Theoretical and Clinical Research Based on Functional Magnetic Resonance Brain Imaging Technique
|Keywords||functional MRI object recognition lexical decision auditory inferior frontal gyrus pseudowords Chinese addiction drugdependence heroin craving|
Functional magnetic resonance imaging (fMRI) based on the BOLD (Blood Oxygenation Level Dependent) signal is currently the most widely used neuroimaging technique. Through presenting participants with predefined stimuli, this technique allows observation of the activity in multiple brain areas simultaneously. It combines both functional imaging with anatomical imaging, making it possible to observe mental activity in cognitive and emotional processing in living systems. fMRI is non-invasive, free of radioactive materials, with high spatial/temporal resolution and fast imaging acquisition, relatively less expensive, and can be applied on the same subject multiple times and has become one of the key tools in functional brain imaging. On the one hand, the effective mastering and application of fMRI depend on knowledge of mature design methodology and research approaches for the selection of appropriate experimental variables and setting up of correct experimental tasks and reference control tasks. On the other hand, researchers must take into account the unique response impulse properties of the BOLD signal, understand pros and cons of different design paradigms, such as block design and event-related design and select them properly based on particular research goal. More importantly, researchers must master relatively complicated mathematical, statistical, and computational methods to accurately extract valuable information from massive dataset.To meet these many requirements, this project adopted a first basic research and then clinical research strategy. We first explore in basic cognitive tasks to assure correction understanding and application of thefMRI technique before we apply it on the drug-dependence problem of most interest to us.The cognitive studies include a visual object recognition experiment and a language experiment. The analysis methods are the two most popular software, AFNI and SPM with the first being based in de-convolution and the latter on multiple regression.The object recognition experiment used a block design and explored the main location in brain, which identifies the human face and nature scenes. We scanned nine subjects while they were presented with 3 types of white-black photographs: natural scenery, face, and scrambled nonsense picture. A multiple linear regression was used to identify brain regions responding preferentially to each type of stimulus and common regions for both natural scenery and face. Results revealed two distinct but adjacent regions in both sides of the ventral temporal cortex. Although both regions showed significant activation during both types of stimuli, the medial one more preferentially responded to natural scenery, whereas the lateral one more preferentially responded to face. The general linear test revealed a gradient distribution in that a shift from face-related to scene-related activation was observed from lateral to medial. The results suggest that the boundary between face-associated and scene-associated area is not as clear as previously demonstrated and that the representation of face and scene in the ventral temporal cortex appears to be continuous and overlapped. The results indicate that the strictly localized object representation may not be the most efficient and economical way. More favored is a shared representation where different types of object recognition have weighted usage of component visual processes, such as edge detection, color perception, texture discrimination, contrast analysis, form perception, widely distributed in different brain regions.The language experiment used a fast event-related design to study the lexical processing of pseudowords and real words. Participants did anauditory lexical decision task on a list of randomly intermixed real and pseudo Chinese two-character (or two-syllable) words. Processing of pseudowords and real words activated a highly comparable network of brain regions, including bilateral inferior frontal gyrus, superior, middle temporal gyrus, calcarine and lingual gyrus, and left supramarginal gyrus. Mirroring a behavioral lexical effect, left inferior frontal gyrus (IFG) was significantly more activated for pseudowords than for real words. This result disconfirms a popular view that this area plays a role in grapheme-to-phoneme conversion, as such conversion process was unnecessary in our task with auditory stimulus presentation.Substance abuse is a major health problem with far-reaching social, psychological and physical consequences. In South-east Asia, heroin is the primary drug abused and, in particular, has become the most serious public health problem in China in recent years. Clearly, research on heroin addiction is much needed to better understand its pathophysiology. A high percentage of drug-dependent patients who completed detoxification programs relapse. Relapses are often preceded by craving, which can be described as a strong, persistent desire or sense of compulsion to drug-seeking behaviors, and patients often attribute craving as the cause for their relapses. With a desire for more effective relapse prevention, much attention has been paid to the study of craving, which was typically induced in laboratory settings with drug-related cues. However, as craving is a motivational mental state in highly functioning living systems, it was not until the advance of functional imaging techniques when it is possible to directly investigate its neurobiology in vivo and non-invasively.Using cue-induced craving paradigm, we examined substance specificity of the neural circuitry underlying craving. Following abstinence from water and drug, fourteen heroin addicts underwent scanning during exposure to water-related, drug-related, and neutral cues. Water-related cues elicited anterior cingulate activation, previouslyimplicated for thirst genesis. Drug-related cues activated bilateral inferior frontal cortex (BA 44/45), confirming the critical role of prefrontal cortex in drug craving. Results suggest heroin craving may involve different neural substrates than do desire from basic physiological drives, such as thirst. As the first fMRI study of heroin craving, our study adds to the scant but much-needed brain imaging literature on heroin addiction.The present project, with its series of functional MRI experiments, has made valuable contributions to basic research on visual perception and linguistic lexical processing and to clinical research on heroin drug dependence. It establishes a good basis for future research with fMRI to compare the addiction mechanisms in higher primates (such as monkey) and humans.