The Studies Of The Neural Substrates Of Attention Using Multi-modal Magnetic Resonance Imaging

Attention is a central theme in cognitive science. It refers to both the preparedness for and selection of certain aspects of our physical environment or some ideas in our mind. Because of the limited capacity of the brain to handle information, the appropriate selection of information for processing becomes especially critical in our daily life. With more research tools in neuropsychological and neuroimaging studies becoming available, our understanding of attention is likely to yield innovations in education and cognitive training. Furthermore, the dysfunction of attention has been implicated in a number of neurological and psychiatric disorders, such as deficit/hyperactivity disorder and schizophrenia. Therefore, the studies for the neural basis of attention may bring new insights into the abnormal mechanisms of these diseases.Attention has various dimensions and characteristics. The previous lesion and functional neuroimaging studies have indicated that there were three key subsystems of attention, i.e. alerting, orienting, and executive control. These components of attention network have been shown to differ in their functional anatomy and neurochemical pathways. Briefly, alerting is defined as achieving and maintaining a state of high sensitivity; orienting refers to the selection of sensory information; and executive control is involved with the processing of cognitively incongruent stimuli or conflict. However, the brain functional and anatomical substrates of attention function are still highly debated, mainly due to the inconsistency among the attention models and the variations in the utilized imaging modalities. Therefore, it has become important to distinguish the roles of distinct brain cortical and subcortical regions on attention function. In this thesis, we utilized multi-modal imaging techniques, including task-related functional magnetic resonance imaging (fMRI), magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), to investigate the neural substrates of attention. The findings revealed that the three components of attention were associated with the functional connectivity, cortical thickness and white matter (WM) integrity in distinct brain regions. In conclusion, current research would provide a better understanding for the neural substrates of attention.Part1:Effects of Functional Connectivity on Executive Control of AttentionObjective:Executive control of attention refers to the higher order cognitive processes involved in the self-regulation of behavior, cognition such as memory, language, emotion and motivation. The current study aims to explore the functional connectivity between anterior cingulate cortex (ACC) and other brain regions, such as the dorsolateral prefrontal cortex (DLPFC), during the manipulation of attentional network test (ANT) and its relationship with the behavioral performance.Materials and Methods:The fMRI was used in twenty healthy male subjects of17to20years, with ANT as the paradigm. ANT could isolate three different attention components: alerting, orienting and executive control. Data were preprocessed by SPM. Correlation analysis was conducted between ACC-DLPFC functional connectivity and behavioral scores of ANT.Results:On average, the accuracy of ANT performance was very high (95.4%), indicating that the participants understood the instruction and were able to response reliably. The correlation between executive control effect and overall mean RT was significant (r=0.58; P<0.01). We found no significant correlations between any two items of the three components of attention. Several regions were activated by executive control, i.e., ACC, middle frontal gyrus, superior frontal gyrus, and thalamus. Significant functional connectivity between the dorsal ACC (dACC) with bilateral DLPFC was found. Furthermore, event-related functional connectivity coefficients between left dACC and left DLPFC were negatively associated with the behavioral scores of executive control (r=-0.627; P<0.01), controlled for age, mean reaction time and correct rate. Whole-brain analysis also revealed other attention-related regions, including bilateral supramarginal gurus, supplementary motor area, insula and subcortical nuclei that show functional connectivity with seed regions (especially the left dACC). Conclusion:The behavioral results prove that the alerting, orienting and executive control is independent to each other. Our findings provide new evidence that ACC and DLPFC are functionally connected and such functional connectivity would exhibit an advantageous influence on executive control function of attention, thereby contributing to our understanding of the integrated role of these brain regions in attentional network. Part2:Anatomical Substrates of the Attention Components: Focus on the Posterior Parietal LobeObjective:Both neuropsychological and functional neuroimaging studies have identified that the posterior parietal lobe (PPL) is critical for the attention function. Generally, it is proposed that human PPL is involved in three distinguishing cognitive functions:spatial perception, vision-for-action and visuospatial attention. The taxonomy of alerting, orienting and executive control attention encompasses those parietal functions and integrates different attention