Development of a functional MRI Olfactory Protocol

Many people can spend a few days with an acute form of sinusitis, a stuffy nose, or sinus congestion that inhibits their ability to smell, but there are fourteen million Americans over the age of fifty that suffer from some form of chronic olfactory dysfunction. Some neurological disorders such as Parkinson\u27s disease and Alzheimer\u27s disease have demonstrated that olfactory dysfunction is a frequent and early sign. While these diseases have no known cure, there are medicines that exist to slow the progression of such debilitating illnesses. By identifying such diseases in their early stages, we can improve the quality of life for millions of people throughout the world. This research project will begin to open the doors for more investigation into the relationship of olfaction and Parkinson\u27s disease, Alzheimer\u27s disease, and even epilepsy by the development of an fMRI olfactory stimulation protocol. This protocol successfully identified the olfactory regions of the brain of normal patients

Optimization of Functional MRI methods for olfactory interventional studies at 3T

Functional MRI technique is vital in investigating the effect of an intervention on cortical activation in normal and patient population. In many such investigations, block stimulation paradigms are still the preferred method of inducing brain activation during functional imaging sessions because of the high BOLD response, ease in implementation and subject compliance especially in patient population. However, effect of an intervention can be validly interpreted only after reproducibility of a detectable BOLD response evoked by the stimulation paradigm is first verified in the absence of the intervention. Detecting a large BOLD response that is also reproducible is a difficult task particularly in olfactory Functional MRI studies due to the factors such as (a) susceptibility-induced signal loss in olfactory related brain areas and (b) desensitization to odors due to prolonged odor stimulation, which is typical when block paradigms are used. Therefore, when block paradigms are used in olfactory interventional Functional MRI studies, the effect of the intervention may not be easily interpretable due to the factors mentioned above. The first task of this thesis was to select a block stimulation paradigm that would produce a large and reproducible BOLD response. It was hypothesized that a BOLD response of this nature could be produced if within-block and across-session desensitization could be minimized and further, that desensitization could be minimized by reducing the amount of odor by pulsing the odor stimulus within a block instead of providing a continuous odor throughout the block duration. Once the best paradigm was selected, the second task of the thesis was to select the best model for use in general linear model (GLM) analysis of the functional data, so that robust activation is detected in olfactory related brain areas. Finally, the third task was to apply the paradigm and model that were selected as the best among the ones tested in this thesis, to an olfactory interventional Functional MRI study investigating the effect of food (bananas) eaten to satiety on the brain activation to the odor related to that food. The methods used in this thesis to ensure valid interpretation of an interventional effect, can serve as a template for the experimental design of future interventional Functional MRI studies

Characterization of mismatch between behavioral stimuli and FRMI data using the Kalman filter

The advance of blood oxygen level dependent function magnetic resonance imaging, (BOLD fMRI), allows researchers to non-invasively investigate the functioning human brain. The BOLD fMRI response to brief stimuli is called the hemodynamic response function (HRF), which can vary across brain regions and across subjects. Models of the HRF are used to increase sensitivity of statistical maps; however, they often don\u27t account for spatial and temporal variance. Physiological effects, such as learning, fatigue or habituation, introduce mismatch between statistical models and the data. Methods that use minimal a priori information and track time varying signals are able to show the processing of information over time and thereby elucidate such effects. The method of Kalman filtering was employed to characterize mismatches occurring between statistical models and BOLD data. The Kalman filter operates on data point by point. This contrasts regression techniques, that use blocks of data to find a single estimate. Functional MRI data was collected from ten subjects at Columbia University while they engaged in three visual experiments and four olfactory experiments. The Kalman filter was used to distinguish between the fMRI response to a 2 second and a 12 second visual stimulus. The results from this analysis showed the extracted responses from the two stimuli significantly differed. The same analysis was also used to distinguish between primary and secondary olfactory cortices. These brain regions have shown differential temporal responses to odorants. The extracted responses were not significantly different. Extracted responses from one stimulus (visual or olfactory) were used to test if this subject specific information would predict the next experimental session, better than standard a priori models of the data. The results of this analysis showed this not to be the case. The extracted response over time to the odorant stimuli were tractable with the Kalman filter, and shown to decay as predicted from the literature. This temporal change was hypothesized to decrease predictability from one session to the next, causing the null result. To alleviate this, models were tested for their predictability across hemisphere, within session. The results showed that inclusion of subject specific information improved this fit over other a priori models. The implications of this analysis are the ability to extract temporally varying fMRI responses over an experiment without knowledge of the expected response to a stimuli. Results of such analyzes offer a look into how the brain responds and processes stimuli over the course of an experiment. This contrasts method that offer summary, or average, results from an experiment

