The effects of smoking cigarettes on sensory gating, P50 and stimulus-bound gamma band (32-48 Hz) oscillations were examined in two paradigms: paired-tone and oddball. During a paired-tone paradigm, our previous work (Crawford, McClain-Furmanski, Castagnoli, & Castagnoli, Neuroscience Letters 317(2002) 151-155) found heavy smokers exhibited chronic (rather than acute) effects in the frontal region: (1) larger P50 and GBO responses; (2) greater P50 and GBO sensory gating suppression, as well as earlier GBO sensory gating suppression. During an oddball paradigm, we (McClain-Furmanski, Crawford, Castagnoli & Castagnoli, in prep.) found an acute effect between 0 and 20 ms post-stimulus in the GBO, however we were unable to determine whether this effect was due to nicotine or the act of smoking. In the present study, participants were 24 heavy cigarette (20+/day) right-handed, non-depressed smokers with no known medical or psychiatric problems, and no known familial history of psychiatric problems. In the morning, they were tested after abstaining overnight and after smoking a cigarette containing either 1.1 mg of nicotine, or a denicotinized cigarette (< 0.04 mg). In study 1 (oddball paradigm), although some effects were found related to nicotine and/or smoking, observed as condition by group interactions with the groups changing differently across conditions, they differed in temporal and spatial localization from those hypothesized. Thus, the present study was unable to differentiate between nicotine effects and effects due to the act of smoking. In study 2 (paired-pulse paradigm), in traditional evoked potential analysis, we observed signficant chronic sensory gating, as measured by the ratio of N40-P50 amplitude in response to the second tone (S2) as compared to the response to the first tone (S1). The effect was greatest at the hypothesized location (FCZ). In time series analysis of the underlying GBO, we replicated our earlier findings in that S2/S1 effects could be detected across 60 msec of the response. These results are discussed in relation to the neurochemistry and neural processes underlying sensory gating at GBO production, as well as in relation to the known and hypothesized psychpharmacological effects of smoking tobacco. Furthermore, these results are related to the theorized basis of addiction. / Ph. D.

Sensory gating helps prevent incoming irrelevant sensory information from entering into the higher cortex and ensures normal information processing. Sensory gating is seen as the ability of the nervous system to modulate its sensitivity to incoming stimuli (Braff & Geyer, 1990; Adler, Olincy, Waldo, Harris & Griffith, et al., 1998). Smoking tobacco can facilitate early sensory gating in schizophrenics, and enhance prepulse inhibition asymmetry (right greater than left) in individuals with schizotypal personality. The purpose of this study was to test the following hypotheses: 1) Individuals with schizotypal personalities have poorer sensory gating than those without them. 2) Among individuals with schizotypy (high schizotypy), those who smoke have better sensory gating than those who do not smoke; among those without schizotypy (low schizotypy), smokers will demonstrate better sensory gating. 3) After abstaining, schizotypal smokers will show increased sensory gating due to smoking. 4) Individuals with schizotypy will show greater P50 deficits in the left hemisphere, and smoking can enhance this asymmetry (left greater than right). From 613 online-surveyed participants, 39 (18 men) right-handed undergraduates (Mean age = 18.87) were selected to represent four groups: High and Low Schizotypy, half of which were smokers, and half were non-smokers. Smokers were tested while abstaining and after smoking. Non-smokers were tested twice in the same manner without smoking. P50 sensory gating, P50 amplitude and P50 latency were analyzed separately at frontal (F3, F4, Fz), fronto-central (FC3, FC4, FCz), central (C3, C4, Cz), centro-parietal (CP3, CP4, Cpz) and parietal (P3, P4, Pz) regions. With respect to the hypotheses of the study, it was found that: 1) Sensory gating, as assessed by S2 (P50-N40)/S1 (P50-N40), was greater at frontal-central and central regions in comparison to mid-frontal and parietal regions. 2) Furthermore, sensory gating was significantly greater at midline than left or right hemispheres. 3) Condition 1 showed better sensory gating than Condition 2. 4) The High Schizotypy group showed poorer sensory gating than the Low Schizotypy group among non-smokers. 5) Smokers showed poorer sensory gating than non-smokers in the Low Schizotypy group. In terms of P50 amplitude, it was found that: 1) FCz and Cz showed the highest P50 amplitude, greater than all other sites. 2) S1 had higher P50 amplitude than S2. 3) The low schizotypy individuals had significantly greater P50 amplitude in the left than in the right fronto-central region, but the high schizotypy individuals showed more P50 amplitude in the right hemisphere than did the low schizotypy individuals. 4) Smokers showed a greater left than right P50 amplitude in centro-parietal region, whereas the non-smokers showed the opposite asymmetry with a greater right than left P50 amplitude in central, centro-parietal and parietal regions. In terms of P50 latency, it was found that: 1) The P50 latency became significantly slower from posterior to anterior sites. 2) In HiS/S and LoS/NS groups, Condition1 was faster than Condition 2. In LoS/S and HiS/NS groups, Condition1 was slower than Condition 2. 3) Among smokers, left hemisphere latency was shorter than right hemisphere for S1, but for S2, left hemisphere was slower than right hemisphere. Among non-smokers, left and right hemisphere latencies were almost the same for S1 and S2. / Master of Science