components into one complete system. Controversy over the anatomical substrates of attention has highlighted the heterogeneity of this core cognitive operation and emphasized the complicated roles of distinct parietal subregions. Therfore, this part aims to investigate the unique role of distinct parietal cortical subregions and their underlying WM on attention by means of MRI and DTI.Materials and Methods:In this study, we collected both MRI and DTI data in36(22males) normal young participants. The males and females did not differ in mean age (18.4±0.9vs.17.9±0.9years) and education years (8.6±1.2vs.8.5±1.0years). Then we evaluated their attention performance using ANT. The MR images were first processed with the CIVET MRI analysis pipeline (version1.1.9) developed at Montreal Neurological Institute (MNI) to automatically extract and co-register the cortical surfaces for each subject. The DTI data was processed using FSL (University of Oxford, UK). Cortical thickness, surface area and DTI parameters were extracted from predefined PPL subregions using the automated anatomical labelling (AAL) template and correlated with behavioral performance. The AAL template segmented the PPL in each hemisphere into five partitions:superior parietal lobule, inferior parietal lobule, supramarginal gyrus, angular gyrus and precuneus. Tract-based spatial statistics (TBSS) was used for the voxel-wise statistical analysis. At last we performed Probabilistic diffusion tractography (PDT) to identify the WM pathways.Results:Results indicated structure-behavior relationships on multiple levels. First, a link between the cortical thickness and WM integrity of the right inferior parietal regions and orienting performance was observed. Specifically, PDT demonstrated that the integrity of WM connectivity between the bilateral inferior parietal lobules mediated the orienting performance. Second, the scores of executive control were significantly associated with the WM diffusion metrics of the right supramarginal gyrus. Finally, TBSS analysis revealed that alerting performance was significant correlated with the fractional anisotropy of local WM connecting the right thalamus and supplementary motor area. Conclusion:The most significant novelty is the validation of the distinct roles of PPL subregions on the three sub-networks of attention. These findings could yield a more complete understanding of the nature of the PPL contribution to visuospatial attention. Part3:The Asymmetries of White Matter and Their Influences on AttentionObjective:Human brain hemispheres differ in their anatomy and function. Compared with structural MRI measures of WM volume or density, DTI provides more information about WM tissue microstructure and organization. WM asymmetries of the human brain have been well documented using DTI. However, the relationship between WM asymmetry pattern and cognitive performance is poorly understood because of the limitations of the applied techniques. So the main purpose of this study is to assess the effects of DTI asymmetries on individual differences in attention performances.Materials and Methods:A total of59healthy young subjects (31males) aged15～19years were included in the study. A version of the ANT was adapted as the cognitive task. DTI was performed for each of the subject and the DTI data was processed using FSL. We then used TBSS to test the asymmetries of fiber tracts. To implement the inter-hemispheric comparison of fibers, the4D DTI symmetric skeleton dataset was left-right flipped, and the voxel-wise difference map between the original and flipped images was created. The nonparametric1-sample t-test for the difference map was performed by Randomise program in the FSL, to determine the WM skeleton regions showing significant asymmetries. Finally we tested the correlations between WM integrity/asymmetries and three distinct components of attention, namely alerting, orienting, and executive control.Results:We revealed a number of WM anisotropy asymmetries, including leftward asymmetry of cingulum, corticospinal tract and cerebral peduncle, rightward asymmetry of internal capsule, superior longitudinal fasciculus and posterior corona radiata, as well as heterogeneous asymmetries in anterior corpus callosum and anterior corona radiata (ACR). Moreover, specific correlation was found between asymmetric pattern of inferior frontal ACR and executive control performance. Further tractography from correlated regions generated sagittal fiber paths, which exactly overlapped with inferior fronto-occipital fasciculus (IFOF). The reductions of WM integrity in IFOF are associated with deficits of executive function in patients with first-episode psychosis or chronic trauma. Additionally, current study also proposed that there were no significant relationships of WM anisotropy asymmetries to alerting and orienting functions.Conclusion:We used TBSS to investigate WM integrity asymmetries and for the first time to evaluate their relationships to distinct components of attention. There are a number of differences in WM integrity between human brain hemispheres. Specially, the anisotropy asymmetry in inferior frontal ACR plays a crucial role in executive control function. We speculate that WM anisotropy symmetry might be crucial for specific cognitive functions, especially the implement of which employs both hemispheres.