AN FMRI STUDY OF THE IMPACT OF OLFACTORY CUES ON CIGARETTE CRAVING

Cigarette smoking remains the number one preventable cause of death in the United States. Cigarette craving during a quit attempt has been linked to relapse, suggesting it is a clinically significant construct. This study investigated an understudied method of craving reduction, involving the administration of olfactory cues after craving induction. Olfactory cues may work to combat craving because they strongly engage attentional and emotional processing, can induce vivid autobiographical memory (AM) recall, and because olfactory processing brain regions overlap with regions involved in craving. Using both general linear model (GLM) and multivoxel pattern analysis (MVPA) approaches, this study collected fMRI and behavioral data to build upon a set of behavioral studies that have found odors to be an effective craving reduction tool. The neural response during a strong craving state was assessed in 39 adult daily smokers across a variety of craving, olfactory, and AM regions before and after an odor exposure paradigm, during which half of the participants smelled a pleasant odor cue and half smelled a neutral odor. Results indicate that exposure to a pleasant odor cue (compared to a neutral odor cue) changed the neural response in craving related regions. Odor characteristics, namely specific memory association for an odor, and individual differences in attention to odors were found to influence this odor-induced craving change. In addition, this study found that MVPA techniques are compatible with the unique study design requirements of craving research. Study limitations, implications, and possible future directions are discussed in light of these findings

Zentrale Verarbeitung multimodaler sensorischer Reize nach Stimulation der Nasenschleimhaut mit Nikotin

Zum heutigen Stand der Forschung gibt es, außer der vorliegenden Arbeit, keine funktionellen Kernspinstudien über kortikale Aktivierungen, welche durch Effekte des multimodalen Stimulus Nikotin auf das olfaktorische und das trigeminale System hervorgerufen werden. Appliziert man Nikotindampf in niedrigen Konzentrationen auf die nasale Mukosa, so ruft es Geruchsempfindungen, die durch das olfaktorische System vermittelt werden, hervor. In höheren Konzentrationen ruft Nikotin zusätzlich ein Brennen oder Stechen in der Nase hervor, welches durch das trigeminale System vermittelt wird. Das Ziel der vorliegenden Arbeit war, die Hirnaktivierungen nach intranasaler Stimulation von S(-)-Nikotin in niedrigen, olfaktorisch leicht überschwelligen versus hohen, trigeminal leicht überschwelligen Konzentrationen zu vergleichen. Zuerst wurden die individuellen Geruchs- und Schmerzschwellen von Nikotin von jeweils 30 gesunden Gelegenheitsrauchern mittels PC-kontrolliertem Olfaktometer bestimmt. Danach wurden funktionelle Kernspinuntersuchungen mit einem 1,5 Tesla Magnetresonanztomographen während der Applikation von intranasalen Nikotinreizen in olfaktorisch und trigeminal leicht überschwelligen Konzentrationen durchgeführt. Nach den Bildgebungsexperimenten nahm ein Teil der Probanden an einem weiteren Experiment teil. Während dieses Experiments sollten die Probanden die Intensität der olfaktorischen und trigeminalen Wahrnehmung während intranasaler Nikotinstimulation außerhalb des Magnetresonanztomographen bewerten. Dabei wurden die gleichen Stimulationsparadigmen verwendet wie während der Bildgebungsexperimente. Obwohl die subjektive Wahrnehmung von Nikotindampf in niedrigen und hohen Konzentrationen sich deutlich voneinander unterschied, konnten Aktivierungen in nahezu gleichen Hirnarealen in beiden Experimenten gefunden werden. Diese Hirnareale entsprachen Arealen, von denen bekannt ist, dass sie für die olfaktorische Informationsverarbeitung zuständig sind, aber auch Arealen, die spezifisch für die Verarbeitung von schmerzhaften Reizen sind. Die Ergebnisse zeigen, dass sowohl das olfaktorische, als auch das trigeminale System während chemosensorischer Wahrnehmung von Nikotindampf aktiviert werden und dass es nicht möglich ist, olfaktorische von trigeminalen Effekten zu trennen, indem man die Stimuluskonzentration variiert. Die Aktivierungen von olfaktorischen und trigeminalen Arealen nach chemosensorischer Stimulation mit verschiedenen Nikotinkonzentrationen sind weitgehend unabhängig von der wahrgenommenen Intensität der Stimuli.Besides the present study no neuroimaging data are available on cortical activations induced by the effects of the multimodal stimulus nicotine on the olfactory or the trigeminal system. Applied to the nasal mucosa in low concentrations, nicotine vapor evokes odorous sensations (mediated by the olfactory system). At higher concentrations, nicotine vapor produces burning and stinging sensations in the nose (mediated by the trigeminal system). The aim of this study was to compare brain areas activated by intranasal stimulation with S(-)-nicotine vapor in low versus high concentrations using functional magnetic resonance imaging (fMRI). Olfactory detection thresholds and sensory irritation thresholds for nicotine vapor were determined in thirty healthy occasional smokers respectively using a computer-controlled air-dilution olfactometer. Following this, functional magnetic resonance images were acquired using a 1.5T MR scanner with application of concentrations of nicotine vapor just above the individual’s olfactory detection threshold and just above the individual’s sensory irritation threshold. After the scanning sessions a part of the subjects participated in a further session. They were lying outside the MR scanner and were instructed to evaluate the intensity of the olfactory and the trigeminal percept during the stimulation paradigms used before. Although perceptions of nicotine vapor in low and high concentrations completely differed, activations in basically the same brain areas were found in both fMRI experiments. These brain areas correspond to areas known to be activated following olfactory stimulation of the nasal mucosa, as well as areas specific to processing of painful stimuli. These findings indicate that the olfactory and trigeminal systems are both activated during chemosensory perception of nicotine vapor and it is not possible to separate olfactory from trigeminal effects by varying the concentration of the applied nicotine vapor. Brain activation of olfactory and trigeminal areas related to chemosensory stimulation with different concentrations of nicotine vapor is independent of perceptual strength

