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

Rosa M G P et al. J Neurophysiol 1997;77:3193-3217

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

Dick F et al. J. Neurosci. 2012;32:16095-16105

Mancini F et al. J. Neurosci. 2012;32:17155-17162

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

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 and retrograde tracers; cortical streams and hierarchical organization • Functional properties of neurons: single cells, circuits, modules, areas, streams • Functional contributions to behavior: natural and experimental lesions Ocular dominance and orientation selectivity Columnar organization of orientation in V1 V1 Functional Architecture: Cortical Modules as Fundamental Building Blocks of Function Two cortical streams?

How many cortical processing streams? Shape from luminance Shape from texture, disparity Shape from color, shading Shape from motion Space from motion Space from disparity Space for action Faces Places Parallel and Convergent Hierarchical Processing and Streams Modular Organization of Area MT fMRI Color Architecture: globs!

Bevil R. Conway , Sebastian Moeller , Doris Y. Tsao Specialized Color Modules in Macaque Extrastriate Cortex Neuron Volume 56, Issue 3 2007 560 - 573 Functional Properties of Color Glob and non-Glob Neurons

Bevil R. Conway , Sebastian Moeller , Doris Y. Tsao

Specialized Color Modules in Macaque Extrastriate Cortex

Neuron Volume 56, Issue 3 2007 560 - 573 http://dx.doi.org/10.1016/j.neuron.2007.10.008 Progression of globs along inferotemporal gyrus

Conway et al 2013 What is represented in IT modules? How does one approach the functional architecture of ‘higher’ (more anterior) visual cortex?

1. Topographic mapping 2. Functional ‘localizer’ 3. What is the ‘real’ function to localize? 4. Multi-criteria mapping—single function 5. Multi-criteria mapping—multiple functions 6. Across species comparisons—what does this tell you? Visual stimuli and analytical methods.

Kolster H et al. J. Neurosci. 2014;34:10168-10191 Schematic representation of the MT/V5 cluster and surrounding regions: high resolution fMRI topography

Kolster H et al. J. Neurosci. 2010;30:9801-9820

Average activities of the nine cortical areas (color code) in the functional tests: motion localizer (A), shape localizer (B, C), action test (D, E), and three- ©2010 by Society for Neuroscience dimensional shape from motion test (F).

Face-selective representations in monkey temporal cortex.

Pinsk M A et al. J Neurophysiol 2009;101:2581-2600

©2009 by American Physiological Society Face-selective regions in the left and right temporal lobes of 2 humans, superimposed on flattened cortical surfaces (A and B) and a ventral view of the inflated hemispheres (C).

Face-selective regions in 2 macaques

Pinsk M A et al. J Neurophysiol 2009;101:2581-2600

Consistency of fine spatial details in independent group averages

Glasser et al. A multi-modal parcellation of human cerebral cortex. Nature 536: 171-178.

“180 areas bounded by sharp changes in cortical architecture, function, connectivity, and/or Topography…in a group of 210 health young adults” 97 new areas, and 83 previously reported using post-mortem microscopy. Identified using a machineM F Glasser learninget al. classifier Nature 1–8 (2016) doi:10.1038/nature18933 Human Connectome Project Relative myelin content maps (left hemisphere) and task fMRI contrast beta maps from the LANGUAGE story contrast (right hemisphere) on inflated (columns 1 and 3) and flattened surfaces (columns 2 and 4). Rows 1 and 2 are the group averages of the 210P and 210V data sets, respectively. White and black arrows indicate consistent variations in myelin content within primary somatosensory cortex that are correlated with somatotopy (see Supplementary Neuroanatomical Results 6 and Supplementary Neuroanatomical Results Fig. 8). The white oval indicates a small, sharp, and reproducible feature in the right hemisphere of the LANGUAGE story contrast. Relative myelin content will hereafter be referred to as myelin (see legend of Supplementary Fig. 1 in Supplementary Results and Discussion 1.1). Data at http://balsa.wustl.edu/WDpX Parcellation of exemplar area 55b using multi-modal information

The border of 55b is indicated by a white or black outline. a, Myelin map. b, Group average beta map from the LANGUAGE Story versus Baseline task contrast. c, d, Functional connectivity correlation maps from a seed in area PSL (white sphere, arrow) (c) and a seed in area LIPv (white sphere, arrow) (d). e, Gradient magnitude of the myelin map shown in a. f, Gradient magnitude of the LANGUAGE Story versus Baseline task contrast shown in b. g, Mean gradient magnitude of the functional connectivity dense connectome (see section on modalities for parcellation in the Methods). h, A dorsal schematic view of the prefrontal cortex as parcellated inMref F Glasser. 22, inet whichal. Natureshading1–8 (2016)indicates doi:10.1038/nature18933the amount of myelin found using histological stains of cortical grey matter. Data at http://balsa.wustl.edu/Qv4P. The HCP’s multi-modal parcellation, version 1.0 (HCP_MMP1.0)

The 180 areas delineated and identified in both left and right hemispheres are displayed on inflated and flattened cortical surfaces. Black outlines indicate areal borders. Colours indicate the extent to which the areas are associated in the resting state with auditory (red), somatosensory (green), visual (blue), task positive (towards white), or task negative (towards black) groups of areas (see Supplementary Methods 5.4). The legend on the bottom right illustrates the 3D colour space used in the figure. Data at http://balsa.wustl.edu/WN56. M F Glasser et al. Nature 1–8 (2016) doi:10.1038/nature18933 Example parcellated analyses using the HCP’s multi-modal cortical parcellation

a, Dense myelin maps on lateral (top) and medial (bottom) views of inflated left hemisphere. b, c, Example dense (b) and parcellated (c) task fMRI analysis (LANGUAGE story versus baseline) expressed as Z statistic values. d, The entire HCP task fMRI battery’s Z statistics for 86 contrasts (47 unique, see section on modalities for parcellation in the Methods) analysed in parcellated form and displayed as a matrix (rows are parcels, columns are contrasts, white outline indicates the map in c). e, A major improvement in Z statistics from fitting task designs on parcellated time series instead of fitting them on dense time series and then parcellating afterwards (blue points are 360 parcels × 86 task contrasts; note the upward tilting deviation from the red line). f, Parcellated myelin maps. g, A parcellated folding-corrected cortical thickness map (in mm). h, i, Parcellated functional connectivity maps on the brain (seeded from area PGi, black dot). These parcellated connectomes areM computedF Glasser etusing al. Natureeither1–8full (2016)or partial doi:10.1038/nature18933correlation (see Supplementary Methods 7.1). In both cases, the task negative (default mode) network is apparent. j, A parcellated connectome matrix view with the full correlation connectome below and the partial correlation connectome above the diagonal (white line shows the displayed partial correlation brain map). Data at http://balsa.wustl.edu/RG0x.