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Neocortex is known to be histologically organized with respect to depth, and neuronal connections across cortical layers form part of the brain's functional organization[1]. Efferent (outgoing) and afferent (incoming) inter-regional connections are found to originate and terminate at different depths, and this structure relates to the internal/external origin of neuronal activity. Specifically, efferent, inter-regional connections are associated with internally directed, top-down activity; afferent inter-regional connections are associated with bottom-up activity originating from external stimulation. The contribution of top-down and bottom-up neuronal activity to the BOLD signal can perhaps be inferred from depth-related fluctuations in BOLD. By dissociating top-down from bottom-up effects in fMRI, investigators could observe the relative contribution of internally and externally generated activity to the BOLD signal, and potentially test hypotheses regarding the directionality of BOLD connectivity. Previous investigation of depth-dependent BOLD has focused on human visual cortex[2]. In the present work, we have designed an experiment to serve as a proof of principle that (1) depth-dependent BOLD can be measured in higher cortical areas during a language processing task, and (2) that differences in the relative contribution of the BOLD signal at discrete depths, to the total BOLD signal, vary as a function of experimental condition. Data were collected on the Siemens 7T scanner at the Hahn Institute in Essen, Germany. Submillimeter (0.8mm3), T1-weighted data were acquired using MP2RAGE, along with near whole-brain, submillimeter (0.9x0.9x0.943mm x112 slices) 3D-EPI task data. The field of view fully covered bilateral temporal and fusiform regions, but excluded superior brain areas on the order of several centimeters. Participants were presented with an event-related paradigm involving the presentation of words, pseudowords and nonwords in visual and auditory modalities. Only the visual modality is discussed here. Cortical segmentation was performed using FreeSurfer's surface-pipeline. We parcellated the gray matter volume into discrete depths, and the analysis of depth-dependent BOLD was performed with the Laminar Analysis Toolbox (van Mourik). Further analysis was performed using FreeSurfer, AFNI and in-house MATLAB code. Regions included in the depth-dependent analysis were determined by first-level analysis. We have presently collected data from 10 participants. 4 were excluded due to equipment malfunction. In the first-level analysis (volume registration, smoothing, GLM, and significance testing), we observe fusiform activation for Realword>Nonword and Pseudoword>Nonword contrasts. These contrasts additionally show activation along middle temporal gyrus. The depth-dependent analysis was performed on fusiform clusters generated during the first-level analysis. These clusters appeared to show depth-dependent signal differences as a function of experimental condition. We suspect these differences may be related to layer-specific activation and reflect the relative contribution of top-down and bottom-up activity in the observed signal. These are preliminary results, and part of an ongoing effort to establish novel, depth-dependent analysis techniques in higher cortical areas and within the language domain. Future analysis will investigate the nature of the depth-dependent differences and the connectivity profiles of depth-dependent variation among distal cortical regions.[1]DouglasR.J.&MartinK.A.C.(2004).Neuronal Circuits of the Neocortex.Annual Review of Neuroscience,27,419-551.[2]Kok,P.,et al.(2016).Selective Activation of the Deep Layers of the Human Primary Visual Cortex by Top-Down Feedback.Current Biology,26,371-376.