Ten to 15% of the population is temperamentally shy and have elevated physiological stress responses to novel social situations. Yet, the neural mechanisms underlying this personality trait are not fully understood (Beaton et al., 2009; Schmidt et al., 1997). Efficiently attending to, acting on, and remembering relevant stimuli and filtering out less important information is critical given the sheer volume of sensory and perceptual stimuli the brain is exposed to. Relevant stimuli that garner attention are remembered and consolidated with existing memories. Stimuli that do not warrant extended attention are ignored or habituated to in a process underpinned by cortical and subcortical inhibitory brain networks that reduce processing load on finite attentional resources (Freedman et al., 1991; Adler et al., 1998). Inefficient filtering of irrelevant stimuli could underpin anxiety in those with temperamental shyness and anxiety (Aron, Aron, & Davies, 2005). We measured the P50 auditory event-related potential (ERP) using a paired auditory click paradigm, as well as self-reported social anxiety and shyness, and salivary cortisol in two groups of healthy young adults selected for being very shy or very gregarious. While shy and gregarious groups demonstrated a similar P50 ERP to sound one (S1), the shy group showed elevated P50 amplitudes in response to the second sound (S2) compared to the gregarious group. Participants categorized as being lower or higher on social anxiety displayed a reverse pattern: those higher in social anxiety had a reduced response to S1 compared to those lower in social anxiety, yet a similar response to S2. Further, higher salivary cortisol predicted smaller differences and larger ratios in the P50 ERP from S1 to S2.

abstract: Sensory gating is a process by which the nervous system preferentially admits stimuli that are important for the organism while filtering out those that may be meaningless. An optimal sensory gate cannot be static or inflexible, but rather plastic and informed by past experiences. Learning enables sensory gates to recognize stimuli that are emotionally salient and potentially predictive of positive or negative outcomes essential to survival. Olfaction is the only sensory modality in mammals where sensory inputs bypass conventional thalamic gating before entering higher emotional or cognitive brain regions. Thus, olfactory bulb circuits may have a heavier burden of sensory gating compared to other primary sensory circuits. How do the primary synapses in an olfactory system "learn"' in order to optimally gate or filter sensory stimuli? I hypothesize that centrifugal neuromodulator serotonin serves as a signaling mechanism by which primary olfactory circuits can experience learning informed sensory gating. To test my hypothesis, I conditioned genetically-modified mice using reward or fear olfactory-cued learning paradigms and used pharmacological, electrophysiological, immunohistochemical, and optical imaging approaches to assay changes in serotonin signaling or functional changes in primary olfactory circuits. My results indicate serotonin is a key mediator in the acquisition of olfactory fear memories through the activation of its type 2A receptors in the olfactory bulb. Functionally within the first synaptic relay of olfactory glomeruli, serotonin type 2A receptor activation decreases excitatory glutamatergic drive of olfactory sensory neurons through both presynaptic and postsynaptic mechanisms. I propose that serotonergic signaling decreases excitatory drive, thereby disconnecting olfactory sensory neurons from odor responses once information is learned and its behavioral significance is consolidated. I found that learning induced chronic changes in the density of serotonin fibers and receptors, which persisted in glomeruli encoding the conditioning odor. Such persistent changes could represent a sensory gate stabilized by memory. I hypothesize this ensures that the glomerulus encoding meaningful odors are much more sensitive to future serotonin signaling as such arousal cues arrive from centrifugal pathways originating in the dorsal raphe nucleus. The results advocate that a simple associative memory trace can be formed at primary sensory synapses to facilitate optimal sensory gating in mammalian olfaction. / Dissertation/Thesis / Ph.D. Biology 2012

