Adler LE, Hoffer LJ, Griffith J, Waldo MC, Freedman R. Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry 32: 607-616
ABSTRACT Diminished gating of the P50 auditory evoked response to repeated stimuli is a psychophysiological feature of schizophrenia, that is also present in many relatives of patients. Animal models of auditory sensory gating indicate that nicotinic cholinergic neurotransmission is a critical neuronal substrate. The aim of this experiment was to determine if the deficit in sensory gating could be reversed by nicotine administration. Nonsmoking relatives of schizophrenics with abnormal sensory gating were selected as subjects for this initial double-blind trial, to avoid effects of psychotropic medications that might complicate trials in schizophrenic patients themselves. Nicotine-containing gum increased P50 sensory gating to near normal levels within 30 min of administration. The effect was transient; the gating of P50 returned to baseline levels within 1 hr. There was no change observed after placebo administration. In one of the subjects, the anticholinesterase inhibitor physostigmine similarly normalized P50 gating. The results are consistent with the hypothesis that nicotinic cholinergic neurotransmission may mediate a familial psychophysiological deficit in schizophrenia.
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- "Pharmacological challenge studies have been informative about neurotransmitters involved in this kind of response suppression and emphasized the role of nicotinic acetylcholine receptors (Adler et al., 1992, 1993; Turetsky et al., 2012; Knott et al., 2013). Furthermore, studies using electroencephalography (EEG), magnetoencephalography (MEG), electrocorticography (ECoG), and fMRI provided some knowledge about brain structures that form the neural network underlying the processing of such auditory stimuli. "
ABSTRACT: To assess whether the response decrement of auditory evoked potentials (AEPs) after stimulus repetition is affected by an interplay between sensitization and habituation. AEPs were recorded in 18 healthy participants. Stimulation consisted of trains with eight tones. The 6th stimulus of each train was a frequency deviant. The N100 amplitude to the 1st stimulus of the train was quantified in each trial. Trials with initially strong N100 responses and with initially weak N100 responses were averaged separately. For the total trial sample, the N100 and P200 amplitudes decreased from the 1st to the 2nd stimulus of the train but not thereafter. Trials with an initially strong N100 response were qualified by likewise larger N100 amplitudes to the 2nd stimulus, as compared to trials with initially weak N100 responses, and were characterized by a pronounced N100 amplitude decrease from standards to deviants. Our findings are difficult to reconcile with the view that the response decrement of AEP components after stimulus repetition is modulated by sensitization and habituation, as no evidence for either of these two processes could be obtained. The study provides further evidence against habituation as underlying mechanism for the AEP decrement after stimulus repetition. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 05/2015; DOI:10.1016/j.clinph.2015.04.071 · 2.98 Impact Factor
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- "Nicotinic modulation of the VPC is consistent with previous studies during sustained and selective attention (Giessing et al. 2006; Kumari et al. 2003; Lawrence et al. 2002; Thiel and Fink 2008; Thiel et al. 2005). In agreement with a " bottom–up " role for nicotine, the drug's pro-cognitive effects have been suggested to be in part due to its stimulus filtering properties (Adler et al. 1992; Friedman et al. 1974; Kassel 1997; Knott et al. 2009; Metherate et al. 2012). "
ABSTRACT: Although the attention-enhancing effects of nicotine have been behaviorally and neurophysiologically well-documented, its localized functional effects during selective attention are poorly understood. In this study, we examined the neuronal effects of nicotine during auditory selective attention in healthy human nonsmokers. We hypothesized to observe significant effects of nicotine in attention-associated brain areas, driven by nicotine-induced increases in activity as a function of increasing task demands. A single-blind, prospective, randomized crossover design was used to examine neuronal response associated with a go/no-go task after 7 mg nicotine or placebo patch administration in 20 individuals who underwent functional magnetic resonance imaging at 3T. The task design included two levels of difficulty (ordered vs. random stimuli) and two levels of auditory distraction (silence vs. noise). Significant treatment × difficulty × distraction interaction effects on neuronal response were observed in the hippocampus, ventral parietal cortex, and anterior cingulate. In contrast to our hypothesis, U and inverted U-shaped dependencies were observed between the effects of nicotine on response and task demands, depending on the brain area. These results suggest that nicotine may differentially affect neuronal response depending on task conditions. These results have important theoretical implications for understanding how cholinergic tone may influence the neurobiology of selective attention.Psychopharmacology 12/2014; 232(11). DOI:10.1007/s00213-014-3832-7 · 3.99 Impact Factor
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- "The approaches range from inferring the sources based on the neurotransmitters or circuits that seem to be involved (Adler et al., 1998; Carlsson and Carlsson, 1990) to EEG source localization, both from the scalp (Knott et al., 2009; Oranje et al., 2006) and intracranial (e.g., Boutros et al., 2005; Grunwald et al., 2003), MEG source localization (e.g., Reite et al., 1988; Thoma et al., 2003), and functional magnetic resonance imaging (fMRI; Mathiak et al., 2011; Mayer et al., 2009, 2012; Tregellas et al., 2007). Over time, several brain areas have been suggested to be involved in P50 suppression: e.g., the hippocampus (Adler et al., 1992, 1998; Boutros et al., 2005; Grunwald et al., 2003), thalamus (Carlsson, 1988; Carlsson and Carlsson, 1990), superior temporal gyrus (STG; Knott et al., 2009; Korzyukov et al., 2007; Oranje et al., 2006; Reite et al., 1988; Thoma et al., 2003), both the medial frontal (Jensen et al., 2008; Korzyukov et al., 2007; Oranje et al., 2006; Weisser et al., 2001) and dorsolateral prefrontal cortex (DLPFC; Grunwald et al., 2003; Knight et al., 1989), and the insula (Knott et al., 2009; Mayer et al., 2009) In a study combining these findings Williams et al. (2011) used the STG, the hippocampus, DLPFC, and the thalamus as seed regions in a P50 source localization study. They found a correlation between the hippocampus dipole moment ratio and P50 gating in healthy controls. "
ABSTRACT: Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.Human Brain Mapping 08/2014; 35(8). DOI:10.1002/hbm.22422 · 6.92 Impact Factor