Systems Neuroscience

GSBS

2019

Inter-areal Pathways

Daniel J. Felleman, Ph.D.

x5629

daniel.felleman@uth.tmc.edu

Overview

• Rat visual cortex: V1 projections: topography and identification of areas

• Macaque visual cortex: laminar patterns, hierarchy, SLN, FLN, NFP

• Macaque cortex: connectome

• Human and macaque intrinsic network architecture: spatial and temporal

correlations

• Functional significance of multiple feedforward inputs to MT

• Specificity of V1 connections

• Specificity and functional significance of V2 to V1 feedback

• Functional significance of feedback circuits from V1 to LGN

Rat Visual Cortex Summary

Identification of Rat Extrastriate Cortical Areas from

V1 Projections

callosal

Visual System : Monkey Visual Areas and their

Interconnections

1) SLN values constrain models of cortical hierarchy, revealing previously unsuspected

areal relations; This reflects the operation of a combinatorial distance rule acting differentially on

sets of connections between areas;

2) 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;

3) FF pathways have higher weights, cross fewer hierarchical levels, and are less numerous than

FB pathways.

Markov et al JCN 2013

Surface atlas 3D reconstruction.

Markov N T et al. Cereb. Cortex 2012;cercor.bhs270© The Author 2012. Published by Oxford University Press.

Cortical surface maps for the F2 exemplar injection.

Markov N T et al. Cereb. Cortex 2012;cercor.bhs270

© The Author 2012. Published by Oxford University Press.

Weight comparisons for known projections and NFP. Distribution of known projections and

NFP as a function of projection magnitude (FLNe) at intervals of 0.5 log10, following the

injection of the 29 target areas.

Markov N T et al. Cereb. Cortex 2012;cercor.bhs270© The Author 2012. Published by Oxford University Press.

Weighted connectivity matrix.

Markov N T et al. Cereb. Cortex 2012;cercor.bhs270

29 x 29 sub-graph91 source x 29 target

In-degree distribution

Markov N T et al. Cereb. Cortex 2012;cercor.bhs270

© The Author 2012. Published by Oxford University Press.

Intrinsic correlations between a seed region in the PCC and all other voxels in

the brain for a single subject during resting fixation.

Fox M D et al. PNAS 2005;102:9673-9678

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

Population-based z-score maps showing nodes significantly correlated or

anticorrelated with six seed regions

Fox M D et al. PNAS 2005;102:9673-9678©2005 by National Academy of Sciences

Fig. 2. Population-based z-score

maps showing nodes significantly

correlated or anticorrelated with six

seed regions (small circles). (Upper)

(Left) Results from three task-

negative seed regions: MPF, PCC,

and LP. (Right) Results from three

task-positive seed regions: IPS,

FEF, and MT. (Lower) The

conjunction map is an average,

including only nodes significantly

correlated or anticorrelated with five

of the six seed regions. White

contours are drawn on the

conjunction map and copied onto

the other maps to facilitate

comparison.

Table 1. Peak foci for intrinsically defined anticorrelated networksBrodmann’s areas Common names Talairach coordinates

The task-positive network

7 IPS (23, 66, 46) (25, 58, 52)

740 Inferior parietal lobule (42, 44, 49) (47, 37, 52)

19 Orbital gyrus (vIPS) (26, 80, 26) (35, 81, 29)

6 FEF (SPrCeS) (24, 12, 61) (28, 7, 54)

6 Inferior precentral sulcus (54, 0, 35)

632 SMApre-SMA (2, 1, 51)

46 DLPFC (40, 39, 26) (38, 41, 22)

1937 MT (47, 69, 3) (54, 63, 8)

Insulafrontal operculum (45, 5, 8) (45, 4, 14)

The task-negative network

31 PCC (2, 36, 37)

30 Retro-splenial (3, 51, 8)

39 LP (47, 67, 36) (53, 67, 36)

3210 MPF (3, 39, 2) (1, 54, 21)

8 Superior frontal (14, 38, 52) (17, 37, 52)

2021 Inferior temporal (61, 33, 15) (65, 17, 15)

35 Parahippocampal gyrus (22, 26, 16) (25, 26, 14)

Cerebellar tonsils (7, 52, 44)

vIPS, ventral intraparietal sulcus; SPreCes, superior precentral sulcus; DLPFC, dorsal

lateral prefrontal cortex.

Two intrinsically defined anticorrelated processing networks in the

brain.

Fox M D et al. PNAS 2005;102:9673-9678

©2005 by National Academy of Sciences

Vincent et al. 2007

Spontaneous correlation maps: similarities to task evoked and anatomical

connectivity

Three visual components from a 21-dimensional spatial ICA decomposition of the complete

dataset, as well as three components from the 21-dimensional TFM analysis.

Smith S M et al. PNAS 2012;109:3131-3136©2012 by National Academy of Sciences

Human temporally-independent functional modes of

spontaneous activity

Spatial maps for TFMs 11 (semantic with default mode system) and 13 (language versus

default mode system).

Smith S M et al. PNAS 2012;109:3131-3136©2012 by National Academy of Sciences

Parcellation of exemplar area 55b using multi-modal information

M F Glasser et al. Nature 1–8 (2016) doi:10.1038/nature18933

The HCP’s multi-modal parcellation, version 1.0 (HCP_MMP1.0)

M F Glasser et al. Nature 1–8 (2016) doi:10.1038/nature18933

Example parcellated analyses using the HCP’s multi-modal cortical parcellation

M F Glasser et al. Nature 1–8 (2016) doi:10.1038/nature18933

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 are computed using either full or partial

correlation (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.