Nicotine: Molecular and physiological effects of nicotine in central nervous system - A stereospecific chemosensory model suited to analyze nicotine perception, ‘liking’ and sensory induced craving

Die Nikotinabhängigkeit ist von großer Bedeutung für die aktuelle Gesellschaft, weil sie die Nummer eins der vermeidbaren Todesursachen unserer Zeit ist. Viele Mechanismen, die ihr zugrunde liegen, werden in neuerer Zeit auch mit der Pathophysiologie verschiedener psychiatrischer Störungsbilder wie z.B. Morbus Alzheimer oder ADHS in Verbindung gebracht. Nikotinerg-cholinerge Schaltkreise stellen sich außerdem zunehmend als entscheidender Faktor für kognitive Prozesse wie Gedächtnis, Lernen, Aufmerksamkeit und Wahrnehmung heraus. Viele grundlegende Mechanismen sind jedoch nach wie vor unbekannt. Die vorliegende Arbeit beschäftigt sich mit neurophysiologischen und psychophysiologischen Reaktionen von Rauchern, Rauchern im Entzug und Nichtrauchern auf olfaktorische und trigeminale Nikotinreize sowie auf Kontrollsubstanzen. Hierfür wurden die evozierten Antworten mit EEG und funktioneller Magnetresonanztomographie aufgezeichnet und analysiert. Der kombinierte Einsatz verschiedenster Verfahren zur Messung von Reaktionen des menschlichen Gehirns in verschiedenen Zuständen (Rauchen, Nichtrauchen, im Entzug) auf intranasale Reize ist neuartig und liefert neben der Bestätigung bereits vorliegender Ergebnisse eine Reihe neuer Erkenntnisse, die sowohl für die Forschung als auch für die Praxis wertvolle Anregungen geben können.As the number one preventable death cause of our time nicotine dependence is of great importance to today´s society. Many mechanisms underlying nicotine dependence are latterly also linked to the pathophysiology of varying psychiatric diseases such as Alzheimer´s disease or ADHD. Additionally, nicotinic-cholinergic circuits increasingly emerge as a decisive factor for cognitive processes such as memory, learning, attention and perception. However, until now, a lot of basal mechanisms are still unknown. The present study deals with the neurophysiologic and psychophysiologic reactions of smokers, smokers on withdrawal and nonsmokers to olfactory and trigeminal nicotine stimuli as well as control stimuli. For this purpose evoked reactions were recorded and analysed with EEG and functional magnetic resonance imaging. The combined application of different methods of examining reactions of the human brain in different smoking states (smokers, smokers on withdrawal, nonsmokers) to intranasal stimuli is a new and unique approach. In addition to confirming already existing data, the study provides a set of new findings which might also stimulate future research and support clinical practice