Effects of Lorazepam on the Neuromagnetic Mismatch Negativity (MMNm) and Auditory Evoked Field Component N100m

Abstract

The mismatch negativity (MMN) as an auditory evoked potential is thought to reflect an early, preconscious attention process. While this component has gained great importance in studies on clinical populations and in basic research on auditory information processing, the involvement of different neurotransmitters in the generation of this component is less well understood. We investigated the impact of the benzodiazepine lorazepam as a GABA agonist on the neuromagnetic MMN (MMNm) and auditory evoked field component N100m. A group of 12 healthy subjects was studied in single blind trials under the following three conditions: after the intake of 1.25 mg lorazepam, 100 mg caffeine or placebo. Neuromagnetic recordings were obtained before drug intake and three times after it. Controlled visual attention was tested additionally using a version of the Continuous Performance Test (CPT). The neuromagnetic activity was reconstructed by a single moving dipole, and the dipole moment and its latency were compared between conditions and time points of measurement. Lorazepam diminished the signal detection performance in the CPT 25 min after drug intake. The source of the field component N100m was attenuated, most significantly in the recording 105 min after lorazepam intake. The attenuation of the MMNm under lorazepam became significant at 105 min, but was visually less apparent, because in all conditions a decrease of the MMNm dipole moment within the course of a session was observed. Besides the already known effects of benzodiazepines on controlled attention functions, preconscious attention functions as reflected in the MMN are impaired by acute benzodiazepine intake. MMN studies on clinical populations have to be controlled for the recording time because of the strong habituation of this component.

The effect of methylphenidate on auditory information processing in healthy volunteers: a combined EEG/MEG study

“…The important role of the GABA system in modulating MMN responses was showed by Smolnik et al (1998), who reported an increase in MMN amplitudes after the administration of benzodiazepine flumazenil. Rosburg et al (2004) also confirmed a relation between GABA and MMN by showing an increase in MMN latency under the effect of lorazepam. As the reduction in MMNm amplitude after scopolamine administration suggests, the cholinergic system could modulate MMN as well (Pekkonen et al 2001(Pekkonen et al , 2005.…”

Acute dopamine D1 and D2 receptor stimulation does not modulate mismatch negativity (MMN) in healthy human subjects

“…While there is strong support for the role of NMDA receptors in modulating MMN, the studies investigating the role of other neurochemical systems, including the dopaminergic (Kähkönen et al 2001Pekkonen et al 2002), serotonergic Umbricht et al 2002Umbricht et al , 2003Kähkönen et al 2005), cholinergic (Inami et al 2005;Baldeweg et al 2006;Knott et al 2006a, b), GABAergic (Nakagome et al 1998;Smolnik et al 1998;Rosburg et al 2004) and histaminergic (Serra et al 1996) systems have demonstrated inconsistent findings. Thus, the effects of other neurotransmitter systems on MMN generation warrant further investigation.…”

Hippocampal event-related potentials to tone duration deviance in a passive oddball paradigm in humans

“…Intracranial data were compared with simultaneously recorded data from the scalp. Finally, all data were screened for a possible occurrence of long-term habituation, as previous studies have shown a response decrease of the MMN within experiments (McGee et al, 2001;Rosburg et al, 2004).…”