Specificity and Function of Intrinsic, Feedforward and

Feedback Connections

• V1 intrinsic connections

• Parallel pathways to extrastriate cortex: blobs, stripes and beyond

• Functional significance of multiple inputs to area MT

• V1 feedback to LGN

• Functions of cortico-cortical feedback projections

• Orientation and axis specificity of V2 to V1 projections

V1 Intrinsic Connections

Layering and clustering of

horizontal intrinsic

connections in V1

Orientation Specificity

Developmental Refinement

Development of Intrinsic Cortical Circuits

Parallel Thalamo-Cortical-Cortical Pathways

Multiple pathways to Area MT: Significance of

Parallel-Convergent Feedforward Connections

Reversible cooling of V2/V3 to evaluate differential

contribution to MT motion and disparity processing

Cool V2/V3---no clear influence on MT direction selectivity

Disparity processing is disrupted with V2/V3 cooling

Overview of V1 feedback to LGN

Cudeiro and Sillito 2006

Experimental Paradigm: V1 to LGN feedback circuit

Wang et al. 2006

Local application of GABAb

antagonist increases the

activity of V1 layer 6 neurons.

The effect is only revealed with

visual stimulation.

The two LGN cells in B

respond with different shifts in

burst/tonic ratio.

Wang et al. 2006

Phase specificity of V1 L6 to LGN feedback

Overlap of LGN and cortical RFs accounts only for a portion of the effects of cortico-

geniculate activity. In B, green indicates overlapping cells.

The change in burst/tonic ratio (control vs. layer 6 enhancement) is explained by the

phase relationship of lgn to cortical cell; opposite phase leads to decrease in burst/tonic

ration while same phase leads to increase in burst/tonic ratio. Wang et al. 2006

Non-overlapping receptive fields: Most cells that had a change in burst/tonic ratio had

RFs in a plane either parallel or orthogonal to the layer 6 cell’s preferred orientation.

Wang et al. 2006

Overview of V1 feedback to LGN

Cudeiro and Sillito 2006

Metabotropic Glu1 receptors are found on LGN relay cell distal dendrites.

Inhibitory influence of cortico-thalamic signal is mediated by interneurons intrinsic to lgn or in

reticular n. of thalamus.

Effect of mGlu1 blockade is best seen in reduced response to preferred bar length.

With static stimuli, the effect is seen as a reduction in the tonic component, with the burst

unaffected.

Normally, a period of stimulation with high contrast

grating leads to elevation in subsequent responses.

mGlu1 blockade eliminates this effect.

Cudeiro and Sillito 2006

V1 modulation of LGN stimulus-response precision:

Cortical feedback enhances the reliability and structure of visually

evoked responses.

Andolina et al 20072006

Pairs of LGN cells to 3 different oriented gratings and their

correlograms with (above) and without (below) cortical feedback.

Andolina et al 20072006

Summary

• Feedforward pathways are thought to generate the major driving

force in the receptive field properties in the ‘higher’ area.

• Example 1: LGN to V1 simple cells

• Example 2: (not discussed here) V1 to V2;

• Example 3: V1, V2/V3 to MT.

• Feedback pathways are not simple gain control mechanisms of the

afferent pathway.

• Example 4: V1 layer 6 modulation of LGN relay cells---in turn

controls properties of ‘controlling’ cells.

ReferencesAndolina et al. 2007 Corticothalamic feedback enhances stimulus response precision in the

visual system. PNAS 104: 1685-1690.

Cudeiro and Sillito 2006 Looking back: corticothalamic feedback and early visual

processing. TINS 29: 298-306.

Fox, MD et al. 2005 The human brain is intrinsically organized into dynamic, anticorrelated

functional networks. PNAS 102: 9673-9678.

Ichida et al. 2007 Response facilitation from the ‘suppressive’ receptive field surround of

macaque V1 neurons. J Neurophysiol. 98: 2168-2181.

Markov et al. 2012 Cerebral Cortex

Markov et al 2013 JCN

Markov et al 2014 A weighted and directed interareal connectivity matrix for macaque

cerebral cortex. Cerebral Cortex 24:17-36.

Ponce et al. 2008. Integrating motion and depth via parallel pathways. Nat. Neurosci. 11:

216-221.

*Schwabe et al. 2006 The role of feedback in shaping the extra-classical receptive field of

cortical neurons: a recurrent network model. J. Neuroscience 26: 9117-9129.

*Shmuel et al. 2005 Retinotopic axis specificity and selective clustering of feedback

projections from V2 to V1 in the owl monkey. J Neurosci. 25: 2117-2131.

Smith S.M. et al. 2012 Temporally-independent functional modes of spontaneous brain

activity. PNAS 109: 3131-3136.

Vincent JL et al. 2007 Intrinsic functional architecture in the anesthetized monkey brain.

Nature 447: 83-86.

Wang et al. 2006 Functional alignment of feedback effects from visual cortex to thalamus.

Nature Neurosci. 9: 1330-1336.

A mesoscale connectome of the mouse brain: SeungWook Oh, et al., NATURE 508: p.207: 2014

Layering and clustering of feedback projections.

Clustered projections were found in layers 2, 3A, and

5/6. No clusters were found in layer 4.

Analysis of V2 to V1 Feedback Projection Patterns

Correspondence between injection site preferred orientation and

orientation preference of axonal feedback projection fields.

Orientation

preference of

feedback

projections

60% of feedback clusters

were located within 45

degrees of injection site.

In contrast,~70% of

intrinsic horizontal

connections link neurons

within 45 degrees of

injection site.

Axial specificity of feedback

projections. The orientation of

the projection field in V1 largely

extends in the orientation of the

V2 injection site.