis that abnormalities of this receptor may play a role in comparable deficits in schizophrenia.…”

Subchronic Continuous Phencyclidine Administration Potentiates Amphetamine-Induced Frontal Cortex Dopamine Release

“…These agents uniquely induce symptoms resembling the negative and disorganized symptoms of schizophrenia and produce schizophrenia-like information processing deficits by interacting with cortical NMDA receptors (Krystal et al, 1994;Lahti et al, 1995;Malhotra et al, 1996;Umbricht et al, 2000). However, it remains unknown whether NMDA receptor dysfunction, of itself, would be sufficient to account for the dopaminergic hyperactivity associated with the disorder.…”

Mismatch negativity is not correlated with neuroendocrine indicators of catecholaminergic activity in healthy subjects

“…Few data are available concerning the influence of neurotransmitter systems on the MMN. In a single-blind placebo-controlled study, Umbricht et al (2000) have suggested that N-methyl-D-aspartate receptors (NMDAR) were critically involved in the human MMN because the NMDAR antagonist keta-mine significantly decreased the peak amplitude of the MMN. These results indicated that glutamatergic activity could be involved in the genesis of the MMN.…”