Linkage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor gene polymorphisms: implications for human brain dynamics and cognition.

Event-related oscillations (ERO) offer an alternative theoretical and methodological approach to the analysis of event-related EEG responses. The P300 event-related potential (ERP) is elicited through the superposition of the delta (1-3 Hz) and theta (3-7 Hz) band oscillatory responses. The cholinergic neurotransmitter system has a key function in modulating excitatory post-synaptic potentials caused by glutamate, and therefore influences P300 generation and the underlying oscillatory responses. Here we report significant linkage and linkage disequilibrium between target case frontal theta band, visual evoked brain oscillations and a single nucleotide polymorphism (SNP) from the cholinergic muscarinic receptor gene (CHRM2) on chromosome 7. We also demonstrate significant linkage disequilibrium between CHRM2 SNPs and target case parietal delta band visual evoked oscillations (LD P<0.001). These findings were not observed for the equivalent non-target case data, suggesting a role for the CHRM2 gene in higher cognitive processing in humans.

[1]  D I Boomsma,et al.  Genetic Correlation Between the P300 Event-Related Brain Potential and the EEG Power Spectrum , 2001, Behavior genetics.

[2]  M Schürmann,et al.  Gamma responses in the EEG: elementary signals with multiple functional correlates. , 1997, Neuroreport.

[3]  E. John,et al.  Evoked-Potential Correlates of Stimulus Uncertainty , 1965, Science.

[4]  M. McGue,et al.  Role of the cholinergic muscarinic 2 receptor (CHRM2) gene in cognition , 2003, Molecular Psychiatry.

[5]  Dennis Gabor,et al.  Theory of communication , 1946 .

[6]  M Doppelmayr,et al.  Theta synchronization in the human EEG and episodic retrieval , 1998, Neuroscience Letters.

[7]  T J Sejnowski,et al.  Computational model of carbachol‐induced delta, theta, and gamma oscillations in the hippocampus , 2001, Hippocampus.

[8]  H. Möller,et al.  P300 subcomponents reflect different aspects of psychopathology in schizophrenia , 1999, Biological Psychiatry.

[9]  J. Rohrbaugh,et al.  Visual P300: an interlaboratory consistency study. , 1994, Alcohol.

[10]  E. Donchin.  Event-related Brain Potentials: A Tool in the Study of Human Information Processing , 1979 .

[11]  E. Donchin,et al.  Is the P300 component a manifestation of context updating? , 1988, Behavioral and Brain Sciences.

[12]  R. W. Guillery,et al.  New views of the thalamic reticular nucleus in the adult and the developing brain , 1993, Trends in Neurosciences.

[13]  E. Basar,et al.  Gamma, alpha, delta, and theta oscillations govern cognitive processes. , 2001, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[14]  G. Baal,et al.  Twin and family studies of the human electroencephalogram: a review and a meta-analysis , 2002, Biological Psychology.

[15]  P. Calabresi,et al.  Blockade of M2‐like muscarinic receptors enhances long‐term potentiation at corticostriatal synapses , 1998 .

[16]  E. Halgren,et al.  Effects of muscarinic and adrenergic agonism on auditory P300 in the macaque , 2000, Physiology & Behavior.

[17]  Alcino J. Silva,et al.  Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice , 2003, Nature Neuroscience.

[18]  Erol Başar,et al.  The genesis of human event-related responses explained through the theory of oscillatory neural assemblies , 2000, Neuroscience Letters.

[19]  E. Basar,et al.  Brain oscillations in perception and memory. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[20]  M K McGue,et al.  P300 event-related potential heritability in monozygotic and dizygotic twins. , 1997, Psychophysiology.

[21]  K. Davis,et al.  Interaction of choline and scopolamine in human memory. , 1985, Life sciences.

[22]  J. Rohrbaugh,et al.  Beta power in the EEG of alcoholics , 2002, Biological Psychiatry.

[23]  L. Bierut,et al.  Familial transmission of substance dependence: alcohol, marijuana, cocaine, and habitual smoking: a report from the Collaborative Study on the Genetics of Alcoholism. , 1998, Archives of general psychiatry.

[24]  J. Yordanova,et al.  Event‐related alpha oscillations are functionally associated with P300 during information processing , 1998, Neuroreport.

[25]  John Rohrbaugh,et al.  Resting EEG in offspring of male alcoholics: beta frequencies. , 2004, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[26]  D. Comings,et al.  Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women. , 2002, American journal of medical genetics.

[27]  E. Basar,et al.  Detection of P300 Waves in Single Trials by the Wavelet Transform (WT) , 1999, Brain and Language.

[28]  Enoch Callaway,et al.  The Pharmacology of Human Information Processing , 1983 .

[29]  A. Papanicolaou,et al.  Magnetoencephalography reveals two distinct sources associated with late positive evoked potentials during visual oddball task. , 1993, Cerebral cortex.

[30]  K. Meador,et al.  Central cholinergic systems and the P3 evoked potential. , 1987, The International journal of neuroscience.

[31]  E. Basar,et al.  Are cognitive processes manifested in event-related gamma, alpha, theta and delta oscillations in the EEG? , 1999, Neuroscience Letters.

[32]  C. Amos.  Robust variance-components approach for assessing genetic linkage in pedigrees. , 1994, American journal of human genetics.

[33]  Petr Marsalek,et al.  Event-related potentials--the P3 wave. , 2003, Acta neurobiologiae experimentalis.

[34]  J. Polich,et al.  Cognitive and biological determinants of P300: an integrative review , 1995, Biological Psychology.

[35]  J Blangero,et al.  Quantitative trait loci analysis of human event-related brain potentials: P3 voltage. , 1998, Electroencephalography and clinical neurophysiology.

