Functional Organization of Cerebral Cortex Systems Neuroscience University of Texas Health Sci. Center Graduate School of Biomedical Sciences 2019 Daniel J. Felleman, Ph.D. 7.168 [email protected] Outline Concepts underlying the subdivision of cortex Architectonics Topography: vision, audition, somatic sensation Cortical connections: hierarchical and parallel ‘streams’ Cortical Modules Specializations? Color Faces Objects/Places Actions Attention From monkeys to humans: what do we now know about brain homologies? Martin I Sereno , Roger BH Tootell Figure 2 Folded (left column) and unfolded (right column) reconstructions of the left cerebral cortex of a human, common chimpanzee, and macaque monkey are shown at the same scale. The cortical surface was Current Opinion in Neurobiology Volume 15, Issue 2 2005 135 - 144 http://dx.doi.org/10.1016/j.conb.2005.03.014reconstructed from T1-weighted MRI Global architectonics Principles of cortical lamination How is cortex subdivided? • Architectonics: cyto-, myelo-, chemo-, immuno-, etc. • Topography: retinotopy, somatotopy, tonotopy, movements, etc. • Connections: anterograde and retrograde tracers; cortical streams and hierarchical organization • Functional properties of neurons: single cells, circuits, modules, areas • Functional contributions to behavior: natural and experimental lesions Human Architectonics: Brodmann and von Bonin Nissl Myelin Pigment Architectonics continued: Immuno-labeled neuron types Smi32 is an antibody against a non-phosphorylated neurofilament. CAT301 is an antibody against cat spinal cord that labels large neuron types; specifically magnocellular-dominated pathways in monkeys and man. smi32 CAT301 Area V2 thick stripes Architectonics alone is usually insufficient… Quantitative Architectonics Macaque cortical areas identified by architecture after Felleman and Van Essen Lewis and Van Essen Some of the proposed cortical areas of primates shown on a dorsolateral view of the left cerebral hemisphere. Kaas J H PNAS 2012;109:10655-10660 ©2012 by National Academy of Sciences Motor areas: architectonics How is cortex subdivided? • Architectonics: cyto-, myelo-, chemo-, immuno-, etc. • Topography: retinotopy, somatotopy, tonotopy, movements, etc. • Connections: anterograde and retrograde tracers; cortical streams and hierarchical organization • Functional properties of neurons: single cells, circuits, modules, areas • Functional contributions to behavior: natural and experimental lesions Summary of visuotopic organization and extent of V1 in Galago garnetti. Rosa M G P et al. J Neurophysiol 1997;77:3193-3217 ©1997 by American Physiological Society Lerch et al 2017 Nat. Neurosci Leftmost: the T1-weighted (T1w) image most commonly used for analyzing brain volumes, voxel based morphometry, cortical thickness, etc. Next, from left to right, are quantitative T1 and T2 (qT1 and qT2, respectively) and myelin water fraction (MWF) maps, estimated using the multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) sequence45. Right three images: FA and mean diffusivity (MD), both from diffusion imaging, and (rightmost) a magnetization transfer ratio (MTR) map. These data indicate the types of rich information about brain structure that can be obtained from MRI in a single session. Sample images acquired from the ALSPAC MRI study, which was approved by the North Somerset and South Bristol Research Ethics Committee and the Baycrest Research Ethics Board and conducted in accordance with its guidelines. Informed written consent was obtained from all participants. The inside and outside surfaces of the cortex are extracted based on a mix of tissue classification and deformable model segmentation. Cortical thickness can then be computed based on the distance between the inside surface and outside surface, and surface area computed on either surface (not shown). For the sake of intersubject statistics as well as to aid in segmenting the cortex into constituent lobes, sulci and gyri, the curvature (or, alternately, some measure of sulcal depth or depth potential) is computed on the surface (depth potential on subject) as well as for a model (depth potential on model). Surface-based registration then takes the segmented model and uses it to parcellate the input surface (segmented subject). Sample images obtained from the POND study. Progress in measuring human visual cortex topography over the past 25 years. Topographic Mapping using Traveling Waves BOLD estimates of retinotopic organization in macaque V1 agree with single- unit estimates. The visual stimuli were a series of slowly expanding rings, each containing a collection of flickering squares (160, 163, 164). The stimulus begins as a small spot located at the center of the visual field; the spot becomes