No description available.

Pain is a complex, ubiquitous phenomenon that can be debilitating and costly. Although it is well known that some individuals can easily tolerate pain while others are more intolerant to pain, little is known of the neurophysiological bases of these differences. Because differences in sensory information processing may underlie variability in tolerance to pain and because measures of sensory gating are used to explore differences in sensory information processing, sensory gating among college students (N = 14) who are tolerant or intolerant to pain was investigated. This investigation explored the hypothesis that those who were more tolerant to pain would evidence greater sensory gating. Pain tolerance was first determined using a cold pressor task. Sensory gating was then determined by the amount of attenuation of the amplitude of a second painful, electrical, somatosensory stimulus (S2) in relation to the amplitude of an identical first stimulus (S1) in a paired-stimulus evoked potential (EP ) paradigm. The results obtained showed the intolerant group exhibiting greater physiological reactivity than the tolerant group, indicating that the tolerant group attained greater sensory gating than the intolerant group. / Ph. D.

Smoking is one of the leading causes of death in the world. About 80% of smokers start smoking before the age of 18. In the Appalachian area and the South in the United States, smoking percentages among adults and adolescents are higher than in other regions. Female smoking shows a variety of different trends from male smoking, and smoking brings particular health problems related to production to female smokers. These findings highlighted the importance of studying female teenage smokers in southwest Virginia. The initial project aimed to identify risk factors that might prevent smoking in an early stage. Dr. Helen Crawford led the Cognitive Neuroscience Lab at Virginia Tech in discovering the psychophysiological vulnerabilities of female teenage smokers. Toward this end, event-related potential (ERP), personality, and behavioral data were collected in teenage female smokers and non-smokers. These data were analyzed to examine possible psychophysiological vulnerabilities in female teenage smokers such as deficits in brain and cognitive function, personality traits, and environment influences. The purpose of this dissertation is to further analyze these data to elaborate and clarify the relationships among these vulnerabilities toward understanding teenage smoking behavior. Participants were 49 teenage girls (smokers and non-smokers) with age from 14 to 18. The measures included sensory gating, platelet MAO-B activity, attention, memory, temperament, schizotypal personality, recognition of facial expressions, taste and smell. The initial set of analyses compared smokers and non-smokers, including those classified as high and low dependent, on all dependent measures. The results suggested some psychophysiological vulnerabilities in female teenage smokers, which have been used as support for the self-medication and the orbito-frontal dysfunction models of why teenagers smoke (Crawford et al., 2004). Further examination of these factors may help teenagers to reduce the smoking dependency and possibly improve cognitive function. Specifically, this dissertation focused on the role of the variable of monoamine oxidase-B (MAO-B) in the correlations among sensory gating, MAO and other cognitive and personality measures. All smokers were divided into high and low MAO groups first. Comparison analyses were conducted between them. The high MAO group showed better sensory gating function than the low MAO group. Correlation analyses were conducted among all of the measures. The significant linear relationships between MAO and sensory gating, MAO and CO level and MAO and temperament were demonstrated. MAO activity positively correlated with the sensory gating function and negatively correlated with CO level and temperament characteristics. Finally, to explore the mechanisms of the relationship between MAO and sensory gating, the neurotransmitter systems related to MAO and sensory gating were discussed. / Ph. D.

No description available.

