Event-related oscillations in the parietal cortex of adult alcohol-preferring (P) and alcohol-nonpreferring rats (NP)
Introduction
Genetic selection studies have resulted in a number of high-drinking lines of mice and rats (see Bell et al., 2006, Green and Grahame, 2008). The alcohol-preferring (P) and -nonpreferring (NP) rat lines are one of the most extensively examined animal models of alcoholism (Li et al., 1993). These rats were developed for differences in home cage ethanol consumption to study ethanol-drinking behaviors and their consequences (Bell et al., 2006, Lumeng et al., 1977). Selectively bred P rats have been shown to voluntarily consume levels of 10% ethanol of more than 5 g/kg/d, with an ethanol preference ratio (vs. water) of greater than 2:1. The NP rats generally consume levels of 10% ethanol of less than 1.5 g/kg/d, with an ethanol preference ration of less than 0.2:1. These lines have been the focus of intensive study of the behavioral, neurobiological, and neurophysiologic factors that contribute to ethanol consumption (for reviews, see Bell et al., 2006, Li et al., 1993, McBride and Li, 1998).
Electrophysiologic differences between the rat lines have also been demonstrated (Breen and Morzorati, 1996, Ehlers et al., 1991, Ehlers et al., 1992, Ehlers et al., 1999, Morzorati et al., 1994, Robledo et al., 1993, Robledo et al., 1994). The study of neurophysiologic endophenotypes in P and NP rats with well-differentiated ethanol-related phenotypes could be an additional tool for identifying susceptibility genes for ethanol dependence. We have previously characterized the electrophysiologic profile of P and NP rats and found that P rats have significantly lower amplitude of the P3 component of the event-related potential (ERP), when compared with NP rats (Ehlers et al., 1999). This finding is similar to what has been reported for human subjects at differing risk for ethanol dependence (for review, see Porjesz et al., 2005).
There is evidence to suggest that ERPs may originate from an additive evoked activation of neural assemblies independent of ongoing electroencephalogram (EEG) as well as by the phase resetting of ongoing EEG oscillations in response to sensory input (for review, see Rangaswamy and Porjesz, 2008, Sauseng et al., 2007). Considerable efforts have been made in understanding how these models may potentially explain the generation of human ERPs. For instance, it has been proposed that the P3 component arises from a series of superimposed event-related oscillations (EROs) that are induced by sensory or cognitive processes that influence the dynamics of EEG rhythms (e.g., Demiralp et al., 2001, Karakas et al., 2000, Yordanova and Kolev, 1996). EROs are estimated by performing a decomposition of the EEG signal into phase and magnitude information over a range of frequencies and then the changes in those frequencies are characterized over a millisecond time scale with respect to task events. EROs have been demonstrated to be sensitive measures of both normal and abnormal cognitive functioning in humans (see Basar et al., 1999, Basar et al., 2001, Gevins et al., 1998, Klimesch et al., 1997, Schurmann et al., 2001). Additionally, these oscillations have been linked to several relevant genes associated with ethanol dependence phenotypes (Begleiter and Porjesz, 2006, Edenberg et al., 2004, Jones et al., 2004).
Studies have further demonstrated that delta and theta EROs are the primary contributors to the human P3 ERP component (Basar et al., 1999, Basar-Eroglu et al., 1992, Demiralp et al., 2001, Karakas et al., 2000, Schurmann et al., 2001). Reductions in P3 amplitude have been related to decreased cortical ERO energy and also to higher phase variability and weaker phase locking. For instance, it has been shown that the reduction of P3 amplitude during retrieval of a working memory task is associated with a decrease in delta ERO power and an increase in phase variability (Schack and Klimesch, 2002). In addition to their role in generating the P3 ERP component, evoked oscillations have also been shown to play a role in the generation of other ERP components, including the P1–N1 complex. There is evidence to suggest that alpha and theta evoked power and phase locking (PL) plays an important role in the generation of the P1–N1 complex (Klimesch et al., 2004). However, whether differences in ERO energy and phase variability play a role in the different neurophysiologic profiles identified in animal models has been less studied.
In view of the evidence from human studies of the link between alcohol dependence and ERO energy (Porjesz et al., 2005), characterizing the relationship between an ethanol preference phenotype and changes in EROs, translating this information to an animal model may provide valuable information on the mechanisms underlying these measures. The present study extended our initial analyses of neurophysiologic endophenotypes in P and NP rats to EROs generated in cortical sites in response to an auditory oddball paradigm (standard, rare, and noise tones). In this study, we investigated oscillatory activity in the delta, theta, and alpha/beta frequency ranges in the parietal cortex of P and NP rats within the temporal window of the P3 ERP response. ERO and PL analyses were accomplished from the same datasets that were used to generate the ERP data reported in a previous publication (Ehlers et al., 1999). We hypothesize that differences in hippocampal P3 amplitudes previously reported in P and NP rats (Ehlers et al., 1999) are associated to differences in delta and theta ERO oscillatory activity.