an expanding ring that grows to the edge of the stimulus display. As the ring disappears from view, a new spot, starting at the center replaces it. This stimulus causes a traveling wave of neural activity beginning in the foveal representation, several millimeters posterior to the lunate sulcus. Measuring the time course of the BOLD responses at a series of 3- mm radius regions-of-interest, we see that the BOLD response near the foveal representation is phase-advanced compared with the BOLD response measured in the more peripheral representations (graph at right). The phase of the BOLD response measures the visual field eccentricity that most effectively stimulates each cortical location. The most effective visual field eccentricity is indicated by pseudo-coloring the cortical surface according to the inset at the top (adapted from 142). Annu. Rev. Physiol. 2004.66:735-769. fMRI Topographic Mapping of Human V1 DeYoe et al. 1985 fMRI mapping of human visual cortex Human Visual Field Map Clusters Activations of functional tests for motion and shape sensitivity: Functional Localizers used in conjunction with topographic mapping Kolster H et al. J. Neurosci. 2014;34:10168-10191 Functional Organization of Auditory Cortex Dick F et al. J. Neurosci. 2012;32:16095-16105 ©2012 by Society for Neuroscience Functional tonotopic maps of an individual subject with focus on the right hemisphere of the inflated superior temporal lobe. Dick F et al. J. Neurosci. 2012;32:16095-16105 ©2012 by Society for Neuroscience Somatotopy; one homunculus? Microelectrode somatotopic mapping a, Phase-encoded protocol and raw BOLD response in one voxel. Mancini F et al. J. Neurosci. 2012;32:17155-17162 ©2012 by Society for Neuroscience Surface-based average Aδ (laser) and Aβ (air puffs) maps from seven subjects (dorsolateral view). Mancini F et al. J. Neurosci. 2012;32:17155-17162 ©2012 by Society for Neuroscience How is cortex subdivided? • Architectonics: cyto-, myelo-, chemo-, immuno-, etc. • Topography: retinotopy, somatotopy, tonotopy, movements, etc. • Connections: anterograde and retrograde tracers; cortical streams and hierarchical organization • Functional properties of neurons: single cells, circuits, modules, areas • Functional contributions to behavior: natural and experimental lesions Trans-neuronal transport: eye-specific pathways Laminar Patterns Reciprocal Cortico-cortical Connections Monkey Visual Areas and their Interconnections: 1991 Markov et al JCN 2013 Markov et al 2013 Science 342:578. 1) SLN values constrain models of cortical hierarchy, revealing previously unsuspected areal relations; 2) SLN reflects the operation of a combinatorial distance rule acting differentially on sets of connections between areas; 3) Supragranular layers contain highly segregated bottom-up and top-down streams, both of which exhibit point-to-point connectivity. This contrasts with the infragranular layers, which contain diffuse bottom-up and top- down streams; 4) Cell filling of the parent neurons of FF and FB pathways provides further evidence of compartmentalization; 5) FF pathways have higher weights, cross fewer hierarchical levels, and are less numerous than FB pathways. Markov et al 2014 Markov et al 2014 #labeled neurons/all labeled – intrinsic; >-2 strong -2 to -4 moderate < -4 sparse Markov et al 2014 1615 connections 36% NFP; newly found projections 66% connected Markov et al 2014 33% possible unidirectional Markov et al 2014 Intrinsic correlations between a seed region in the PCC and all other voxels in the brain for a single subject during resting fixation. Resting state functional connectivity; slow spontaneous fluctuations in BOLD Task positive areas: Intraparietal sulcus, Frontal eye field (pre-motor), MT+ Task negative areas: Medial prefrontal, Posterior cingulate, and Lateral parietal Fox M D et al. PNAS 2005;102:9673-9678 ©2005 by National Academy of Sciences Population-based z-score maps showing nodes significantly correlated or anti-correlated with six seed regions (small circles). The conjunction map is an average, including only nodes significantly correlated or anti- correlated with five of the six seed regions Fox M D et al. PNAS 2005;102:9673-9678 ©2005 by National Academy of Sciences Two intrinsically defined anti-correlated processing networks in the brain. Fox M D et al. PNAS 2005;102:9673-9678 ©2005 by National Academy of Sciences Spontaneous correlation maps: similarities to task evoked and anatomical connectivity Vincent et al. 2007 Parallel Cortico-cortical Streams: V1-V2 V2-V4 Topographic Organization of Cortical Connections: V2 How is cortex subdivided? • Architectonics: cyto-, myelo-, chemo-, immuno-, etc. • Topography: retinotopy, somatotopy, tonotopy, movements, etc. • Connections: anterograde