La schizophrénie est une pathologie caractérisée par des symptômes positifs (idées délirantes et hallucinations), des symptômes négatifs (émoussement affectif, alogie, apragmatisme, retrait social) et des symptômes de désorganisation (cognitifs et affectifs). Cette pathologie est également associée à des altérations cognitives, perceptuelles et de la qualité de vie. La physiopathologie de la schizophrénie reste mal connue. Récemment, des travaux ont mis en avant le rôle central des processus inflammatoires chroniques dans la physiopathologie de ce trouble psychiatrique. En particulier, il a été montré que la CRP (Protéine C-Réactive), marqueur inflammatoire chronique aspécifique et facile à doser dans une prise de sang, est augmentée dans la schizophrénie. La CRP est reliée à la symptomatologie clinique et aux altérations cognitives des patients souffrant de schizophrénie. Mais le lien entre altérations perceptuelles et de la qualité de vie et CRP reste à explorer. / Schizophrenia is an illness characterized by positive symptoms (delusions and hallucinations), negative symptoms (reduced emotional expression, alogia, apragmatism, reduced social engagement) and disorganized symptoms (cognitive and affective). This pathology is also associated to cognitive and perceptual alterations and to quality of life alterations. The physiopathology of schizophrenia is still unclear. Recently, papers put forward the central role of chronic inflammatory process in pathophysiology of this psychiatric disorder. In particular, CRP (C-Reactive Protein), a nonspecific marker of chronic inflammation and easy to measure with blood sample, was shown to be increased in schizophrenia. CRP is connected to clinical symptomatology and to cognitive alterations in patients with schizophrenia. However the connection between alterations of perception, quality of life and CRP remains to be explored.

L’objectif de cette thèse a été de développer des outils d’exploration des modifications perceptuelles lors de l’écoute de sons complexes dans la schizophrénie et de confronter les résultats de ces outils à des données neurophysiologiques. Le premier résultat de notre thèse est d’avoir confirmé dans la modalité auditive des modifications de l’organisation perceptuelle lors de l’écoute de sons complexes. En effet, nous avons montré, chez les patients souffrant de schizophrénie comparativement aux témoins, d’une part une difficulté de catégorisation des sons environnementaux de type son d’impact, et d’autre part, une modification de la perception de la familiarité et de la bizarrerie pour des sons environnementaux et abstraits, indiquant une modification d’organisation des données de l’audition dans une forme univoque et consensuelle.Le deuxième résultat de notre thèse est d’avoir confirmé, par une méthode d’induction perceptuelle consistant à présenter des stimuli plus ou moins envahissants, la présence d’un sentiment d’envahissement perceptuel plus important chez les patients souffrants de schizophrénie comparativement aux témoins. Cet envahissement perceptuel était corrélé significativement avec une mesure neurophysiologique du filtrage sensoriel par potentiels évoqués dans le paradigme des doubles clics audio (diminution d’amplitude de la composante P50 au deuxième stimulus comparativement au premier stimulus). Nous avons également traduit et validé en langue française un auto-questionnaire appelé Sensory Gating Inventory (SGI) permettant de compléter l’évaluation psychophysiologique des modifications perceptuelles reliées aux anomalies du filtrage sensoriel. / The aim of this PhD was to develop tools for analyzing perceptual modifications induced by complex sounds in schizophrenia and to relate these changes to neurophysiological data. The first result of our work enabled to confirm that complex sounds modify the auditory perceptual organization. Indeed, we first showed a deficit of categorization of environmental sounds (impact sounds) in patients with schizophrenia compared with controls, and secondly a difference in the perception of familiarity and strangeness for environmental and abstract sounds, indicating a modification of data organization of hearing in a unique and consensual form.The second result of our work revealed, by a perceptual induction method, the presence of a larger perceptual sense of inundation in patients suffering from schizophrenia compared with controls when submitted to more or less invasive stimuli. This perceptual inundation was significantly correlated with a neurophysiological measurement of sensory gating with evoked responses in the paradigm of double audio clicks (decrease in amplitude of the P50 component after the second stimulus as compared to the first stimulus). We have also translated a self-administered questionnaire called “Sensory Gating Inventory” (SGI) to French and validated it in order to complete the psychophysiological assessment of perceptual changes related to abnormal sensory gating.