Section snippets
Animals
Twenty-five rats, 14 P and 11 NP male rats, of the 42nd generation, bred at Indiana University were received at The Scripps Research Institute weighing 281–410 g. All rats had ad libitum access to food and water. A detailed description of the environmental conditions of rats can be found elsewhere (Ehlers et al., 1999). The work described herein adheres to the guidelines stipulated in the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals (NIH publication No.
Effect of tone type on ERO energy and PLI
Two-way repeated measures ANOVA with ERO energy as dependent variable revealed a significant main effect of tone in the theta and alpha/beta frequency bands in the parietal cortex (Table 1). Post hoc pairwise comparisons showed lower ERO energy in the parietal theta and alpha/beta bands occurred in response to rare and noise tones, compared with standard tones (Table 1).
Two-way repeated measures ANOVA with PLI as dependent variable revealed a significant main effect of tone in the delta, theta,
Discussion
Brain oscillations have been proposed to represent neurophysiologic correlates of human information processing and cognitive function (Basar et al., 1999, Karakas et al., 2000). They have also been considered endophenotypes for complex genetic disorders, including drug addiction and psychiatric disorders (for reviews, see Begleiter and Porjesz, 2006, Porjesz et al., 2005). There is evidence to suggest that individuals with a positive family history of alcoholism have decreased P3 amplitude
Acknowledgments
Supported in part by National Institute on Alcoholism and Alcohol Abuse grant AA006059 and AA014339 and by the Stein Endowment fund. The computer programs were written by Dr James Havstad. The authors thank Derek Wills, Evelyn Phillips, Phil Lau, and Jennifer Roth for assistance in analyses and Shirley Sanchez for assistance in editing.
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2016, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :It thus appears reasonable to conclude that if the power in a spontaneous oscillatory frequency is high, there is a relatively higher probability that partial phase resetting of the frequency would render higher power to the phase-locked oscillatory frequency compared to a spontaneous oscillatory frequency that had lower power. However, there is evidence that points to lower phase locking rates among impulsive university students (Knyazev et al., 2008), schizophrenia patients (Basar-Eroglu et al., 2009), and alcohol preferring rats (Criado and Ehlers, 2010). Further, the diffused brain dysfunction hypothesis that postulates that alcohol causes generalized deficits that involve many structures of the brain, is associated with an abnormal EEG profile, and dysfunction resembles that of premature aging (Glenn et al., 1994; Kamarajan et al., 2004; Newman, 1978; Parsons, 1994; Tivis et al., 1995) may also lend additional support to the present observation showing lower evoked power during task demands.
Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the nucleus basalis magnocellularis
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2014, International Journal of PsychophysiologyCitation Excerpt :Importantly, a converging line of evidence suggests that reduced P3 indicates a genetically transmitted deficit predating alcohol use and abuse, rather than a consequence of heavy drinking: the reduction of P3 is present in high-risk (i.e. family history positive) adolescents was present before the onset of drinking (Hill and Shen, 2002; Hill et al., 1999; Hill et al., 2000); P3 is not significantly affected by alcohol use (Perlman et al., 2009); in longitudinal studies reduced P3 prospectively predicted the onset of alcohol abuse (Gilmore et al., 2012) as well as aggression and crime (Gao and Raine, 2009); in non-alcohol dependent social drinkers without family history of alcoholism P3 amplitude was unrelated to lifetime alcohol intake (Bijl et al., 2005); finally, a co-twin control study (Carlson et al., 2002) has shown that in twin pairs discordant for AUDs the alcohol abusing/dependent twins' amplitude did not differ from that of non-alcoholic co-twins, providing further evidence that P3 amplitude reduction is a genetically transmitted marker of risk, rather than consequence of drinking. Interestingly, animal models show a pattern of ERP differences that parallels the human findings described above: selectively bred alcohol-preferring rats show reduced P3 amplitude in the parietal cortex and increased fast-frequency EEG activity compared with and non-preferring rats (Criado and Ehlers, 2010). Thus, high heritability of P3 (and associated event-related theta oscillations) in the general population, its robust familial association with alcoholism, genetic correlations with a broader externalizing trait, and little modification by alcohol use, makes it a good intermediate phenotype (endophenotype) for genetically transmitted vulnerability to alcoholism.
Cholinergic modulation of event-related oscillations (ERO)
2014, Brain ResearchCitation Excerpt :EROs are typically estimated by a decomposition of the EEG signal into phase and magnitude information for a range of frequencies and then changes in those frequencies are characterized with respect to their energy (amplitude) and phase relationships over a millisecond time scale with respect to task events (Ehlers et al., 1994). EROs have been demonstrated to be sensitive measures of both normal (Basar et al., 1999; Gevins, 1998) and abnormal cognitive functioning (Begleiter and Porjesz, 2006; Criado and Ehlers, 2009, 2010b; Ehlers et al., 2012; Porjesz and Begleiter, 2003). The purpose of the present study was to examine whether selective cholinergic lesions of the medial septum area (MS) or the nucleus basalis magnocellularis (NBM) influence the amplitude and phase characteristics of ERO oscillatory activity in the delta, theta, alpha, beta and gamma frequency bands in the frontal cortex, DHPC and central amygdala elicited passively with an acoustic oddball paradigm in adult rats.