[36]  R. Lewontin.  The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. , 1964, Genetics.

[37]  Tatiana Foroud,et al.  Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Dr. Robert Miller.  Cortico-Hippocampal Interplay and the Representation of Contexts in the Brain , 1991, Studies of Brain Function.

[39]  L. Butcher,et al.  'Cat P300' disappears after septal lesions. , 1988, Electroencephalography and clinical neurophysiology.

[40]  J. Lachaux,et al.  A simple measure of correlation across time, frequency and space between continuous brain signals , 2003, Journal of Neuroscience Methods.

[41]  L. Almasy,et al.  Multipoint quantitative-trait linkage analysis in general pedigrees. , 1998, American journal of human genetics.

[42]  M Doppelmayr,et al.  Brain oscillations and human memory: EEG correlates in the upper alpha and theta band , 1997, Neuroscience Letters.

[43]  T. Sejnowski,et al.  Cholinergic induction of oscillations in the hippocampal slice in the slow (0.5–2 Hz), theta (5–12 Hz), and gamma (35–70 Hz) bands , 2000, Hippocampus.

[44]  M. MacIver,et al.  Physiology, pharmacology, and topography of cholinergic neocortical oscillations in vitro. , 1997, Journal of neurophysiology.

[45]  T. Sejnowski,et al.  Dynamic Brain Sources of Visual Evoked Responses , 2002, Science.

[46]  Vasil Kolev,et al.  A new metric for analyzing single-trial event-related potentials (ERPs): application to human visual P300 delta response , 1995, Neuroscience Letters.

[47]  R. Knight,et al.  Mechanisms of human attention: event-related potentials and oscillations , 2001, Neuroscience & Biobehavioral Reviews.

[48]  E. Ba§ar,et al.  EEG-Brain dynamics: Relation between EEG and brain evoked potentials , 1982 .

[49]  D. Potter,et al.  Scopolamine impairs memory performance and reduces frontal but not parietal visual P3 amplitude , 2000, Biological Psychology.

[50]  G. Mangun,et al.  ERP and fMRI measures of visual spatial selective attention , 1998, Human brain mapping.

[51]  E. Basar,et al.  Does frequency analysis lead to better understanding of human event related potentials. , 1985, The International journal of neuroscience.

[52]  J. Rohrbaugh,et al.  Endogenous potentials generated in the human hippocampal formation and amygdala by infrequent events. , 1980, Science.

[53]  T. Demiralp,et al.  A model for P300 generation based on responses to near-threshold visual stimuli. , 1999, Brain research. Cognitive brain research.

[54]  D. Ruchkin,et al.  Working memory and preparation elicit different patterns of slow wave event-related brain potentials. , 1995, Psychophysiology.

[55]  W. Roth,et al.  Auditory event-related potentials in schizophrenia and depression , 1981, Psychiatry Research.

[56]  K. Meador,et al.  Cholinergic modulation of human P3 event‐related potentials , 1987, Neurology.

[57]  W. Klimesch,et al.  Theta synchronization during episodic retrieval: neural correlates of conscious awareness. , 2001, Brain research. Cognitive brain research.

[58]  E Başar,et al.  A new strategy involving multiple cognitive paradigms demonstrates that ERP components are determined by the superposition of oscillatory responses , 2000, Clinical Neurophysiology.

[59]  S. Morzorati,et al.  Heritable features of the auditory oddball event-related potential: peaks, latencies, morphology and topography. , 1994, Electroencephalography and clinical neurophysiology.

[60]  M Schürmann,et al.  Delta responses and cognitive processing: single-trial evaluations of human visual P300. , 2001, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[61]  E. Boerwinkle,et al.  The use of measured genotype information in the analysis of quantitative phenotypes in man , 1986, Annals of human genetics.

[62]  E. Perry,et al.  Acetylcholine in mind: a neurotransmitter correlate of consciousness? , 1999, Trends in Neurosciences.

[63]  L. Almasy,et al.  Linkage analysis demonstrates that the prothrombin G20210A mutation jointly influences plasma prothrombin levels and risk of thrombosis. , 2000, Blood.

[64]  L. Almasy,et al.  Variance component methods for detecting complex trait loci. , 2001, Advances in genetics.

[65]  A. Antal,et al.  Visual discrimination and P300 are affected in parallel by cholinergic agents in the behaving monkey , 1994, Physiology & Behavior.

[66]  G. Geffen,et al.  Effects of Memory Load and Distraction on Performance and Event-Related Slow Potentials in a Visuospatial Working Memory Task , 1997, Journal of Cognitive Neuroscience.

[67]  D. Boomsma,et al.  Individual differences in P300 amplitude: a genetic study in adolescent twins , 1998, Biological Psychology.

[68]  Lalu Mansinha,et al.  Localization of the complex spectrum: the S transform , 1996, IEEE Trans. Signal Process..

[69]  L. Kaufman,et al.  The hippocampal formation as a source of the slow endogenous potentials. , 1983, Electroencephalography and clinical neurophysiology.

[70]  L. Almasy,et al.  Exploring Positional Candidate Genes: Linkage Conditional on Measured Genotype , 2004, Behavior genetics.

[71]  Ulrich Hegerl,et al.  Neurochemical Substrates and Neuroanatomical Generators of the Event-Related P300 , 1999, Neuropsychobiology.

[72]  Tatiana Foroud,et al.  Linkage mapping of beta 2 EEG waves via non‐parametric regression , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[73]  J. Rohrbaugh,et al.  Heritability of event-related brain potentials in families with a history of alcoholism. , 1999, American journal of medical genetics.